Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation

We report here on a preliminary human autologous transplantation study of retroviral gene transfer to bone marrow (BM) and peripheral blood (PB)-derived CD34-enriched cells. Eleven patients with multiple myeloma or breast cancer had cyclophosphamide and filgrastim-mobilized PB cells CD34-enriched and transduced with a retroviral marking vector containing the neomycin resistance gene, and CD34-enriched BM cells transduced with a second marking vector also containing a neomycin resistance gene. After high-dose conditioning therapy, both transduced cell populations were reinfused and patients were followed over time for the presence of the marker gene and any adverse effects related to the gene-transfer procedure. All 10 evaluable patients had the marker gene detected at the time of engraftment, and 3 of 9 patients had persistence of the marker gene for greater than 18 months posttransplantation. The marker gene was detected in multiple lineages, including granulocytes, T cells, and B cells. The source of the marking was both the transduced PB graft and the BM graft, with a suggestion of better long-term marking originating from the PB graft. The steady- state levels of marking were low, with only 1:1000 to 1:10,000 cells positive. There was no toxicity noted, and patients did not develop detectable replication-competent helper virus at any time posttransplantation. These results suggest that mobilized PB cells may be preferable to BM for gene therapy applications and that progeny of mobilized peripheral blood cells can contribute long-term to engraftment of multiple lineages.     

Changes in Swallowing Physiology and Patient Perception of Swallowing Function Following Chemoradiation for Head and Neck Cancer

Patients treated with chemoradiation for head and neck cancer often report difficulty with swallowing and are frequently diagnosed with dysphagia. The extent to which patient awareness of dysphagia corresponds to observed physiologic changes in swallowing is unclear. The purpose of this study was to determine how both patient awareness of swallowing function and swallowing physiology individually change following chemoradiation and then to clarify the relationship between them. Twenty-one patients with head and neck cancer treated with chemoradiation were assessed before and after treatment and matched with twenty-one control subjects. The modified barium swallow test was utilized to examine swallowing physiology. Each subject was also given a series of items regarding awareness of specific dysphagia symptoms. Results showed decreased swallow efficiencies, higher percentages of residue, and more occurrences of penetration and aspiration following chemoradiation. Patients also had significantly higher ratings for 4 of the 12 items (“dry mouth,” “food sticking in my mouth,” “need water to help food go down,” and “change in sense of taste”). Only one strong and significant correlation was found between ratings for “I have difficulty swallowing” and swallow efficiency values. Based on these findings, it appears that patients sense a general difficulty with swallowing but have less awareness of specific symptoms of dysphagia.     

河北省儿童医院住院患儿EB病毒感染流行病学特征

目的了解河北省儿童医院住院患儿EB病毒(EBV)感染的流行病学特征,为儿童EBV感染的诊断和预防提供科学依据。方法收集2017年1—12月河北省儿童医院0~14岁EBV感染住院患儿的全血样本,采用酶联免疫吸附试验(ELISA)检测其EBV衣壳抗原(VCA)IgG及IgM抗体,抗早期抗原(EA)IgG抗体和抗核抗原1(NA1)IgG抗体,以检测结果为研究样本的抗体谱。根据4种EBV抗体的检测结果分为现症感染(抗VCA-IgM抗体阳性,抗NA1-IgG抗体阴性、抗VCA-IgG抗体、抗EA-IgG抗体阳性或阴性)、亚急性感染(抗VCA-IgG抗体阳性,抗VCA-IgM抗体、抗NA1-IgG抗体、抗EA-IgG抗体阳性或阴性)、既往感染(抗NA1-IgG抗体阳性,抗VCA-IgG抗体阳性或阴性,其他抗体均为阴性)和未感染(4种抗体均阴性)。按照患儿年龄、检出月份和性别分析各组的阳性率。结果共纳入符合要求的样本4 451例,其中3 257例(73.17%)抗体谱提示EBV感染,包括现症感染380例(8.54%)、亚急性感染616例(13.84%)、既往感染2 261例(50.80%)。不同年龄组原发阳性检出率差异有统计学意义(P<0.05),其中学龄前(>3岁)组的阳性检出率最高(P<0.05);不同检出月份组阳性检出率差异有统计学意义(P<0.05),7月份阳性检出率高于其他月份(P<0.05);男性患儿与女性患儿EBV感染率差异无统计学意义(P>0.05)。380例现症感染患儿的疾病谱以血液系统疾病[传染性单核细胞增多症、急性粒细胞缺乏症、血小板减少性紫癜、EBV相关嗜血细胞综合征]为主,其中传染性单核细胞增多症为临床常见疾病;其次是呼吸系统疾病(急性支气管炎、疱疹性咽峡炎、急性扁桃体炎);其他疾病谱包括神经系统疾病及血流感染、肾病综合征、川崎病。结论河北省儿童医院住院患儿EBV阳性检出率有年龄和检出月份差异,现症感染以血液系统疾病患儿为主,医院应根据流学病学特征制定相应预防措施。     

