Analysis of ASPM in an ethnically diverse cohort of 400 patient samples: perspectives of the molecular diagnostic laboratory

Primary Autosomal Recessive Microcephaly (MCPH) is characterized by congenital microcephaly usually without additional clinical findings. The most common gene implicated in MCPH is ASPM and a large percentage of mutations described have been homozygous and in consanguineous families primarily of East Asian and Middle Eastern origin. ASPM sequencing was performed on 400 patients between the years 2009 and 2012. Seventy of the patient samples were also analyzed for copy number changes in the ASPM gene. Forty protein truncating mutations, including 29 novel mutations, were identified in 39 patients with MCPH. Approximately one third of patients were compound heterozygotes, indicative of non‐consanguinity in these patients. In addition, 46 non‐synonymous variants were identified and interpreted as variants of uncertain significance. No deletion/duplication in ASPM was identified in the patients analyzed. A wide ethnic distribution was observed, including the first reported patients with ASPM‐related MCPH of Hispanic descent. Clinical information was collected for 26 of the ASPM‐positive patients and 41 of the ASPM‐negative patients. As more individuals are identified with MCPH, we anticipate that we will continue to identify ASPM mutation‐positive patients from all ethnic origins supporting the occurrence of this genetic condition beyond that of consanguineous families of certain ethnic populations.     

Active tuberculosis in inflammatory bowel disease patients under treatment from an endemic area in Latin America

BACKGROUNDThere has been an increase in cases of inflammatory bowel disease (IBD) in recent years. There is also greater access and availability of immunosuppressive and biological agents, which increase the risk of opportunistic infection despite improving the quality of life and promoting mucosal healing. Tuberculosis (TB) remains a public health problem, and it has a high incidence in several countries. Therefore, knowledge of the risk of developing TB in patients with IBD is important.AIMTo evaluate the risk of active TB in patients with IBD under treatment from an endemic area in Latin America.METHODSA standard questionnaire included demographic variables, clinical aspects of IBD disease, history of active TB during treatment, active TB characteristics and evolution, initial screening and results and time from the start of anti-tumor necrosis factor alpha (TNFα) to TB development.RESULTSAzathioprine, anti-TNFα and the combination of these two drugs were associated with a higher risk of active TB incidence. The TNFα blockers increased the relative risk of developing active TB compared to other treatments. All four multivariable models showed that the use of TNFα blockers alone or in combination with azathioprine was an important risk factor for the incidence of active TB. After adjustment for sex, age, type of IBD and latent TB, anti-TNFα with azathioprine increased the relative risk to 17.8 times more than conventional treatment. Late TB, which was diagnosed 3 mo after the start of anti-TNFα, was the most frequent.CONCLUSIONTreatment with anti-TNFα increased the risk of active TB in IBD patients from an endemic area in Latin America. This risk was increased when anti-TNFα was combined with azathioprine. The time from the beginning of the treatment to the active TB diagnosis suggests a new TB infection.     

金属对金属大头径微创全髋关节置换术治疗青中年股骨头坏死的临床研究

目的探讨金属对金属（金对金）大头径假体微创全髋关节置换术（THA）治疗青中年股骨头坏死Ⅲ、Ⅳ期的临床疗效。方法本组32例（35髋）青中年股骨头缺血性坏死Ⅲ、Ⅳ期患者,年龄24～59岁,平均45岁,术前髋关节Harris评分平均（37．9±7．5）分;以改良后外侧小切口、肌间隙人路、充分保留关节动力性组织结构为特征的金对金大头径微创THA治疗。术中严格采取正确的假体植入技术,术中保留完整的软骨下骨和髋臼横韧带,击入臼杯时一次性安装成功,正确运用万古霉素预防感染。术后口服利伐沙班片抗凝,术后12h开放负压引流及卧床行功能锻炼,术后第2天拔除引流管后扶拐下地部分负重行走,术后2—3周患者即可弃拐完全负重行走。结果本组32例35髋患者均获随访,随访时间为12个月～6年,平均为4年。所有患者切口均一期愈合,无深静脉血栓形成、关节脱位、坐骨神经损伤、髋臼及股骨疲劳骨折、关节疼痛等严重并发症,X线片示髋关节假体位置均良好,无松动、移位、股骨柄下沉、假体周围骨折等表现。末次随访Harris评分由术前平均（37．9±7．5）分,提高至术后平均（92．2±4．6）分,前后比较有统计学意义（t=44．341,P〈0．05）。所有患者末次随访时髋关节功能明显优于术前,均对治疗效果满意,完全恢复正常生活及工作。结论采用金对金大头径微创THA治疗青中年股骨头坏死Ⅲ、Ⅳ期患者,能够明显降低手术风险,缩短卧床时问,迅速恢复髋关节功能,减少手术并发症,取得了满意的近期临床疗效。随着基础和临床研究的不断深入,金对金大头径髋关节假体的长期疗效还需要进一步探讨。     

