Long-Term Outcomes of Alemtuzumab-Based Reduced-Intensity Conditioned Hematopoietic Stem Cell Transplantation for Myelodysplastic Syndrome and Acute Myelogenous Leukemia Secondary to Myelodysplastic Syndrome

Allogeneic hematopoietic stem cell transplantation (HSCT) with reduced-intensity conditioning (RIC) offers a potential cure for patients with myelodysplastic syndrome (MDS) who are ineligible for standard-intensity regimens. Previously published data from our institution suggest excellent outcomes at 1 yr using a uniform fludarabine, busulfan, and alemtuzumab-based regimen. Here we report long-term follow-up of 192 patients with MDS and acute myelogenous leukemia (AML) secondary to MDS (MDS-AML) transplanted with this protocol, using sibling (n = 45) or matched unrelated (n = 147) donors. The median age of the cohort was 57 yr (range, 21 to 72 yr), and median follow-up was 4.5 yr (range, 0.1 to 10.6 yr). The 5-yr overall survival (OS), event-free survival, and nonrelapse mortality were 44%, 33%, and 26% respectively. The incidence of de novo chronic graft-versus-host disease (GVHD) was low at 19%, illustrating the efficacy of alemtuzumab for GVHD prophylaxis. Conversely, the 5-yr relapse rate was 51%. For younger patients (age <50 yr), the 5-yr OS and relapse rates were 58% and 39%, respectively. On multivariate analysis, advanced age predicted significantly worse outcomes, with patients age >60 yr having a 5-yr OS of 15% and relapse rate of 66%. Patients receiving preemptive donor lymphocyte infusions had an impressive 5-yr OS of 67%, suggesting that this protocol may lend itself to the incorporation of immunotherapeutic strategies. Overall, these data demonstrate good 5-yr OS for patients with MDS and MDS-AML undergoing alemtuzumab-based RIC-HSCT. The low rate of chronic GVHD is encouraging, and comparative studies with other RIC protocols are warranted.     

64层螺旋CT在肿瘤调强放射治疗定位中的应用及分析

目的：探讨64层螺旋CT在肿瘤调强放射治疗定位中的临床应用及CT扫描床的误差分析。方法：收集我院2010年6月-2011年6月在TOSHIBA Aquiiion 64层螺旋CT机上进行肿瘤调强放疗定位CT扫描患者25例。其中，男13例，女10例，年龄35—73岁，平均年龄55岁。头颈部肿瘤10例，胸部肿瘤5例，腹部肿瘤6例，盆腔肿瘤4例。CT定位图像经DICOM3．0接口传输到XVI软件中，在Workstation上进行治疗床与定位床的误差分析。结果：组内数据符合统计学意义（P〈0．05），误差值X轴为（0．968±0．910）°，Y轴为（0．508±2．09）°，Z轴为（0．3±2．62）°。除X轴外，旋转误差均不符合国标GB／T17589—1998。结论：64层螺旋CT碳纤维平板床在肿瘤调强放疗定位中误差已超过阈值，不适合做精确调强放射治疗定位。     

Technical aspects of radiation therapy for anal cancer

Historically treated with surgery, current practice recommends anal carcinoma to be treated with a combination of chemotherapy and radiation. This review will examine the anatomy, modes of disease spread and recurrence, and evaluate the existing evidence for treatment options for these tumors. An in-depth examination of specific radiation therapy (RT) techniques—such as conventional 3D-conformal RT and intensity-modulated RT—will be discussed along with modern dose constraints. RT field arrangement, patient setup, and recommended gross and clinical target volume (CTV) contours will be considered. Areas in need of further investigation, such as the role in treatment for positron emission tomography (PET) will be explored.     

Pain intensity is associated with both performance-based disability and self-reported disability in a sample of older adults attending primary health care centers

BackgroundOlder adults' function level can be used as a predictor of future detrimental events, such as disability, reliance on others, risk of institutionalization and likelihood of death. The assessment of function at the primary health care centers using self-reported and/or performance based measures is of prime importance.ObjectiveTo determine whether personal factors, pain, depression and physical activity are associated with self-reported and performance based disability for older adults aged ≥60 years attending primary health care centers, as measured by the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) and Short Physical Performance Battery (SPPB), respectively.MethodsParticipants (196 females and 55 males; mean age ± SD = 70.87 ± 7.76) had their pain, self-reported disability, performance, physical activity levels and depressive symptoms assessed. Regression analyses were performed with self-reported and performance-based disability as the dependent variable and age, sex, education, chronic conditions, depression, physical activity and pain characteristics as dependent variables.ResultsMean (SD) results for SPPB were 8.45 (2.86) and 20.06 (8.21) for WHODAS. Pain intensity, depression, pain frequency, number of chronic conditions and level of physical activity explained 44% of the self-reported disability variance. Pain intensity, age, level of physical activity, years of formal education and chronic conditions explained 37% of the performance variance. Pain intensity alone explained 27% and 18% of the self-reported and performance based disability, respectively.ConclusionFindings indicate that primary health care interventions should target pain intensity, depressive symptoms and physical activity as a means to preventing or decreasing both self-reported and performance based disability.     

