RESUMO
BACKGROUND: Islet transplantation offers an effective treatment for selected people with type 1 diabetes and intractable hypoglycaemia. Long-term experience, however, remains limited. We report outcomes from a single-centre cohort up to 20 years after islet transplantation. METHODS: This cohort study included patients older than 18 years with type 1 diabetes undergoing allogeneic islet transplantation between March 11, 1999, and Oct 1, 2019, at the University of Alberta Hospital (Edmonton, AB, Canada). Patients who underwent islet-after-kidney transplantation and islet transplantation alone or islet transplantation before whole-pancreas transplantation (follow-up was censored at the time of whole-pancreas transplantation) were included. Patient survival, graft survival (fasting plasma C-peptide >0·1 nmol/L), insulin independence, glycaemic control, and adverse events are reported. To identify factors associated with prolonged graft survival, recipients with sustained graft survival (≥90% of patient follow-up duration) were compared with those who had non-sustained graft survival (<90% of follow-up duration). Multivariate binary logistic regression analyses were done to determine predictors of sustained graft survival. FINDINGS: Between March 11, 1999, and Oct 1, 2019, 255 patients underwent islet transplantation and were included in the analyses (149 [58%] were female and 218 [85%] were White). Over a median follow-up of 7·4 years (IQR 4·4-12·2), 230 (90%) patients survived. Median graft survival was 5·9 years (IQR 3·0-9·5), and graft failure occurred in 91 (36%) patients. 178 (70%) recipients had sustained graft survival, and 77 (30%) had non-sustained graft survival. At baseline, compared with patients with non-sustained graft survival, those with sustained graft survival had longer median type 1 diabetes duration (33·5 years [IQR 24·3-41·7] vs 26·2 years [17·0-35·5]; p=0·0003), median older age (49·4 years [43·5-56·1] vs 44·2 years [35·4-54·2]; p=0·0011), and lower median insulin requirements (0·53 units/kg per day [0·45-0·67] vs 0·59 units/kg per day [0·48-0·70]; p=0·032), but median HbA1c concentrations were similar (8·2% [7·5-9·0] vs 8·5% [7·8-9·2]; p=0·23). 201 (79%) recipients had insulin independence, with a Kaplan-Meier estimate of 61% (95% CI 54-67) at 1 year, 32% (25-39) at 5 years, 20% (14-27) at 10 years, 11% (6-18) at 15 years, and 8% (2-17) at 20 years. Patients with sustained graft survival had significantly higher rates of insulin independence (160 [90%] of 178 vs 41 [53%] of 77; p<0·0001) and sustained improvements in glycaemic control mixed-main-effects model group effect, p<0·0001) compared with those with non-sustained graft survival. Multivariate analyses identified the combined use of anakinra plus etanercept (adjusted odds ratio 7·5 [95% CI 2·7-21·0], p<0·0001) and the BETA-2 score of 15 or higher (4·1 [1·5-11·4], p=0·0066) as factors associated with sustained graft survival. In recipients with sustained graft survival, the incidence of procedural complications was lower (23 [5%] of 443 infusions vs 17 [10%] of 167 infusions; p=0·027), whereas the incidence of cancer was higher (29 of [16%] of 178 vs four [5%] of 77; p=0·015) than in those with non-sustained graft survival; most were skin cancers (22 [67%] of 33). End-stage renal disease and severe infections were similar between groups. INTERPRETATION: We present the largest single-centre cohort study of long-term outcomes following islet transplantation. Although some limitations with our study remain, such as the retrospective component, a relatively small sample size, and the absence of non-transplant controls, we found that the combined use of anakinra plus etanercept and the BETA-2 score were associated with improved outcomes, and therefore these factors could inform clinical practice. FUNDING: None.
Assuntos
Diabetes Mellitus Tipo 1 , Transplante das Ilhotas Pancreáticas , Estudos de Coortes , Diabetes Mellitus Tipo 1/cirurgia , Etanercepte/uso terapêutico , Feminino , Sobrevivência de Enxerto , Humanos , Insulina/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIMS: To examine the association between dysglycaemia and multiple modifiable factors measured during pregnancy. METHODS: The Healthy Start Study collected self-reported data on modifiable factors in early and mid-pregnancy (median 17 and 27 weeks gestation, respectively) from 832 women. Women received one point for each modifiable factor for which they had optimum scores: diet quality (Healthy Eating Index score ≥64), physical activity level (estimated energy expenditure ≥170 metabolic equivalent task-h/week), and mental health status (Perceived Stress Scale score <6 and Edinburgh Postnatal Depression Scale score <13). Dysglycaemia during pregnancy was defined as an abnormal glucose challenge result, ≥1 abnormal results on an oral glucose tolerance test, or a clinical diagnosis of gestational diabetes. Logistic regression models estimated odds ratios for dysglycaemia as a function of each factor and the total score, adjusted for age, race/ethnicity, pre-pregnancy BMI, history of gestational diabetes, and family history of Type 2 diabetes. RESULTS: In individual analyses, only physical activity was significantly associated with a reduced risk of dysglycaemia (adjusted odds ratio 0.67, 95% CI 0.44-1.00). We observed a significant, dose-response association between increasing numbers of optimal factors and odds of dysglycaemia (adjusted P=0.01). Compared with having no optimal modifiable factors, having all three was associated with a 73% reduced risk of dysglycaemia (adjusted odds ratio 0.27, 95% CI 0.08-0.95). CONCLUSIONS: An increasing number of positive modifiable factors in pregnancy was associated with a dose-response reduction in risk of dysglycaemia. Our results support the hypothesis that modifiable factors in pregnancy are associated with the risk of prenatal dysglycaemia.
