RESUMEN
OBJECTIVES: We analysed national surveillance typing data of Shigella isolated from adult males with domestically acquired infection (a cohort largely consisting of men who have sex with men (MSM)) to establish whether multiple isolates from the same individual over time represented persistent carriage or re-infection. METHODS: We carried out a retrospective cohort study of adult males diagnosed with Shigella from 2004 to 2018. Median time intervals between multiple isolations of Shigella flexneri and S. sonnei were compared. Analysis of whole genome sequencing data provided strain discrimination at the single nucleotide level and was used to quantify the genetic distance among isolates. Maximum likelihood phylogenies were constructed to determine whether persistent carriage (characterized by multiple isolations of the same strain) or re-infection (characterized by multiple isolations of different strains) was best supported by the phylogenetic analysis. A comparison analysis was carried out using data linked to adult females with domestically acquired shigellosis. RESULTS: The number of men reporting multiple isolations of Shigella species was 165/4733 (3.5%) compared with 31/2423 (1.3%) females (p < 0.001). For isolate pairs from men associated with persistent carriage, the isolation time interval range was 6-176 days (median 23.5; IQR 8-70) and single nucleotide polymorphism (SNP) distance range was 0-7 SNPs (median 0.5; IQR 0-2). For those associated with re-infection, the isolation time interval was 34-2636 days (median 732; IQR 191-1258) and the SNP distance was 10-1462 SNPs (median 120; IQR 29-377). DISCUSSION: Multiple Shigella isolations in individuals with domestically acquired infections was more frequently observed in adult males than in adult females. Following the acute phase of infection, carriage can persist for months, and infection can recur within months, even with strains belonging to the same species and the same serotype. A combination of multiple sexual partners, persistent carriage following the acute phase of infection and evidence of recurrent re-infection is likely to contribute to sustained transmission in this population.
Asunto(s)
Portador Sano/epidemiología , Disentería Bacilar/epidemiología , Reinfección/epidemiología , Shigella/aislamiento & purificación , Adulto , Portador Sano/microbiología , Disentería Bacilar/microbiología , Inglaterra/epidemiología , Femenino , Homosexualidad Masculina , Humanos , Masculino , Filogenia , Polimorfismo de Nucleótido Simple , Reinfección/microbiología , Estudios Retrospectivos , Serogrupo , Minorías Sexuales y de Género , Shigella/clasificación , Shigella/genética , Secuenciación Completa del GenomaRESUMEN
Essentials Fibrin clots are often implicated in the progression of liver fibrosis. Liver fibrosis was induced in transgenic mice with defects in clot formation or stabilization. Liver fibrosis and fibrin(ogen) deposition do not require fibrin polymerization or factor XIIIa. Fibrin(ogen) is an in vivo substrate of tissue transglutaminase in experimental liver fibrosis. SUMMARY: Background Intravascular fibrin clots and extravascular fibrin deposits are often implicated in the progression of liver fibrosis. However, evidence supporting a pathological role of fibrin in hepatic fibrosis is indirect and based largely on studies using anticoagulant drugs that inhibit activation of the coagulation protease thrombin, which has other downstream targets that promote fibrosis. Therefore, the goal of this study was to determine the precise role of fibrin deposits in experimental hepatic fibrosis. Methods Liver fibrosis was induced in mice expressing mutant fibrinogen insensitive to thrombin-mediated proteolysis (i.e. locked in the monomeric form), termed FibAEK mice, and factor XIII A2 subunit-deficient (FXIII-/- ) mice. Female wild-type mice, FXIII-/- mice and homozygous FibAEK mice were challenged with carbon tetrachloride (CCl4 ) twice weekly for 4 weeks or 6 weeks (1 mL kg-1 , intraperitoneal). Results Hepatic injury and fibrosis induced by CCl4 challenge were unaffected by FXIII deficiency or inhibition of thrombin-catalyzed fibrin polymer formation (in FibAEK mice). Surprisingly, hepatic deposition of crosslinked fibrin(ogen) was not reduced in CCl4 -challenged FXIII-/- mice or FibAEK mice as compared with wild-type mice. Rather, deposition of crosslinked hepatic fibrin(ogen) following CCl4 challenge was dramatically reduced in tissue transglutaminase-2 (TGM2)-deficient (TGM2-/- ) mice. However, the reduction in crosslinked fibrin(ogen) in TGM2-/- mice did not affect CCl4 -induced liver fibrosis. Conclusions These results indicate that neither traditional fibrin clots, formed by the thrombin-activated FXIII pathway nor atypical TGM2-crosslinked fibrin(ogen) contribute to experimental CCl4 -induced liver fibrosis. Collectively, the results indicate that liver fibrosis occurs independently of intrahepatic fibrin(ogen) deposition.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Fibrinógeno/metabolismo , Proteínas de Unión al GTP/metabolismo , Cirrosis Hepática Experimental/enzimología , Hígado/enzimología , Transglutaminasas/metabolismo , Animales , Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Factor XIII/genética , Factor XIII/metabolismo , Deficiencia del Factor XIII/enzimología , Deficiencia del Factor XIII/genética , Factor XIIIa/genética , Femenino , Fibrinógeno/genética , Hígado/patología , Cirrosis Hepática Experimental/sangre , Cirrosis Hepática Experimental/inducido químicamente , Cirrosis Hepática Experimental/patología , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína Glutamina Gamma Glutamiltransferasa 2 , Especificidad por SustratoRESUMEN
