集束化干预联合闭环管理对ICU多重耐药菌感染的防控效果

目的 探讨集束化干预策略联合闭环管理模式对ICU多重耐药菌感染的防控效果。方法选取2020年1~12月EICU住院患者275例作为对照组，实施常规管理；2021年1~10月EICU住院患者239例作为观察组，在常规管理基础上实施集束化干预策略联合闭环管理。结果实施后，观察组多重耐药菌感染发生率明显低于对照组；患者住院日显著低于对照组，4项护理措施执行率(隔离标识、手卫生、环境消毒、医务人员相关知识知晓)、病原学送检率显著高于对照组（均P<0.05）。结论集束化干预联合信息化闭环管理可有效降低EICU多重耐药菌感染发生率。     

双侧延髓内侧梗死临床分析

目的分析并探究双侧延髓内侧梗死(BMMI)的血管病因、临床表现、MRI特征和预后,以期提高BMMI的早期诊断率.方法对青岛大学附属烟台毓璜顶医院诊治的14例BMMI患者临床资料进行分析.结果BMMI血管病因以动脉粥样硬化为主;临床症状表现为四肢瘫痪、舌瘫、感觉异常、头晕、构音障碍、饮水呛咳等,危重时出现呼吸衰竭.头颅DWI示双侧延髓内侧可呈特征性"心型"、"Y"字型、"V"字型或倒"八"字型高信号影.出院NIHSS评分、卒中进展(尤其呼吸衰竭)为BMMI的预后不良因素.结论BMMI临床少见,临床表现多样,预后较差;头颅MRI为其主要的影像学检查,有助于早期诊断.     

Thinned-out skin paddle versus collagen matrix as an optimized peri-implant soft tissue following fibula osteoseptocutaneous free flap: 3-year retrospective study

The objective of this study was to compare the implant longevity following two methods of peri-implant soft tissue optimization following free fibula flap (FFF): thinning of skin paddle (SP) and collagen matrix (CM). All patients who underwent rehabilitation with dental implants after mandibular reconstruction with FFF between June 2009 to May 2014 were retrospectively reviewed. Two methods of peri-implant soft tissue optimization were applied: (1) SP group, (2) CM group. Outcome measurements were: modified plaque index (mPI), modified sulcus bleeding index (mSBI), probing depth (PD), marginal bone loss (MBL), implant success rate and complication rates. A total of 24 patients with 69 implants were included in the study, with 8.7% (n = 6) of implants lost in 3 years. No statistically significant difference was found regarding the outcome measurements in both groups. Failed implants presented with statistically significant higher mPI, mSBI, PD and MBL scores during prosthesis delivery and subsequent follow-ups (P<0.03). In the SP group, one patient experienced SP necrosis which later underwent soft tissue optimization using CM. CM is an alternative peri-implant soft tissue, while thinning of SP is feasible if thickness is well controlled.     

高危原发前列腺胃肠道外间质瘤诊疗体会及文献复习

目的探讨前列腺原发胃肠道外间质瘤诊治要点。 方法回顾性分析我院2017年9月诊治的1例高危原发性前列腺胃肠道外间质瘤临床病理特征资料、随访情况，总结现有文献讨论总结本病诊治心得。 结果65岁男性，因"前列腺电切术后2年，反复血尿3个月余"入院。术前MRI考虑为来源不清的盆腔巨大实性占位（115 mm×105 mm×85 mm），经直肠穿刺诊断为梭形细胞来源的肿瘤。行盆腔肿瘤切除+膀胱前列腺腺切除+盆腔淋巴结清扫术+Bricker术。术后病理提示为前列腺原发胃肠道外间质瘤[CD117（+）；Dog1（+）；CD34（+）；PSA（+）；AR（+）；P504s（+）；Ki-67（2%）]。术后肿瘤组织全外显子测序提示为C-Kit基因（Exon 11 p.Q556-V560del）存在明显临床意义突变，筛选靶向药物甲磺酸伊马替尼+比卡鲁胺（PSA平稳后停用）口服，术后随访18个月无肿瘤复发及不良并发症。 结论前列腺原发胃肠道外间质瘤罕见，需与前列腺其他良恶性肿瘤相鉴别诊断。全外显子测序了解其发病高危基因，同时筛选药物辅助治疗可使患者生存获益。     

Apical U-shape splitting technique for undercut areas of the anterior alveolar ridge: a prospective non-randomized controlled study