Assuntos
Dieta Saudável , Exercício Físico , Transtornos do Metabolismo de Glucose/prevenção & controle , Estilo de Vida Saudável , Doenças do Recém-Nascido/prevenção & controle , Saúde Mental , Complicações na Gravidez/prevenção & controle , Adulto , Estudos de Coortes , Colorado/epidemiologia , Feminino , Transtornos do Metabolismo de Glucose/epidemiologia , Humanos , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Complicações na Gravidez/epidemiologia , Estudos Prospectivos , Risco , Autorrelato , Adulto JovemRESUMO
Continuous summit-to-sea maps showing both land features and shallow-water coral reefs have been completed in Puerto Rico and the U.S. Virgin Islands, using circa 2000 Landsat 7 Enhanced Thematic Mapper (ETM+) Imagery. Continuous land/sea terrain was mapped by merging Digital Elevation Models (DEM) with satellite-derived bathymetry. Benthic habitat characterizations were created by unsupervised classifications of Landsat imagery clustered using field data, and produced maps with an estimated overall accuracy of>75% (Tau coefficient >0.65). These were merged with Geocover-LC (land use/land cover) data to create continuous land/ sea cover maps. Image pairs from different dates were analyzed using Principle Components Analysis (PCA) in order to detect areas of change in the marine environment over two different time intervals: 2000 to 2001, and 1991 to 2003. This activity demonstrates the capabilities of Landsat imagery to produce continuous summit-to-sea maps, as well as detect certain changes in the shallow-water marine environment, providing a valuable tool for efficient coastal zone monitoring and effective management and conservation
Assuntos
Animais , Adaptação Biológica , Antozoários/crescimento & desenvolvimento , Conservação dos Recursos Naturais , Ecossistema , Monitoramento Ambiental/métodos , Comunicações Via Satélite/normas , Altitude , Geologia , Aumento da Imagem/métodos , Imageamento Tridimensional/métodos , Análise de Componente PrincipalRESUMO
Continuous summit-to-sea maps showing both land features and shallow-water coral reefs have been completed in Puerto Rico and the U.S. Virgin Islands, using circa 2000 Landsat 7 Enhanced Thematic Mapper (ETM+) Imagery. Continuous land/sea terrain was mapped by merging Digital Elevation Models (DEM) with satellite-derived bathymetry. Benthic habitat characterizations were created by unsupervised classifications of Landsat imagery clustered using field data, and produced maps with an estimated overall accuracy of>75% (Tau coefficient >0.65). These were merged with Geocover-LC (land use/land cover) data to create continuous land/ sea cover maps. Image pairs from different dates were analyzed using Principle Components Analysis (PCA) in order to detect areas of change in the marine environment over two different time intervals: 2000 to 2001, and 1991 to 2003. This activity demonstrates the capabilities of Landsat imagery to produce continuous summit-to-sea maps, as well as detect certain changes in the shallow-water marine environment, providing a valuable tool for efficient coastal zone monitoring and effective management and conservation.
Assuntos
Adaptação Biológica , Antozoários/crescimento & desenvolvimento , Conservação dos Recursos Naturais , Ecossistema , Monitoramento Ambiental/métodos , Comunicações Via Satélite/normas , Altitude , Animais , Fenômenos Geológicos , Geologia , Aumento da Imagem/métodos , Imageamento Tridimensional/métodos , Análise de Componente Principal , Porto Rico , Ilhas Virgens AmericanasRESUMO
As part of the Hemophilia Growth and Development Study, we investigated the impact of human immunodeficiency virus (HIV) infection on statural growth, weight gain, and skeletal and sexual maturity in more than 300 boys with moderate to severe hemophilia, of whom 62% were infected with HIV. Age-adjusted height and weight were reduced in the HIV-infected subjects (p < 0.001). However, mean weight for height and triceps skin-fold thickness of the infected-boys closely resembled those of the uninfected group. In HIV-infected boys, height for age was positively related to the CD4+ lymphocyte count when the count was < 200 cells/mm3. Age-adjusted serum testosterone levels did not differ by HIV status, but in the infected participants the mean age-adjusted bone age was significantly reduced (p = 0.038) and the distribution of Tanner stages, adjusted for age, differed significantly (p = 0.003). The probability of advancing one or more Tanner stages in the first study year was significantly slowed in HIV-infected boys more than 14 years of age (p = 0.0003). We conclude that linear growth was significantly impaired in boys with hemophilia and HIV infection, but the wasting of malnutrition was not found. The delays in bone age and pubertal maturation strongly suggest that part of the growth failure seen in acquired immunodeficiency syndrome can be attributed to pubertal delay. We speculate that the lack of demonstrable difference in age-adjusted testosterone concentrations might reflect subtle differences in the pattern of secretion of testosterone or in the concentration of sex-hormone binding globulin.