流式细胞术的培训实践及技术平台建设探讨

流式细胞分析技术(flow cytometry,FCM),又称流式细胞术,是一种在功能水平上对单细胞或其他生物粒子进行定量分析和分选的技术,具有广泛的科研应用价值.采用理论与实践并举,结合讨论的教学方式,在教师队伍开设针对性的培训课程,对深刻理解并在科研工作中有效利用该技术具有及其重要意义.同时以教学促科研,以科研促技...     

Strategies for improving outcomes of COPD exacerbations

COPD is uniquely situated as a chronic disease at the beginning of the 21st century; it is not only an established major cause of mortality and morbidity but is increasing in prevalence despite current medical interventions. In addition COPD is not a stable disease but its natural history is punctuated by periods of acute deterioration or exacerbations. Exacerbations generate considerable additional morbidity and mortality, and directly affect patients’ quality of life. However, despite significant advances in understanding and treating this disease, exacerbations continue to be the major cause of COPD-associated hospitalization, and provision for their management incurs considerable health care costs. This review will consider the current management of COPD exacerbations and how new clinical strategies may improve outcome of these important clinical events.     

Integration of Merged Delayed‐Enhanced Magnetic Resonance Imaging and Multidetector Computed Tomography for the Guidance of Ventricular Tachycardia Ablation: A Pilot Study

MDCT/MRI Fusion for the Guidance of VT Ablation . Background: Delayed enhancement (DE) MRI can assess the fibrotic substrate of scar‐related VT. MDCT has the advantage of inframillimetric spatial resolution and better 3D reconstructions. We sought to evaluate the feasibility and usefulness of integrating merged MDCT/MRI data in 3D‐mapping systems for structure–function assessment and multimodal guidance of VT mapping and ablation. Methods: Nine patients, including 3 ischemic cardiomyopathy (ICM), 3 nonischemic cardiomyopathy (NICM), 2 myocarditis, and 1 redo procedure for idiopathic VT, underwent MRI and MDCT before VT ablation. Merged MRI/MDCT data were integrated in 3D‐mapping systems and registered to high‐density endocardial and epicardial maps. Low‐voltage areas (<1.5 mV) and local abnormal ventricular activities (LAVA) during sinus rhythm were correlated to DE at MRI, and wall‐thinning (WT) at MDCT. Results: Endocardium and epicardium were mapped with 391 ± 388 and 1098 ± 734 points per map, respectively. Registration of MDCT allowed visualization of coronary arteries during epicardial mapping/ablation. In the idiopathic patient, integration of MRI data identified previously ablated regions. In ICM patients, both DE at MRI and WT at MDCT matched areas of low voltage (overlap 94 ± 6% and 79 ± 5%, respectively). In NICM patients, wall‐thinning areas matched areas of low voltage (overlap 63 ± 21%). In patients with myocarditis, subepicardial DE matched areas of epicardial low voltage (overlap 92 ± 12%). A total number of 266 LAVA sites were found in 7/9 patients. All LAVA sites were associated to structural substrate at imaging (90% inside, 100% within 18 mm). Conclusion: The integration of merged MDCT and DEMRI data is feasible and allows combining substrate assessment with high‐spatial resolution to better define structure–function relationship in scar‐related VT. (J Cardiovasc Electrophysiol, Vol. 24, pp. 419‐426, April 2013)     