BACKGROUND: Persons with chronic pain often report problems with cognitive abilities, such as memory or attention. There is limited understanding of whether objective performance is consistent with subjective reports, and how psychological factors contribute. We aimed to investigate these relationships in a group of patients expressing cognitive concerns, and evaluate the utility of self-report tools for pain management settings. METHOD: Participants with chronic pain (n = 41) completed standardized neuropsychological tests, and self-report measures of cognitive functioning, pain, mood and sleep, as part of a broader study investigating cognitive performance in pain. RESULTS: Average neuropsychological test performance was subtly below normative means (within one standard deviation). Twenty-five percent of the sample scored substantially below age-adjusted norms on one or more objective tests. There were moderate-to-large associations between objective performance (e.g. Trail-Making B) and subjective cognitive complaints (e.g. Everyday Memory Questionnaire - Revised), controlling for age and education level. This was moderated by anxiety, such that subjective-objective relationships were particularly strong in those with higher anxiety. Poorer test performance was associated with higher pain intensity and catastrophizing. Subjective-objective cognition relationships remained after controlling for catastrophizing. CONCLUSION: Patients' self-reported cognitive concerns concurred with objectively measured performance, independent of age, education and catastrophizing. Moreover, those with severe anxiety were more accurate in predicting their cognitive performance. The findings highlight some interesting cognition-mood relationships, and suggest that easy-to-administer questionnaires, such as the Everyday Memory Questionnaire - Revised and the Behavior Rating Inventory of Executive Function - Adult Version, may be useful to capture cognitive concerns in clinical settings. SIGNIFICANCE: Cognitive concerns in chronic pain reflected objective neurocognitive performance. This was moderated by anxiety, such that self-reported cognition was more consistent with objective performance in those with high anxiety. Our findings suggest that reported cognitive concerns should be heeded, and self-report measures may be used clinically to facilitate dialogue about cognitive functioning.
Asunto(s)
Dolor Crónico/psicología , Disfunción Cognitiva/psicología , Estrés Psicológico/psicología , Adulto , Afecto , Anciano , Ansiedad/psicología , Atención , Catastrofización/psicología , Cognición , Función Ejecutiva , Femenino , Objetivos , Humanos , Masculino , Memoria , Persona de Mediana Edad , Pruebas Neuropsicológicas , Dimensión del Dolor , Autoinforme , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVES: Shigella sonnei is a globally important diarrhoeal pathogen tracked through the surveillance network PulseNet Latin America and Caribbean (PNLA&C), which participates in PulseNet International. PNLA&C laboratories use common molecular techniques to track pathogens causing foodborne illness. We aimed to demonstrate the possibility and advantages of transitioning to whole genome sequencing (WGS) for surveillance within existing networks across a continent where S. sonnei is endemic. METHODS: We applied WGS to representative archive isolates of S. sonnei (n = 323) from laboratories in nine PNLA&C countries to generate a regional phylogenomic reference for S. sonnei and put this in the global context. We used this reference to contextualise 16 S. sonnei from three Argentinian outbreaks, using locally generated sequence data. Assembled genome sequences were used to predict antimicrobial resistance (AMR) phenotypes and identify AMR determinants. RESULTS: S. sonnei isolates clustered in five Latin American sublineages in the global phylogeny, with many (46%, 149 of 323) belonging to previously undescribed sublineages. Predicted multidrug resistance was common (77%, 249 of 323), and clinically relevant differences in AMR were found among sublineages. The regional overview showed that Argentinian outbreak isolates belonged to distinct sublineages and had different epidemiologic origins. CONCLUSIONS: Latin America contains novel genetic diversity of S. sonnei that is relevant on a global scale and commonly exhibits multidrug resistance. Retrospective passive surveillance with WGS has utility for informing treatment, identifying regionally epidemic sublineages and providing a framework for interpretation of prospective, locally sequenced outbreaks.
