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《Genetics in medicine》2020,22(11):1794-1802
PurposeNeurofibromatosis type 1 (NF1) is associated with tumor predisposition and nonmalignant health conditions. Whether survivors of childhood cancer with NF1 are at increased risk for poor long-term health outcomes is unknown.MethodsOne hundred forty-seven 5+ year survivors of childhood glioma with NF1 from the Childhood Cancer Survivor Study were compared with 2629 non-NF1 glioma survivors and 5051 siblings for late mortality, chronic health conditions, and psychosocial, neurocognitive, and socioeconomic outcomes.ResultsSurvivors with NF1 (age at diagnosis: 6.8 ± 4.8 years) had greater cumulative incidence of late mortality 30 years after diagnosis (46.3% [95% confidence interval: 23.9–62.2%]) compared with non-NF1 survivors (18.0% [16.1–20.0%]) and siblings (0.9% [0.6–1.2%]), largely due to subsequent neoplasms. Compared with survivors without NF1, those with NF1 had more severe/life-threatening chronic conditions at cohort entry (46.3% [38.1–54.4%] vs. 30.8% [29.1–32.6%]), but similar rates of new conditions during follow-up (rate ratio: 1.26 [0.90–1.77]). Survivors with NF1 were more likely to report psychosocial impairments, neurocognitive deficits, and socioeconomic difficulties compared with survivors without NF1.ConclusionsLate mortality among glioma survivors with NF1 is twice that of other survivors, due largely to subsequent malignancies. Screening, prevention, and early intervention for chronic health conditions and psychosocial and neurocognitive deficits may reduce long-term morbidity in this vulnerable population. 相似文献
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Study objectiveFibrinogen concentrate is used to treat severe postpartum hemorrhage despite limited evidence of its effectiveness in obstetric settings. We aimed to explore the association between its administration and maternal outcomes in women with severe postpartum hemorrhage.Design, setting and patientsThis secondary analysis of the EPIMOMS prospective population-based study, exploring severe maternal morbidity, as defined by national expert consensus (2012–2013, 182,309 deliveries, France), included all women with severe postpartum hemorrhage and transfused with red blood cells during active bleeding.MeasurementsThe primary endpoint was maternal near-miss or death, and the secondary endpoint the total number of red blood cells units transfused.InterventionsWe studied fibrinogen concentrate administration as a binary variable and then by the timing of its administration. We used multivariable analysis and propensity score matching to account for potential indication bias.Main resultsAmong the 730 women with severe postpartum hemorrhage and transfused, 313 (42.9%) received fibrinogen concentrate, and 142 (19.5%) met near-miss criteria or died. The risk of near-miss or death was not significantly lower among the women treated with fibrinogen concentrate than among those not treated, in either the multivariable analysis (adjusted RR = 1.03; 95% CI, 0.72–1.49; P = 0.855) or the propensity score analysis (RR = 0.85; 95% CI, 0.55–1.32; P = 0.477). Among women treated with fibrinogen concentrate, administration more than three hours after red blood cell transfusion started was associated with a higher risk of near-miss or death than administration before or within 30 min after the transfusion began (adjusted RR = 2.07; 95% CI, 1.10–3.89; P = 0.024). Results were similar for the secondary endpoint.ConclusionsThe use of fibrinogen concentrate in severe postpartum hemorrhage needing red blood cell transfusion during active bleeding is not associated with improved maternal outcomes. 相似文献
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《Clinical Lymphoma, Myeloma & Leukemia》2021,21(8):e666-e673