Optimal freezing and thawing for the survival of periphheral nerves in severed rabbit limbs

This study aimed to investigate the optimal freezing and thawing procedures for the survival of peripheral nerves in severed rabbit limbs. Twenty New Zealand White rabbits were randomized into four groups: normal control, slow-freezing fast-thawing, slow-freezing slow-thawing, fast-freezing fast-thawing, with five animals in each group. The hind limbs of the rabbits were severed at 1 cm above the knee joint. The severed limbs were cryopreserved with various freezing and thawing procedures. The sciatic nerves were harvested and trypsinized into single nerve fibers for morphological evaluation. The cell viability of the nerve fibers was examined by staining with Calcein-AM and propidium iodide. The fluorescent intensity of the nerve fibers was measured with a laser scanning confocal microscope. The morphology of the nerve fibers in the slow-freezing fast-thawing group was very similar with that of the normal control group, with only mild demyelination. The slow-freezing fast-thawing group and slow-freezing slow-thawing group showed severely damaged nerve fibers. The fluorescent intensities of the nerve fibers was significantly different among the four groups, with a decreasing order of normal control, slow-freezing fast-thawing, slow-freezing slow-thawing, and fast-freezing fast-thawing (P < 0.05). Of the various cryopreservative procedures, slow-freezing fast thawing has the minimal effects on the survival of nerve fibers in severed rabbit limbs.     

Hospital mortality and optimality of nursing workload: A study on the predictive validity of the RAFAELA Nursing Intensity and Staffing system

BackgroundPatient classification systems have been developed to manage workloads by estimating the need for nursing resources through the identification and quantification of individual patients’ care needs. There is in use a diverse variety of patient classification systems. Most of them lack validity and reliability testing and evidence of the relationship to nursing outcomes.ObjectivePredictive validity of the RAFAELA system was tested by examining whether hospital mortality can be predicted by the optimality of nursing workload.MethodsIn this cross-sectional retrospective observational study, monthly mortality statistics and reports of daily registrations from the RAFAELA system were gathered from 34 inpatient units of two acute care hospitals in 2012 and 2013 (n = 732). The association of hospital mortality with the chosen predictors (hospital, average daily patient to nurse ratio, average daily nursing workload and average daily workload optimality) was examined by negative binomial regression analyses.ResultsCompared to the incidence rate of death in the months of overstaffing when average daily nursing workload was below the optimal level, the incidence rate was nearly fivefold when average daily nursing workload was at the optimal level (IRR 4.79, 95% CI 1.57–14.67, p = 0.006) and 13-fold in the months of understaffing when average daily nursing workload was above the optimal level (IRR 12.97, 95% CI 2.86–58.88, p = 0.001).ConclusionsHospital mortality can be predicted by the RAFAELA system. This study rendered additional confirmation for the predictive validity of this patient classification system. In future, larger studies with a wider variety of nurse sensitive outcomes and multiple risk adjustments are needed. Future research should also focus on other important criteria for an adequate nursing workforce management tool such as simplicity, efficiency and acceptability.     

Evaluating the safety profile of focused ultrasound and microbubble-mediated treatments to increase blood-brain barrier permeability

Introduction: Treatment of several diseases of the brain are complicated by the presence of the skull and the blood-brain barrier (BBB). Focused ultrasound (FUS) and microbubble (MB)-mediated BBB treatment is a minimally invasive method to transiently increase the permeability of blood vessels in targeted brain areas. It can be used as a general delivery system to increase the concentration of therapeutic agents in the brain parenchyma.

Areas covered: Over the past two decades, the safety of using FUS+MBs to deliver agents across the BBB has been interrogated through various methods of imaging, histology, biochemical assays, and behavior analyses. Here we provide an overview of the factors that affect the safety profile of these treatments, describe methods by which FUS+MB treatments are controlled, and discuss data that have informed the assessment of treatment risks.

Expert opinion: There remains a need to assess the risks associated with clinically relevant treatment strategies, specifically repeated FUS+MB treatments, with and without therapeutic agent delivery. Additionally, efforts to develop metrics by which FUS+MB treatments can be easily compared across studies would facilitate a more rapid consensus on the risks associated with this intervention.