Asunto(s)
Disentería Bacilar , Enfermedades Transmitidas por los Alimentos , Shigella sonnei/genética , Región del Caribe/epidemiología , ADN Bacteriano/análisis , ADN Bacteriano/genética , Brotes de Enfermedades/prevención & control , Brotes de Enfermedades/estadística & datos numéricos , Farmacorresistencia Bacteriana , Disentería Bacilar/epidemiología , Disentería Bacilar/microbiología , Enfermedades Transmitidas por los Alimentos/epidemiología , Enfermedades Transmitidas por los Alimentos/microbiología , Humanos , América Latina/epidemiología , Vigilancia en Salud Pública , Estudios Retrospectivos , Shigella sonnei/efectos de los fármacos , Secuenciación Completa del GenomaRESUMEN
Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31-49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.
Asunto(s)
Enfermedades Cardiovasculares , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndrome Metabólico , Aloinjertos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Humanos , Síndrome Metabólico/etiología , Síndrome Metabólico/prevención & control , Guías de Práctica Clínica como AsuntoAsunto(s)
Depresión , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Suicidio , Adolescente , Aloinjertos , Niño , Preescolar , Depresión/diagnóstico , Depresión/etiología , Depresión/psicología , Femenino , Estudios de Seguimiento , Neoplasias Hematológicas/psicología , Neoplasias Hematológicas/terapia , Humanos , Lactante , Masculino , Adulto JovenRESUMEN
Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Tamizaje Masivo , Neoplasias Primarias Secundarias/diagnóstico , Femenino , Humanos , Masculino , Neoplasias Primarias Secundarias/epidemiología , Especificidad de Órganos , Factores de RiesgoRESUMEN
Low bone mineral density (BMD) has been reported in recipients of pediatric hematopoietic cell transplantation (HCT), but it is unclear whether age at HCT has a role. The objective of this cross-sectional study was to determine if patients treated with HCT before the age of 10 years have long-term BMD deficits compared with patients transplanted at an older age and with sibling controls. The study included 151 HCT recipients (87 males), age at study 24.7±8.6 years treated with HCT for hematologic malignancies at age 10.9±6.4 years, and 92 healthy sibling controls (49 males), age at study 22.3±8.0 years. Dual-energy x-ray absorptiometry was performed to measure BMD Z-scores for total body BMD (TBMD), lumbar spine BMD (LBMD) and femoral neck BMD (FNBMD, for subjects î¶20 years at study visit). Patients <10 years at HCT had significantly lower TBMD and FNBMD Z-scores (by 0.5 and 0.8 s.d., respectively) compared with controls (P=0.003 and P=0.0001, respectively) and patients >18 years at HCT (P=0.04 and P=0.004, respectively) at an average of 14 years after HCT. In conclusion, this study identified young age at transplant as an important risk factor for bone deficits in young adulthood, suggesting that efforts to reduce bone loss should focus on this patient population.