BackgroundIKZF1 deletions are associated with adverse outcomes in B-cell acute lymphoblastic leukemia (B-ALL). We assessed the prevalence and clinical impact of functional subtypes of IKZF1 deletions in pediatric BCR–ABL1-negative B-ALL. Patients andMethodsThis retrospective study of IKZF1 deletions was done in cases of pediatric BCR–ABL1-negative B-ALL. The genomic DNA of cases, over a 53-month period, was analyzed using multiplex ligation-dependent probe amplification and multiplex fluorescent polymerase chain reaction. The deletions were divided into functional subgroups: (1) loss-of-function/haploinsufficiency, (2) dominant-negative, and (3) a combination of both types of deletion. The post-induction remission status, event-free survival (EFS), and overall survival (OS) were noted.ResultsOut of 320 cases, 47 (14.7%) had IKZF1 deletions. Thirty-six of the 47 (77%) had loss-of-function deletions, 10 (21%) had dominant-negative deletions, and one (2%) had a combination of both types. The post-induction remission rates in cases with loss-of-function deletions (22/30, 73%; P = .060) and dominant-negative deletions (4/5, 80%; P = .517) were lower compared with those without deletions (215/248, 86.7%). These cases also had worse median EFS: 21.1 months (P = .006) for loss-of-function and 15.4 months (P = .156) for dominant-negative deletions, compared with 46.4 months in cases without IKZF1 deletions. They also had worse median OS: 23.4 months (P = .012) for loss-of-function deletions and 15.7 months (P = .233) for dominant-negative deletions, compared with median not reached in cases without IKZF1 deletions.ConclusionThe IKZF1 deletions were seen in 14.7% of BCR–ABL1-negative pediatric B-ALL. Most of these deletions (77%) were loss-of-function type. The cases with loss-of-function deletions had lower remission rates and poor EFS and OS compared with cases without IKZF1 deletions. A similar trend of poor outcome was seen in the few cases with dominant-negative IKZF1 deletions. 相似文献
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《Transplantation proceedings》2019,51(6):1956-1961
BackgroundNew-onset diabetes after transplant is a severe complication that can present in liver transplant recipients, negatively impacting quality of life and graft survival. It also contributes to increased risk of infection, cardiovascular disease, and rejection, which are the main causes of death among liver transplant recipients. The aim of the present study was to assess the risk factors associated with new-onset diabetes after transplant.MethodThis was a case control study based on the data from 146 liver transplant patients at a reference hospital. The data from the charts were collected using a 2-part form: Part I (sociodemographic variables) and Part II (clinical variables).ResultsMultiple analysis showed that pre-existing systemic arterial hypertension (odds ratio [OR], 2.65; 95% CI, 1.12–6.28) and the use of sodium mycophenolate associated with tacrolimus (OR, 2.68; 95% CI, 1.02–7.06) increased the risk of new-onset diabetes after transplant. On comparing the anthropometric variables, lipid panel, and blood glucose levels of liver transplant patients with and without diabetes, higher glycemic levels were found in the group with diabetes (P < .001).ConclusionPre-existing systemic arterial hypertension and the associated use of sodium mycophenolate and tacrolimus increased the risk of new-onset diabetes after transplant. 相似文献
60.
《BONE》2015
Osteoporosis and sarcopenia are common in older age and associated with significant morbidity and mortality. Consequently, they are both attended by a considerable socioeconomic burden. Osteoporosis was defined by the World Health Organisation (WHO) in 1994 as a bone mineral density of less than 2.5 standard deviations below the sex-specific young adult mean and this characterisation has been adopted globally. Subsequently, a further step forward was taken when bone mineral density was incorporated into fracture risk prediction algorithms, such as the Fracture Risk Assessment Tool (FRAX®) also developed by the WHO. In contrast, for sarcopenia there have been several diagnostic criteria suggested, initially relating to low muscle mass alone and more recently low muscle mass and muscle function. However, none of these have been universally accepted. This has led to difficulties in accurately delineating the burden of disease, exploring geographic differences, and recruiting appropriate subjects to clinical trials. There is also uncertainty about how improvement in sarcopenia should be measured in pharmaceutical trials. Reasons for these difficulties include the number of facets of muscle health available, e.g. mass, strength, function, and performance, and the various clinical outcomes to which sarcopenia can be related such as falls, fracture, disability and premature mortality. It is imperative that a universal definition of sarcopenia is reached soon to facilitate greater progress in research into this debilitating condition.This article is part of a Special Issue entitled “Muscle Bone Interactions”. 相似文献