The aim of this study was to investigate a novel apical U-shape splitting technique for horizontal bone augmentation in undercut areas and to compare its efficacy with that of guided bone regeneration (GBR). This was a prospective non-randomized controlled clinical trial. A total of 36 patients, who presented with a labial undercut that was not able to house a normally inclined implant, underwent the new technique or GBR. Radiographic and clinical data were obtained preoperatively, immediately after surgery, and 12 months after surgery. Pairwise comparisons of changes in ridge width gain, marginal bone loss, and pink aesthetic score were performed; correlations with pristine ridge morphology were investigated. The results showed similar marginal bone loss in the two groups. The overall ridge width gains in the new technique group (2.56 ± 1.92 mm) and GBR group (0.73 ± 1.21 mm) differed significantly (P < 0.05). The pink aesthetic score was higher for the new technique group (11.75 ± 1.22) than for the GBR group (9.25 ± 1.86) (P < 0.01). The morphology of the concavity had different impacts on regeneration in the two groups. The apical U-shape splitting technique, as a safe and effective alternative to GBR, provided a significant increase in bone volume gain where labial fenestration was inevitable during implant placement.     

In vitro dissolution and oral bioavailability study of fenofibrate nanomatrix system prepared by hot-melt extrusion

Solvent evaporation method for preparation of nanomatrix has the disadvantages, such as residual organic solvent, environmental pollution, explosion-proofing and so on. To overcome these shortcomings, a series of fenofibrate nanomatrix drug delivery system (NDDS) consisting of nano-porous silica Sylysia^®350 (S350) and pH sensitive material Eudragit^® L100-55 (EL100-55) were prepared using hot-melt extrusion (HME), and their in vitro dissolution and in vivo bioavailability were compared. Finally, the formulation with the highest in vivo bioavailability was selected as the optimized formulation for DSC and PXRD characterization. The results showed that the optimized NDDS showed a higher bioavailability than the reference formulation, although there was crystalline form drug remaining in NDDS. The relative bioavailability of the optimized formulation was 157.1% compared with the commercial product Lipanthyl^®. In addition, the relative bioavailability of the optimized formulation was 124.8% in comparison with the formulation prepared by solvent evaporation method, showing that the NDDS prepared by the HME method was effective in improving the bioavailability of fenofibrate. In conclusion, HME was a promising method to prepare NDDS.     

Comparison of survival between adolescent and young adult vs older patients with hepatocellular carcinoma

BACKGROUNDDue to the special clinical features and biologic characteristics of adolescent and young adult (AYA) cancers, AYA cancers are different from cancers in children and elderly individuals. However, there are few reports on AYA hepatocellular carcinoma (HCC).AIMTo investigate the overall survival (OS) of AYA (15-39 years) and elderly (40-74 years) patients with HCC.METHODSThe data of all the HCC cases were extracted from the Surveillance, Epidemiology, and End Results database from 2004 to 2015 and were then divided into two groups based on age: AYA group (15-39 years) and older group (40-74 years). Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups. Propensity score matching (PSM) was employed to analyze the OS difference between the two groups. The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTSCompared to elderly cancer patients, AYA patients with HCC had a worse Surveillance, Epidemiology, and End Results stage, including the distant stage (22.1% vs 15.4%, P < 0.001), and a more advanced American Joint Committee on Cancer (AJCC) stage, including AJCC III and IV (49.2% vs 38.3%, P < 0.001), and were more likely to receive surgery (64.5% vs 47.5%, P < 0.001). Before PSM, the AYA group had a longer survival in months (median: 20.00, interquartile range [IQR]: 5.00-62.50) than the older group (median: 15.00, IQR: 4.00-40.00) (P < 0.001). After PSM, the AYA group still had a longer survival in months (median: 21.00, IQR: 5.00-64.50) than the older group (median: 18.00, IQR: 6.00-53.00) (P < 0.001). The Cox proportional hazards regression model showed that advanced age (hazard ratio [HR] = 1.405, 95%CI: 1.218-1.621, P < 0.001) was a risk factor for OS of HCC patients. In the subgroup analysis, the Cox proportional hazards regression model showed that in AJCC I/II HCC patients, advanced age (HR = 1.749, 95%CI: 1.352-2.263, P < 0.001) was a risk factor for OS, while it was not a risk factor in AJCC III/IV HCC patients (HR = 1.186, 95%CI: 0.997-1.410, P = 0.054) before PSM. After PSM, advanced age (HR = 1.891, 95%CI: 1.356-2.637, P < 0.001) was still a risk factor for OS in AJCC I/II HCC patients, but was not a risk factor for OS in AJCC III/IV HCC patients (HR = 1.192, 95%CI: 0.934-1.521, P = 0.157) after PSM.CONCLUSIONAYA patients with HCC have different clinical characteristics from older adults. In different AJCC stages, the two groups of patients have different OS: In AJCC I/II HCC patients, advanced age is a risk factor for OS, but it is not a risk factor for OS in the AJCC III/IV HCC patient group.     