Asunto(s)
Absorciometría de Fotón/métodos , Enfermedades Óseas Metabólicas/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Osteoporosis/etiología , Acondicionamiento Pretrasplante/efectos adversos , Adolescente , Adulto , Densidad Ósea , Enfermedades Óseas Metabólicas/diagnóstico por imagen , Niño , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Acondicionamiento Pretrasplante/métodos , Adulto JovenRESUMEN
Bone loss has been observed within the first six months after HCT in both children and adults. While there is some evidence that bone formation may be reduced in children after HCT, it is currently unknown whether bone resorption is increased. The objective of this prospective study was to evaluate changes in markers of bone resorption over the first six months after pediatric HCT. Twenty-six participants (eight females) aged 10.9 ± 3.4 yr entered the study prior to HCT. Bone resorption was measured by urine DPD and PYD, and by plasma NTX and CTX. Seventeen participants who completed day +30 visit and either day +100 or +180 visits were included in the analysis. DPD increased between days +30 and +100 (mean change, 11.3 nmol/nmol creatinine; p = 0.012) and between days +30 and +180 (13.7 nmol/nmol creatinine; p = 0.036). PYD increased between days +30 and +100 (32 nmBCE/L; p = 0.019). CTX increased between baseline and day +100 (5.9 µg/L; p = 0.012). Changes in NTX levels were not statistically significant. This study shows that markers of bone resorption increase in children after HCT, suggesting that increased resorption may be a contributing factor to the pathophysiology of bone loss after pediatric HCT.
Asunto(s)
Biomarcadores/metabolismo , Resorción Ósea , Trasplante de Células Madre Hematopoyéticas/métodos , Adolescente , Anemia Aplásica/terapia , Densidad Ósea , Niño , Anemia de Fanconi/terapia , Femenino , Homeostasis , Humanos , Leucemia/terapia , Linfoma/terapia , Masculino , Osteoporosis/metabolismo , Factores de Tiempo , Resultado del TratamientoRESUMEN
Phylogenetic analyses suggest lyssaviruses, including Rabies virus, originated from bats. However, the role of bats in the maintenance, transmission and evolution of lyssaviruses is poorly understood. A number of genetically diverse lyssaviruses are present in Africa, including Lagos bat virus (LBV). A high seroprevalence of antibodies against LBV was detected in Eidolon helvum bats. Longitudinal seroprevalence and age-specific seroprevalence data were analysed and capture-mark-recapture (CMR) analysis used to follow 98 bats over 18 months. These data demonstrate endemic infection, with evidence of horizontal transmission, and force of infection was estimated for differing age categories. The CMR analysis found survival probabilities of seronegative and seropositive bats were not significantly different. The lack of increased mortality in seropositive animals suggests infection is not causing disease after extended incubation. These key findings point towards acute transmission of bat lyssaviruses in adapted bat hosts that occurs at a far higher rate than the occurrence of disease.
Asunto(s)
Quirópteros/virología , Lyssavirus , Infecciones por Rhabdoviridae/epidemiología , Infecciones por Rhabdoviridae/virología , Factores de Edad , Animales , Anticuerpos Antivirales/sangre , Encéfalo/virología , Quirópteros/sangre , Estudios Transversales , Femenino , Ghana/epidemiología , Estudios Longitudinales , Masculino , Boca/virología , ARN Viral , Infecciones por Rhabdoviridae/veterinaria , Estudios SeroepidemiológicosRESUMEN
Increasing numbers of hematopoietic cell transplantations (HCTs) are being performed annually with a greater number of long-term survivors. There is increasing concern regarding the late complications and long-term effects that are secondary to treatment exposures before HCT as well as during the HCT conditioning therapy. In both the autologous as well as allogeneic transplant setting, transplant survivors experience mortality rates higher than the general population and the risk of premature cardiovascular (CV)-related death is increased 2.3-fold compared with the general population. The etiology of CV-related deaths in HCT survivors is multifactorial; however, increasing evidence suggests that HCT survivors are at higher risk of developing adverse CV risk factors leading to the development of the metabolic syndrome (a constellation high triglyceride levels, low high-density lipoprotein-cholesterol, hypertension, high fasting blood sugars and increased waist circumference), which then predisposes individuals to risk for early CV-related death. Resistance to insulin is the primary underlying pathophysiologic mechanism that contributes to the development of metabolic syndrome and HCT survivors have been shown to be more likely to develop hypertension, hyperlipidemia and to be insulin resistant. However, the relationship between HCT-related treatment exposures (total body irradiation, high dose chemotherapy, calcineurin inhibitors, steroids, etc) and transplant-related complications (such as GVHD) with the development of CV risk factors and insulin resistance is still in the early stages of investigation. Greater knowledge of the concern regarding CV risk in HCT survivors among both patients and care providers will provide the opportunity for appropriate screening as well as interventions for modifiable risk factors.