Transsinusoidal Portal Vein Embolization with Ethylene Vinyl Alcohol Copolymer (Onyx): A Feasibility Study in Pigs

Purpose

Portal vein embolization is performed to increase the future liver remnant before liver surgery in patients with liver malignancies. This study assesses the feasibility of a transsinusoidal approach for portal vein embolization (PVE) with the ethylene vinyl alcohol copolymer, Onyx.

Methods

Indirect portography through contrast injection in the cranial mesenteric artery was performed in eight healthy pigs. Onyx was slowly injected through a microcatheter from a wedged position in the hepatic vein and advanced through the liver lobules into the portal system. The progression of Onyx was followed under fluoroscopy, and the extent of embolization was monitored by indirect portography. The pigs were euthanized immediately (n?=?2), at 7?days (n?=?4), or at 21?days postprocedure (n?=?2). All pigs underwent necropsy and the ex vivo livers were grossly and histopathologically analyzed.

Results

Transsinusoidal PVE was successfully performed in five of eight pigs (63%). In 14 of 21 injections (67%), a segmental portal vein could be filled completely. A mean of 1.6 liver lobes per pig was embolized (range 1–2 lobes). There were no periprocedural adverse events. Focal capsular scarring was visible on the surface of two resected livers, yet the capsules remained intact. Histopathological examination showed no signs of recanalization or abscess formation. Mild inflammatory reaction to Onyx was observed in the perivascular parenchyma.

Conclusions

The porcine portal vein can be embolized through injection of Onyx from a wedged position in the hepatic vein. Possible complications of transsinusoidal PVE and the effect on contralateral hypertrophy need further study.     

Spontaneous speech of patients with gliomas in eloquent areas before and early after surgery

Background

Glioma patients often complain about problems in daily conversation. A detailed spontaneous speech analysis could provide more insight in these communicative problems; no previous studies are reported.

Objective

To select sensitive parameters in spontaneous speech pre- and post-operatively in patients with gliomas in eloquent areas.

Methods

We included 27 patients and 21 healthy controls. In addition to a naming and category fluency test, spontaneous speech was collected 1 month pre-operatively and 3 months post-operatively, and analysed with the variables: Self-corrections, Repetitions, Lexical Diversity, Incomplete Sentences and Mean Length of Utterance (MLUw). A correlation analysis was performed between the linguistic variables and tumour characteristics (grade, localisation and volume), treatment related factors, and between the linguistic variables and the language tasks.

Results

Pre-operatively, patients produced more Incomplete Sentences than the controls (p?<?0.001). Post-operatively, patients’ utterance length (MLUw) (p?<?0.05) was also deviant. The quality of the spontaneous speech was influenced by tumour grade and localisation. There was no influence of tumour volume or treatment-related factors. Pre- and post-operatively, patients’ performance on the naming and the fluency task deviated from normal (p?<?0.001). The majority of the linguistic variables did not correlate with the language tasks, pointing to a measurement of distinct linguistic aspects.

Conclusion

Pre- and post-operatively there was a disorder in naming, category fluency and spontaneous speech, partly influenced by tumour characteristics. A spontaneous speech analysis appeared to be a valuable addition to standardised language tasks. Both measurements are important tools to obtain a complete linguistic profile.     

Ultra‐low depth sequencing of plasma cell DNA for the detection of copy number aberrations in multiple myeloma

Cytogenetic abnormalities are powerful prognostic factors in multiple myeloma (MM) and are routinely analyzed by FISH on bone marrow (BM) plasma cells (PC). Although considered the gold standard, FISH experiments can be laborious and expensive. Therefore, array‐CGH (aCGH) has been introduced as an alternative approach for detecting copy number aberrations (CNA), reducing the number of FISH experiments per case and yielding genome‐wide information. Currently, next generation sequencing (NGS) technologies offer new perspectives for the diagnostic workup of malignant disorders. In this study, we examined ultra‐low depth whole genome sequencing (LDS) as a valid alternative for aCGH for the detection of CNA in BM PC in MM. To this end, BM aspirates obtained in a diagnostic setting from 20 MM cases were analyzed. CD138+ cell‐sorted samples were subjected to FISH analysis. DNA was extracted for subsequent aCGH and LDS analysis. CNA were detected by aCGH and LDS in all but one case. Importantly, all CNA identified by parallel first generation aCGH analysis were also detected by LDS, along with six additional CNA in five cases. One of these additional aberrations was in a region of prognostic importance in MM and was confirmed using FISH. However, risk stratification in these particular cases was unaffected. Thus, a perfectly concordant prognostication between array‐CGH and LDS was observed. This validates LDS as a novel and cost‐efficient tool for the detection of CNA in MM.     