腹腔镜巨大前列腺囊腺瘤切除一例报告并文献复习

目的提高对巨大前列腺囊腺瘤的认识。方法回顾性分析收治的1例巨大前列腺囊腺瘤并成功进行腹腔镜切除的临床资料,结合文献复习进行讨论。结果本例患者成功行腹腔镜完整切除,手术时间125min,出血量60ml,术中双侧精囊输精管完整保留,术后会阴部坠胀不适消失,复查精液常规精子数目及活动度正常。已随诊12个月,肿瘤无复发。结论巨大前列腺囊腺瘤罕见,最终确诊要依靠病理诊断,其最有效的治疗是手术完整切除,而腹腔镜途径可作为完整切除的微创手段。     

Impact of medical and surgical intervention on survival in patients with cholangiocarcinoma

AIM:To examine surgical and medical outcomes for patients with cholangiocarcinoma using a populationbased cancer registry.METHODS:Using the California Cancer Registry’s Cancer Surveillance Program,patients with intrahepatic cholangiocarcinoma treated in Los Angeles County from 1988 to 2006 were identified and evaluated for clinical and pathologic factors and therapies received(surgery,radiation,and chemotherapy).The surgical cohort was further categorized into three treatment groups:patients who received adjuvant chemotherapy,adjuvant chemoradiation,or underwent surgery alone(no chemotherapy or radiation administered).Survival was assessed by Kaplan-Meier method;and Cox proportional hazard modeling was used in multivariate analysis.RESULTS:Of 825 patients,60.2% received no treatment.Of the remaining 328 patients,18.5% chemotherapy only,7.4% chemoradiation,and 13.8% underwent surgery.More male patients underwent surgical resection(P = 0.004).Surgical patients were younger than the patients receiving chemotherapy or chemoradiation(P < 0.001).Of the surgical cohort(n = 114),60.5% underwent surgery alone while 39.5% underwent surgery plus adjuvant therapy(chemotherapy n = 20;chemoradiation,n = 21)(P < 0.001).Median survival for all patients in the study was 6.6 mo.Median survival was highest for patients who underwent surgery(23 mo),whereas both chemotherapy(9 mo) and chemoradiation(8 mo) alone were each less effective(P < 0.001).By multivariate analysis,extent of disease,receipt of surgery,and administration of chemotherapy(with/without surgery) were independent predictors of overall survival.CONCLUSION:This study demonstrates that surgery is a critical treatment modality.Multimodality treatment has yet to be standardized,but play a role in optimal therapy for cholangiocarcinoma.     

八项肝纤维化血清标志物比较研究

目的比较血清血小板衍生生长因子-BB(PDGF-BB)、转化生长因子-β1(TGF-B1)、基质金属蛋白酶抑制剂-1(TIMP-1)、基质金属蛋白酶-1(MMP-1)、透明质酸(HA)、Ⅲ型前胶原(PC Ⅲ)、Ⅳ型胶原(C Ⅳ)和层黏连蛋白(LN)及外周血单个核细胞(PBMC)内TIMP-1 mRNA、MMP-1 mRNA在肝纤维化中的诊断价值。方法常规肝穿活检、组织病理学诊断；RT-PCR检测PBMCs中MMP-1 mRNA、TIMP-1 mRNA水平；酶标法检测血清PDGF-BB、TGF-β1、TIMP-1和MMP-1含量；放射免疫法检测血清HA、PC Ⅲ、C-Ⅳ和LN含量。结果经ROC曲线分析，血清PDGF-BB、TIMP-1、HA、PC Ⅲ、C-Ⅳ、LN和TIMP-1 mRNA的AUC分别为0．985、0．726、0．318、0．728、0．727、0．583、0．463、0．876；血清PDGF-BB和PBMCs中TIMP-1 mRNA的灵敏度和特异度分别为90％、95％，73．7％、100％；两者联合检测的灵敏度为97．4％，特异度为95．0％。结论八项指标中，血清PDGF-BB的诊断价值最大。在筛选肝纤维化患者时，以血清PDGF-BB、PBMC中TIMP-1 mRNA联合检测最佳。     

Prognostic significance of thrombocytosis in idiopathic sideroblastic anemia

In order to determine the prognostic significance of thrombocytosis in idiopathic sideroblastic anemia, the clinical courses of 17 patients were reviewed. Six patients (36%) had thrombocytosis, and none developed acute leukemia. Nine patients (53%) had normal platelet counts, and one developed acute leukemia. Two patients (12%) were thrombocytopenic, and one died of acute leukemia. There was little correlation between survival and platelet count. Sixty-three additional case reports of idiopathic sideroblastic anemia were collected from the literature. Analysis of those patients and the patients in the present study documented transformation to acute leukemia in 5 of 9 (56%) thrombocytopenic patients, 4 of 54 (7.4%) patients with normal platelet counts, and 0 of 17 patients with thrombocytosis (p less than 0.05). Therefore patients with idiopathic sideroblastic anemia and thrombocytosis appear to have a decreased likelihood of leukemic transformation.