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Síndrome Metabólico/etiología , Adolescente , Adulto , Composición Corporal , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Niño , Femenino , Trasplante de Células Madre Hematopoyéticas/mortalidad , Hormona de Crecimiento Humana/deficiencia , Humanos , Resistencia a la Insulina , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Riesgo , Factores de Riesgo , Vigilancia de Guardia , Sobrevivientes , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Autólogo/efectos adversos , Trasplante Homólogo/efectos adversos , Irradiación Corporal Total/efectos adversosRESUMEN
Patients undergoing hematopoietic cell transplantation (HCT) are at increased risk of chronic health conditions, including second malignant neoplasms and cardiovascular disease. Little is known about health behaviors and cancer screening practices among HCT survivors that could moderate the risk of these conditions. The BM transplant survivor study examined health behaviors and cancer screening practices in individuals who underwent HCT between 1976 and 1998, and survived 2+ years. Health behavior was deemed as high risk, if an individual was a current smoker and if they reported risky alcohol intake (≥4 drinks per day (males), ≥3 drinks per day (females)) on days of alcohol consumption. Cancer screening assessment was per American Cancer Society recommendations. There were 1040 survivors: 42.7% underwent allogeneic HCT; 43.8% were female; median time from HCT: 7.4 years (range 2.0-27.7 years). Median age at study participation: 43.8 years (range 18.3-73.0 years). Multivariate regression analysis revealed younger age (<35 years) at study participation (Odds ratio (OR)=4.7; P<0.01) and lower education (Asunto(s)
Detección Precoz del Cáncer/métodos
, Conductas Relacionadas con la Salud
, Trasplante de Células Madre Hematopoyéticas
, Adolescente
, Adulto
, Anciano
, Trasplante de Médula Ósea
, Femenino
, Humanos
, Masculino
, Persona de Mediana Edad
, Sobrevivientes
, Trasplante Homólogo
, Adulto Joven
RESUMEN
Bats constitute a reservoir of zoonotic infections and some bat paramyxoviruses are capable of cross-species transmission, often with fatal consequences. Determining the level of viral diversity in reservoir populations is fundamental to understanding and predicting viral emergence. This is particularly relevant for RNA viruses where the adaptive mutations required for cross-species transmission can be present in the reservoir host. We report the use of non-invasively collected, pooled, neat urine samples as a robust sample type for investigating paramyxoviruses in bat populations. Using consensus PCR assays we have detected a high incidence and genetic diversity of novel paramyxoviruses in an urban fruit bat population over a short period of time. This may suggest a similarly unique relationship between bats and the members of the family Paramyxoviridae as proposed for some other viral families. Additionally, the high rate of bat-human contact at the study site calls for the zoonotic potential of the detected viruses to be investigated further.
Asunto(s)
Quirópteros/virología , Infecciones por Paramyxoviridae/transmisión , Paramyxovirinae/fisiología , Animales , Secuencia de Bases , Variación Genética/genética , Ghana , Humanos , Datos de Secuencia Molecular , Infecciones por Paramyxoviridae/virología , Paramyxovirinae/genética , Filogenia , Reacción en Cadena de la Polimerasa , Población UrbanaRESUMEN
Little is known about serum vitamin D levels following hematopoietic cell transplantation (HCT). Patients are instructed to avoid sun exposure because of an increased risk of skin cancers. Altered gastrointestinal absorptive capacity as a result of GVHD, bile acid or pancreatic enzyme insufficiency or bacterial overgrowth may lead to difficulty in absorbing the fat-soluble vitamin D. This study was undertaken to determine the prevalence of serum 25-hydroxyvitamin D (25(OH)D) deficiency, and factors associated with 25(OH)D deficiency, among children and adults who were at least 1 year following HCT. A total of 95 participants (54 males and 41 females) completed a questionnaire on usual diet and lifestyle, and provided a blood sample for 25(OH)D determinations between November 2008 and July 2009. The majority of participants had serum 25(OH)D levels ≥75 nmol/L (n=62, 65%), 23 had insufficient levels (50-75 nmol/L) and 10 participants were deficient (<50 nmol/L). The majority of participants reported regular use of vitamin D supplements (n=58, 61%). Prednisone use was significantly inversely associated with serum 25(OH)D concentrations. Total vitamin D intake was the strongest single predictor of 25(OH)D concentrations. These findings suggest that 400-600 IU vitamin D per day appears to be required to achieve optimal serum 25(OH)D concentrations following HCT.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Deficiencia de Vitamina D/etiología , Vitamina D/análogos & derivados , Adolescente , Adulto , Anciano , Índice de Masa Corporal , Niño , Preescolar , Suplementos Dietéticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Prednisona/efectos adversos , Luz Solar , Sobrevivientes , Vitamina D/administración & dosificación , Vitamina D/sangre , Deficiencia de Vitamina D/sangreRESUMEN