Cerebrovascular effects of glibenclamide investigated using high-resolution magnetic resonance imaging in healthy volunteers

Glibenclamide inhibits sulfonylurea receptor (SUR), which regulates several ion channels including SUR1-transient receptor potential melastatin 4 (SUR1-TRPM4) channel and ATP-sensitive potassium (K_ATP) channel. Stroke upregulates SURl-TRPM4 channel, which causes a rapid edema formation and brain swelling. Glibenclamide may antagonize the formation of cerebral edema during stroke. Preclinical studies showed that glibenclamide inhibits K_ATP channel-induced vasodilation without altering the basal vascular tone. The in vivo human cerebrovascular effects of glibenclamide have not previously been investigated.In a randomized, double-blind, placebo-controlled, three-way cross-over study, we used advanced 3 T MRI methods to investigate the effects of glibenclamide and K_ATP channel opener levcromakalim on mean global cerebral blood flow (CBF) and intra- and extracranial artery circumferences in 15 healthy volunteers. Glibenclamide administration did not alter the mean global CBF and the basal vascular tone. Following levcromakalim infusion, we observed a 14% increase of the mean global CBF and an 8% increase of middle cerebral artery (MCA) circumference, and glibenclamide did not attenuate levcromakalim-induced vascular changes. Collectively, the findings demonstrate the vital role of K_ATP channels in cerebrovascular hemodynamic and indicate that glibenclamide does not inhibit the protective effects of K_ATP channel activation during hypoxia and ischemia-induced brain injury.     

TNF-α值与2型糖尿病胰岛素抵抗的关系

目的　探讨肿瘤坏死因子 -α(TNF -α)与 2型糖尿病胰岛素的关系。方法　用homa -R法选取有胰岛素抵抗 (IR组 )和无胰岛素抵抗 (NIR组 )的 2型糖尿病患者各 2 0例。另以 2 0名年龄及体重指数相匹配的人群的作为对照组 ,分别检测其空腹血糖、胰岛素 ,计算Homa -R值 ,用ELISA法检测TNF -α。结果　IR组的TNF -α与NIR组及对照组相比较明显增高 ,有统计学意义(P <0 0 5 ) ,IR组的空腹胰岛素水平及胰岛素抵抗指标Homa -R也显著高于NIR组及对照组 (P值为 <0 0 1) ,而三组间年龄、BMI、血脂、脂蛋白、血压均无显著性差异 (P >0 0 5 )。结论　血浆TNF -α水平与胰岛素抵抗呈密切相关 ,在 2型DM中有重要病理意义 ,可作为评估有无胰岛素抵抗的一项重要参考指标     

Patient-focused rehabilitation team cohesiveness in veterans administration hospitals

OBJECTIVE: To quantify the relation of hospital culture, 3 levels of leadership (hospital-level administrators, discipline-specific supervisors, attending physician on the team), and physician involvement to patient-focused rehabilitation team cohesiveness. DESIGN: Survey research. SETTING: 48 Veterans Administration hospitals (VAHs). PARTICIPANTS: Six hundred fifty members of 50 rehabilitation teams. INTERVENTIONS: Not applicable.Main outcome measures Scales measuring hospital culture, administrative support, supervisor expectations, attending physician support, and physician involvement (independent variables), and patient-focused rehabilitation team cohesiveness (dependent variable). Associations between scales were examined by using a hierarchical linear regression model. RESULTS: Patient-focused team rehabilitation cohesiveness was significantly (P<.05) associated with administrative support, supervisor expectations, attending physician support, and physician involvement (Wald chi(2)=1192.66, P<.0001) (R(2)=.6431). There was no statistically significant independent association with hospital culture. CONCLUSIONS: Expectations of discipline-specific supervisors and hands-on team leadership and involvement by the attending physician were associated to a significant degree with the extent to which rehabilitation teams in VAHs reported functioning in a cohesive manner. Higher functioning on patient-focused team cohesion indicates that patient services were likely delivered with greater interprofessional communication and joint effort.     

Disrupted modular brain dynamics reflect cognitive dysfunction in Alzheimer's disease

The relation between pathology and cognitive dysfunction in dementia is still poorly understood, although disturbed communication between different brain regions is almost certainly involved. In this study we combine magneto-encephalography (MEG) and network analysis to investigate the role of functional sub-networks (modules) in the brain with regard to cognitive failure in Alzheimer's disease. Whole-head resting-state (MEG) was performed in 18 Alzheimer patients (age 67 ± 9, 6 females, MMSE 23 ± 5) and 18 healthy controls (age 66 ± 9, 11 females, MMSE 29 ± 1). We constructed functional brain networks based on interregional synchronization measurements, and performed graph theoretical analysis with a focus on modular organization. The overall modular strength and the number of modules changed significantly in Alzheimer patients. The parietal cortex was the most highly connected network area, but showed the strongest intramodular losses. Nonetheless, weakening of intermodular connectivity was even more outspoken, and more strongly related to cognitive impairment. The results of this study demonstrate that particularly the loss of communication between different functional brain regions reflects cognitive decline in Alzheimer's disease. These findings imply the relevance of regarding dementia as a functional network disorder.     

Behavioral variation and its consequences during incubation for American kestrels exposed to polychlorinated biphenyls

We investigated whether polychlorinated biphenyl (PCB) exposure in American kestrels (Falco sparverius) influenced incubation behavior and whether altered behavior could lead to poor reproductive success. Captive kestrels were fed a mixture of PCBs (Aroclors 1248:1254:1260) at an approximate daily dose of 7 mg/kg body weight, 1 month prior to pairing and throughout incubation. Behaviors of 23 control and 23 PCB-exposed pairs were monitored throughout incubation using an electronic balance in the nest box. PCB exposure resulted in longer incubation periods and in altered incubation behaviors. Seven of 14 behavioral variables showed some association with treatment, with sex-specific effects largely biased toward disrupted male behavior. For most behaviors, the treatment effect was explained by the delayed clutch initiation induced by PCBs rather than by a direct physiological impact of the contaminants. PCB-exposed pairs with greater attendance to their eggs and better coordination of incubation duties had improved hatching success.