Effect of a maxillary glossectomy prosthesis on articulation and swallowing

Swallowing was found to be substantially improved with the prosthesis. Less aspiration, less time necessary to complete the swallow, and greater variation in food consistency tolerated were all positive results of the prosthesis. In addition, videofluoroscopic studies of tongue movements during speech revealed that tip-alveolar /t-d/ and back-velar /k-g/ productions were more normal with the prosthesis. With the prosthesis, the understandibility of /t/ and /d/ was improved 20% and that of /k/ and /g/, 33%. It is clear that compromises must be effected in prosthesis design to facilitate improvement in both speech and swallowing. A large prosthetic mass in the oral cavity can also negatively change speech resonance. These issues are being investigated, as are acoustic and perceptual studies of speech articulation. Future research should address whether a combination of maxillary and mandibular prostheses would result in better speech and swallowing function. A mandibular prosthesis could replace missing teeth and alveolar contour that might influence speech and swallowing. A mandibular prosthesis might also allow construction of a smaller maxillary glossectomy prosthesis to interact with the mandibular prosthesis.     

Three-dimensional printing in paediatric orthopaedic surgery

Three-dimensional (3D) printing is a rapidly evolving and promising field to improve outcomes of orthopaedic surgery. The use of patient-specific 3D-printed models is specifically interesting in paediatric orthopaedic surgery, as limb deformity corrections often require an individual 3D treatment. In this editorial, various operative applications of 3D printing in paediatric orthopaedic surgery are discussed. The technical aspects and the imaging acquisition with computed tomography and magnetic resonance imaging are outlined. Next, there is a focus on the intraoperative applications of 3D printing during paediatric orthopaedic surgical procedures. An overview of various upper and lower limb deformities in paediatrics is given, in which 3D printing is already implemented, including post-traumatic forearm corrections and proximal femoral osteotomies. The use of patient-specific instrumentation (PSI) or guiding templates during the surgical procedure shows to be promising in reducing operation time, intraoperative haemorrhage and radiation exposure. Moreover, 3D-printed models for the use of PSI or patient-specific navigation templates are promising in improving the accuracy of complex limb deformity surgery in children. Lastly, the future of 3D printing in paediatric orthopaedics extends beyond the intraoperative applications; various other medical applications include 3D casting and prosthetic limb replacement. In conclusion, 3D printing opportunities are numerous, and the fast developments are exciting, but more evidence is required to prove its superiority over conventional paediatric orthopaedic surgery.     

Impact of the microenvironment on the pathogenesis of mucosa-associated lymphoid tissue lymphomas

Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphomas of mucosa-associated lymphoid tissue (MALT), also known as MALT lymphomas. These arise at a wide range of different extranodal sites, with most cases affecting the stomach, the lung, the ocular adnexa and the thyroid. The small intestine is involved in a lower percentage of cases. Lymphoma growth in the early stages is associated with long-lasting chronic inflammation provoked by bacterial infections (e.g., Helicobacter pylori or Chlamydia psittaci infections) or autoimmune conditions (e.g., Sjögren’s syndrome or Hashimoto thyroiditis). While these inflammatory processes trigger lymphoma cell proliferation and/or survival, they also shape the microenvironment. Thus, activated immune cells are actively recruited to the lymphoma, resulting in either direct lymphoma cell stimulation via surface receptor interactions and/or indirect lymphoma cell stimulation via secretion of soluble factors like cytokines. In addition, chronic inflammatory conditions cause the acquisition of genetic alterations resulting in autonomous lymphoma cell growth. Recently, novel agents targeting the microenvironment have been developed and clinically tested in MALT lymphomas as well as other lymphoid malignancies. In this review, we aim to describe the composition of the microenvironment of MALT lymphoma, the interaction of activated immune cells with lymphoma cells and novel therapeutic approaches in MALT lymphomas using immunomodulatory and/or microenvironment-targeting agents.