Pulmonary cytolytic thrombi (PCT) is an uncommon complication after hematopoietic cell transplantation. Although the pathogenesis is unknown, patients typically respond to systemic corticosteroid treatment. Considering corticosteroids may impair GVL reactions, we reviewed the records of 324 pediatric patients who received a transplant for leukemia and compared the outcomes of those with PCT (n=14) to those without PCT (n=310). PCT patients had a significantly more acute GVHD (aGVHD) and chronic GVHD (cGVHD). Though 3-year non-relapse mortality and OS were similar, there was significantly less relapse in patients with PCT compared to those without PCT (0 vs 28%, P=0.02), regardless of the presence or absence of aGVHD. In multivariate analysis, grade II-IV aGVHD (P=0.02), cGVHD (P=0.01) and development of PCT (P<0.01) were independently associated with less relapse. These data suggest that patients with PCT are at greater risk for GVHD, but at lower risk of leukemia relapse.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia/patología , Leucemia/cirugía , Embolia Pulmonar/etiología , Acondicionamiento Pretrasplante/efectos adversos , Adolescente , Niño , Preescolar , Trasplante de Células Madre de Sangre del Cordón Umbilical , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/patología , Humanos , Leucemia/sangre , Masculino , Análisis Multivariante , Embolia Pulmonar/patología , Recurrencia , Resultado del TratamientoRESUMEN
We retrospectively compared clinical outcomes in 1593 T-replete unrelated donor (URD) marrow transplant recipients with AML, MDS and CML who received myeloablative conditioning regimens of either BU and CY (BuCy), standard-dose Cy/TBI (1000-1260 cGy) or high-dose Cy/TBI (1320-1500 cGy). Subjects were drawn from patients transplanted between 1991 and 1999 facilitated by the National Marrow Donor Program. Patients who received high-dose Cy/TBI regimens were slightly younger, more likely to receive a mismatched transplant and to have intermediate or advanced disease compared with patients in the BuCy or standard-dose TBI group. Neutrophil recovery was significantly higher in the standard-dose CY/TBI group compared with the high-dose Cy/TBI or BuCy group. Patients who received the high-dose Cy/TBI regimen had an increased risk of developing grades III-IV aGVHD when compared with the control group who received BuCy (P = 0.011). OS, disease-free survival (DFS), TRM and relapse were not significantly different between any of the regimens. We conclude that BuCy, standard-dose and high-dose Cy/TBI regimens have equivalent efficacy profiles for OS, DFS, TRM and relapse risk in patients undergoing T-replete URD marrow transplantation for AML, CML and MDS.
Asunto(s)
Trasplante de Médula Ósea , Busulfano/uso terapéutico , Ciclofosfamida/uso terapéutico , Leucemia Mieloide/terapia , Síndromes Mielodisplásicos/terapia , Acondicionamiento Pretrasplante/métodos , Irradiación Corporal Total , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Busulfano/administración & dosificación , Busulfano/efectos adversos , Niño , Preescolar , Terapia Combinada/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Femenino , Humanos , Lactante , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide de Fase Crónica/terapia , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/administración & dosificación , Agonistas Mieloablativos/efectos adversos , Agonistas Mieloablativos/uso terapéutico , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversos , Resultado del Tratamiento , Irradiación Corporal Total/efectos adversos , Adulto JovenRESUMEN
Dyskeratosis congenita (DC) is characterized by reticular skin pigmentation, oral leukoplakia and abnormal nails. Patients with DC have very short telomeres and approximately one-half have mutations in telomere biology genes. A majority of patients with DC develop BM failure (BMF). Hematopoietic cell transplantation (HCT) represents the only known cure for BMF in DC, but poses significant toxicities. We report six patients who underwent allogeneic HCT with a novel nonmyeloablative conditioning regimen specifically designed for DC patients. Graft sources included related PBSCs (1), unrelated BM (2) and unrelated double umbilical cord blood (3). Complete donor engraftment was achieved in five of six patients. One patient had initial autologous hematopoietic recovery, which was followed by a second transplant that resulted in 88% donor chimerism. With a median follow-up of 26.5 months, four patients are alive, three of whom were recipients of unrelated grafts. We conclude with this small study that encouraging short-term survival can be achieved with HCT in patients with DC using a preparative regimen designed to promote donor engraftment and minimize life-threatening disease-specific complications such as pulmonary fibrosis. Long-term follow-up will be crucial with respect to individualized patient care with each of the transplanted individuals.