Understanding and adjusting for the selection bias from a proof-of-concept study to a more confirmatory study

It has long been noticed that the efficacy observed in small early phase studies is generally better than that observed in later larger studies. Historically, the inflation of the efficacy results from early proof-of-concept studies is either ignored, or adjusted empirically using a frequentist or Bayesian approach. In this article, we systematically explained the underlying reason for the inflation of efficacy results in small early phase studies from the perspectives of measurement error models and selection bias. A systematic method was built to adjust the early phase study results from both frequentist and Bayesian perspectives. A hierarchical model was proposed to estimate the distribution of the efficacy for a portfolio of compounds, which can serve as the prior distribution for the Bayesian approach. We showed through theory that the systematic adjustment provides an unbiased estimator for the true mean efficacy for a portfolio of compounds. The adjustment was applied to paired data for the efficacy in early small and later larger studies for a set of compounds in diabetes and immunology. After the adjustment, the bias in the early phase small studies seems to be diminished.     

双反牵引复位结合PFNA治疗股骨粗隆间骨折的初步临床应用

目的探讨双反牵引技术辅助闭合复位PFNA内固定治疗股骨粗隆间骨折的临床效果。 方法选取2015年5月至2017年5月在本院接受治疗的80例股骨粗隆间骨折患者为研究对象，其中失访者10例，根据复位方式的区别，将其分为双反牵引复位组与牵引床复位组。对比两组手术时间、术中出血量等各项指标间的差异。 结果70例患者术后获得随访，随访率87.5%，平均随访14个月。男性31例，女性39例，平均年龄（83.8±0.5）岁。双反牵引组患者手术时间、出血量及术中骨折复位时间、术中透视次数[（76±11）min，（80±90）ml，（12±3）min，（20±2）次]少于牵引床组[（85±13）min，（100±104）ml，（25±3）min，（25±3）次]，差异具有统计学意义（t=1.624，P=0.043；t=-1.773，P=0.037；t=1.362, P=0.041；t=-2.757，P=0.035），双反牵引复位组术后1、3个月患侧髋、膝功能评分明显优于牵引床复位组（P<0.05），术后6、12个月两组髋膝功能评分比较，差异无统计学意义（P>0.05）。 结论双反牵引复位股骨粗隆间骨折操作简便，复位质量高，对周围组织血运保护好、时间短、康复快，近期疗效优。     

Identification of driver genes and somatic mutations in cell-free DNA of patients with pulmonary lymphangioleiomyomatosis

Next-generation sequencing of cell-free circulating DNA (cfDNA) has emerged as promising technique for identifying minimally invasive genomic profiling of tumor cells recently. However, it remains relatively unknown in LAM disease. In our study, paired cfDNA and genomic DNA (gDNA) in blood samples were obtained from 23 LAM patients and seven healthy controls to explore mutations profiles of targeted 70 cancer-related genes. As results, log2-based allele frequencies of mutations in cfDNA were significantly different from those of gDNA. By comparing the mutual mutations identified both in cfDNA and gDNA, a significant correlation was also observed. After removing mutations in gDNA, distinct somatic mutation profiles of cfDNA were observed in LAM patients. Forty of 70 targeted genes had recurrent mutations, of which ATM, BRCA2 and APC showed the highest frequency. Based on the mutation, correlation network constructed of 40 mutated genes, 11 hub genes bearing intensive interactions were highlighted, including BRCA1, BRCA2, RAD50, RB1, NF1, APC, MLH3, ATM, PDGFRA, PALB2 and BLM. Expression of the hub genes showed significant clusters between LAM patients and controls and that RAD50 and BRCA2 had the strongest associations with subject phenotypes. Myogenesis and estrogen response were confirmed to be positively regulated in LAM patients. Collectively, our study provided a landscape of genomic alterations in LAM and discovered several potential driver genes, that is, BRCA2 and RAD50, which shed a substantial light on the clinical application of key molecular markers and potential therapy targets for precision diagnosis and treatment in the future.