Assuntos
Infecções por HIV/fisiopatologia , Hemofilia A/fisiopatologia , Puberdade Tardia/fisiopatologia , Adolescente , Adulto , Estatura , Peso Corporal , Criança , Infecções por HIV/sangue , Infecções por HIV/complicações , Hemofilia A/sangue , Hemofilia A/complicações , Humanos , Estudos Longitudinais , Masculino , Maturidade Sexual , Testosterona/sangueRESUMO
Endoscopic sinus surgery has been reported to be successful, but lack of a standardized classification system hampers comparison of results between studies, and long-term results of surgery have not been reported in a series of consecutive patients. The results of our first 100 endoscopic sinus surgery procedures, reported previously after an average 9-month follow-up, were reviewed with the application of a new classification scheme and in light of a longer (4-year) follow-up. Surgery was successful in all patients whose sinus symptoms resulted from anatomical variations or suppurative infection, but failed in some patients with hyperplastic disease or polyps. In addition, the presence of reactive airway disease or the acetylsalicylic acid (ASA) triad was a bad prognostic sign. The overall success of the procedure in relieving sinus symptoms decreased from 98% at early follow-up to 91% at 4-year follow-up. Sixty-six percent were successful after one procedure and 25% required more than one procedure to achieve success. The decline in success since our first report in 1990 was mostly attributable to late failure in patients with recurrent symptomatic polyposis. Because symptoms may not recur in these patients for up to 3 years, long-term results of surgery for this disorder are necessary. Symptoms of recurrent polyposis can be controlled medically or by revision surgery.
Assuntos
Endoscopia , Seios Paranasais/cirurgia , Seguimentos , Humanos , Doenças dos Seios Paranasais/patologia , Doenças dos Seios Paranasais/cirurgia , ReoperaçãoRESUMO
A retrospective study was undertaken to analyze the effects of various patient factors on therapy and its outcome in elderly hypertensive subjects. Two hundred and three male hypertensives with a mean age of 63.1 years at entry, were followed in a special hypertension clinic by nurse practitioners under physician supervision, for 2 years or more (mean 3.7 years). Good patient compliance (84%) and blood pressure (BP) reduction were achieved and these were enhanced by advancing age. Neither excessive weight, nor widespread atherosclerosis seemed to interfere with BP control. However, while diastolic BP was well controlled with antihypertensive therapy, systolic BP tended to remain higher than 160 mm Hg in many of the older and more atherosclerotic subjects. Pharmacological treatment did not prevent a gradual although modest deterioration of renal function, which was related to both age and hypertension, and represents a greater problem in black patients. Because of the limitations of such a retrospective study, its conclusions may not be extrapolated for treatment of hypertension in all the elderly.
Assuntos
Hipertensão/tratamento farmacológico , Negro ou Afro-Americano , Fatores Etários , Idoso , Anti-Hipertensivos/efeitos adversos , Arteriosclerose/complicações , População Negra , Peso Corporal , Creatinina/sangue , Humanos , Hipertensão/etnologia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Prognóstico , Estudos Retrospectivos , População BrancaRESUMO
The prevalence of vitamin K deficiency in newborn infants and the influence of perinatal risk factors were studied prospectively in 934 infants. A noncarboxylated prothrombin assay to detect proteins induced in vitamin K absence (PIVKA-II) was used to determine the presence of vitamin K deficiency; of 934 cord blood samples assayed, 2.9% were positive for PIVKA-II (0.015 to 0.15 U/ml). All infants found to have detectable PIVKA-II were born at term. The number of infants positive for PIVKA-II was greater in the group small for gestational age (7.4%) than in those appropriate (2.7%) or large (3.1%) for gestational age. Nine categories of perinatal risk groups were defined: however, the majority of infants who were PIVKA-II positive (63%) were normal. All infants received prophylactic vitamin K, and no infant with PIVKA-II in the cord sample subsequently had clinical bleeding. In two patients the rate of 50% disappearance of PIVKA-II after vitamin K administration approximated 70 hours. Two PIVKA-II positive patients with active bleeding or disseminated intravascular coagulation had an accelerated disappearance of 20 to 40 hours. The long disappearance time of PIVKA-II in a steady state may allow detection of vitamin K deficiency despite administration of vitamin K. The majority of cases of neonatal vitamin K deficiency occurred in normal newborn infants. Therefore, all infants should receive prophylactic vitamin K at birth.