Asunto(s)
Disqueratosis Congénita/terapia , Trasplante de Células Madre Hematopoyéticas , Acondicionamiento Pretrasplante/métodos , Adolescente , Alemtuzumab , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Anticuerpos Antineoplásicos/administración & dosificación , Anticuerpos Antineoplásicos/efectos adversos , Anticuerpos Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea/efectos adversos , Preescolar , Terapia Combinada/efectos adversos , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Disqueratosis Congénita/fisiopatología , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/prevención & control , Acondicionamiento Pretrasplante/efectos adversos , Vidarabina/administración & dosificación , Vidarabina/efectos adversos , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico , Irradiación Corporal Total/efectos adversos , Adulto JovenRESUMEN
The Bone Marrow Transplant Survivor Study is a retrospective cohort study in which participants who received hematopoietic cell transplantation (HCT) between 1974 and 1998 and survived for î¶2 years completed a 255-item questionnaire on late effects occurring after HCT. There were 281 survivors with acute myeloid leukemia (AML) and 120 with acute lymphoblastic leukemia (ALL). Siblings of participants (n=319) were recruited for comparison. Median age at interview was 36.5 years for survivors and 44 years for siblings. Median follow-up after HCT was 8.4 years. Conditioning included total body irradiation in 86% of AML and 100% of ALL subjects. The frequencies of late effects did not differ between ALL and AML survivors. Compared with siblings, survivors had a higher frequency of diabetes, hypothyroidism, osteoporosis, exercise-induced shortness of breath, neurosensory impairments and problems with balance, tremor or weakness. In multivariable analysis, the risk of these outcomes did not differ by diagnosis. Survivors after allogeneic HCT had higher odds of diabetes (odds ratio (OR)=3.9, P=0.04), osteoporosis (OR=3.1, P=0.05), abnormal sense of touch (OR=2.6, P=0.02) and reported their overall health as fair or poor (OR=2.2, P=0.03). Ongoing surveillance for these late effects and appropriate interventions are required to improve the health status of ALL and AML survivors after HCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sobrevivientes , Adulto , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidadRESUMEN
Since the introduction of imatinib mesylate, the role of allogeneic hematopoietic cell transplantation (allo-HCT) for CML has essentially been reserved for patients with advanced disease or imatinib resistance. In addition, there have been concerns regarding imatinib associated cardiac toxicity. We investigated the outcome of 61 patients with CML who received a myeloablative allo-HCT at the University of Minnesota between 1999 and 2006. The median age at HCT was 38.4 (range; 6.9-56.9) years. Thirty-seven patients were in first chronic phase and twenty-four patients in a second chronic or accelerated phase at the time of HCT. Twenty-six patients received imatinib therapy before or after HCT, and thirty-five patients either never received imatinib (n=32) or received it only at the time of relapse after HCT (n=3). OS and relapse-free survival (RFS) at 2 years was 69 and 55% for the imatinib group, and 57 and 49% for the non-imatinib group (P=0.57 and 0.95, respectively). There was no difference in the risk of relapse at 2 years between the groups. Symptomatic cardiac toxicity at 1 year was reported in three imatinib group (12%) and two non-imatinib group (6%) patients (P=0.44). Thus, patients treated with imatinib either before or after myeloablative allo-HCT had no increase in cardiac toxicity.