In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction

Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.     

Near-infrared fluorescence imaging improves the nodal yield in neck dissection in oral cavity cancer – A randomized study

IntroductionLymph node yield (LNY) in neck dissection has been identified as a prognostic factor in oral cavity cancer. The purpose of this study was to investigate the impact of additional use of optical imaging on LNY in therapeutic ND in oral cancer.MethodsConsecutive patients with oral squamous cell carcinoma with clinical neck metastasis planned for primary tumor resection were randomized to conventional neck dissection or near-infrared fluorescence (NIRF)-guided neck dissection, respectively. In the intervention group, patients were injected with ICG-Nanocoll prior to surgery. Intraoperatively, an optical hand-held camera system was used for lymph node identification. Also, NIRF imaging of the neck specimen was performed, and optical signals were pinned with needle markings to guide the pathological examination. The endpoint of the study was LNY per neck side in levels Ib-III.Results31 patients were included with 18 neck sides in the control group and 18 neck sides in the intervention group for evaluation. During NIRF-guided ND, individual lymph nodes could be identified by a bright fluorescent signal and individual tumor-related drainage patterns could be observed in the neck. The LNY in the intervention group was significantly higher compared to the control group (p = 0.032) with a mean of 24 LN (range: 12–33 LN in levels Ib-III compared to 18 LN (range: 10–36 LN) in the control group, respectively.ConclusionsNIRF-guided ND significantly improved the nodal yield compared to the control group. Intraoperative real-time optical imaging enabled direct visualization of tumor-related drainage patterns within the neck lymphatics.     

肝癌介入术治疗患者术中应用心理护理的效果

目的研究在肝癌介入术治疗患者中应用心理护理干预的临床价值。方法本文数据计算目标是2018年1月-2019年6月的60例肝癌介入术治疗患者,以随机数字表法的形式进行分组研究,常规组(n=30)开展一般护理干预,心理组(n=30)开展心理护理干预,比较心理组与常规组肝癌介入术治疗患者临床护理情况。结果心理组肝癌介入术治疗患者治疗后临床护理满意度、焦虑评分、抑郁评分与常规组比较,两组治疗后肝癌介入术治疗患者焦虑评分、抑郁评分与治疗前比较,P<0.05,差异有统计学意义。结论将心理护理干预应用在肝癌介入术治疗患者中可提升护理满意度。     

Clinical implications,diagnosis,and management of diabetes in patients with chronic liver diseases

Diabetes mellitus(DM) negatively affects the development and progression of chronic liver diseases(CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma(HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.     

肝内胆管癌新辅助治疗共识与争议

肝内胆管癌（ICC）恶性程度高，症状隐匿，早期症状不明显，由于缺乏有效的筛查，确诊时多处于进展期，大多失去手术切除机会。目前，根治性手术仍是惟一可以使病人获得长期生存的治疗方式，但存在切除率低、术后易复发等难题。新辅助治疗能缩小原有病灶及转移的淋巴结，提高R0切除率，对于无法切除的局部晚期ICC，新辅助治疗可使局部进展的ICC降期为可切除，也可改善肝移植病人的预后。但目前对ICC行新辅助治疗的潜在效用仍存在争议。     

A novel technique to measure severity of pediatric pectus excavatum using white light scanning.

Background/purpose

Computed tomography (CT) derived Haller Index (HI) remains the standard for quantifying severity in patient with pectus excavatum (PE). Optical scanning described in literature reports optimistic results and new indices that correlate with HI. This study assessed the feasibility of a handheld White Light Scanner (WLS) to obtain 3D measurements and indices of PE deformity.

Quantification of 5-HT1A and 5-HT2A receptor Binding in Depressed Suicide Attempters and Non-Attempters

Objective: To determine serotonin system abnormalities related to major depression or previous suicidal behavior.

Methods: [¹¹C]WAY100635, [¹⁸F]altanserin and positron emission tomography were used to compare 5-HT_1A and 5-HT_2A binding in MDD patients divided into eight past suicide attempters (>4yrs prior to scanning) and eight lifetime non-attempters, and both groups were compared to eight healthy volunteers.

Results: The two receptor types differed in binding pattern across brain regions from each other, but there were no differences in binding between healthy volunteers and the two depressed groups or between depressed suicide attempters and non-attempters. No effects of depression severity or lifetime aggression were observed for either receptor.

Conclusion: Limitations of this study include small sample size and absence of high lethality suicide attempts in the depressed attempter group. No trait-like binding correlations with past suicide attempt or current depression were observed. Given the heterogeneity of nonfatal suicidal behavior, a larger sample study emphasizing higher lethality suicide attempts may find the serotonin biological phenotype seen in suicide decedents.