Development and Evaluation of a Patient Cirrhosis Knowledge Assessment.

BACKGROUND AND AIMS: Self-management skills improve outcomes for patients with cirrhosis. While education programs exist to teach these skills, there are limited patient assessments to evaluate their efficacy. We aimed to develop and evaluate cirrhosis knowledge assessments for patients with compensated and decompensated cirrhosis. METHODS: Across two institutions, a 4-stage process was undertaken: first, we developed a comprehensive set of questions regarding cirrhosis self-management. Second, the questions underwent critical review by patients and hepatology providers. Third, patients with cirrhosis answered these questions before and after a written educational tool. Questions were updated based on results. Fourth, patients answered the updated questions before and after a video educational tool. Binomial test or paired sample t-test was used to compare pre- and post-tests depending on question type. RESULTS: In phase 3, 134 patients completed pre- and post-tests. 44% were decompensated, 81% were diagnosed with cirrhosis at least 3 years, and 52% were 60-75 years. 95% of single-answer questions were answered correctly by at least 70% of patients in the pre-test. None of the answers improved significantly with education. After phase 3, 6 questions were removed and 6 questions were edited to increase challenge. In phase 4, 96 patients (42 compensated, 54 decompensated) completed pre- and post-tests. In the compensated assessment, 3 questions improved after education and the summative score increased (7.9 to 9.0, P < 0.001). In the decompensated assessment, 4 questions improved after education and the summative score increased (7.0 to 7.7, P = 0.004). CONCLUSION: Through a rigorous process, we created and evaluated cirrhosis knowledge assessments for patients with compensated and decompensated cirrhosis. Further validation is required and then these assessments can be used to improve patient education.

Surface plasmon resonance sensor based on polarization parameter SPR imaging.

Using polarization surface plasmon resonance (SPR) imaging as a sensor has the advantage of large throughput in detection, but its sensitivity has always been inferior to other SPR sensors. The high contrast of the two polarization parameters' images related to scattering determines the high sensitivity of this new polarization SPR imaging sensor. It provides a new direction for solving the issue of low sensitivity in polarization SPR imaging. The sensor system was optimized by numerical simulation, whilst the baseline noise and sensitivity of the system were obtained by saline solution and virus detection. When the reflective index of the NaCl solution is within the range of 1.3331 to 1.36, the average sensitivity can reach 9300 RIU-1, and the maximum sensitivity can reach 13000 RIU-1. Using this new polarization SPR imaging sensor, the H1N1 virus was differentiated, showing its promising application potential within the field of biomedicine.

Baffled by NAFLD: the horse might be out of the barn but should not take us for a ride.

As awareness of nonalcoholic fatty liver disease (NAFLD) rises, it is essential to develop and implement a rigorously determined approach to identify patients who will, or will not, benefit from diagnostic evaluation.

[Short-term effectiveness comparison of unipedicular versus bipedicular percutaneous kyphoplasty for osteoporotic vertebral compression fractures with posterior wall broken].

OBJECTIVE: To compare the short-term effectiveness and safety of unipedicular versus bipedicular percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fracture (OVCF) with posterior wall broken. METHODS: The clinical data of 68 patients with OVCF with posterior wall broken and without posterior ligament complex injury and spinal cord nerve injury between June 2013 and December 2018 were retrospectively analyzed. According to the different operative approaches, the patients were divided into two groups: group A (36 cases received PKP via bilateral pedicle puncture) and group B (32 cases received PKP via unilateral pedicle paracentesis). There was no significant difference between the two groups in gender, age, fracture vertebra distribution, time from injury to operation, preoperative pain visual analogue scale (VAS) score, Oswestry disability index (ODI), and height of injured vertebra ( P>0.05). The operation time, intraoperative fluoroscopy times, and bone cement volume were recorded and compared between the two groups. The VAS score and ODI score were used to evaluate the effectiveness before operation, at 1 day and 6 months after operation; the height of injured vertebra was measured on the lateral X-ray film, and the recovery height of injured vertebra at 1 day after operation and the loss height of injured vertebra at 6 months after operation were calculated; the intraoperative and postoperative complications of the two groups were recorded. RESULTS: The operation time, intraoperative fluoroscopy times, and bone cement volume of group B were significantly less than those of group A ( P<0.05). All patients were followed up 10-35 months, with an average of 18 months. During the operation, there were 2 cases (5.56%) of cement leakage in group A and 9 cases (28.13%) in group B, showing significant difference ( χ 2=4.808, P=0.028). There was no adverse reactions of bone cement, iatrogenic spinal cord injury, infection of puncture port, or other complications in the two groups. During the follow-up period, there were 3 cases (8.3%) of adjacent vertebral fractures in group A and 2 cases (6.3%) in group B, showing no significant difference between the two groups ( χ 2=0.027, P=0.869). The height of injured vertebra of the two groups at 1 day and 6 months after operation were significantly improved when compared with preoperative ones ( P<0.05). There was no significant difference in the height of injured vertebrae and the recovery height of injured vertebra at 1 day after operation between the two groups ( P>0.05). However, at 6 months after operation, the height of injured vertebra in group B was significantly lower than that in group A ( P<0.05), and the loss height of injured vertebra in group B was significantly higher than that in group A ( P<0.05). The VAS score and ODI score at 1 day and 6 months after operation were significantly improved when compared with preoperative ones in both groups ( P<0.05), but there was no significant difference between the two groups ( P>0.05). CONCLUSION: Both bipedicular and unipedicular PKP can obtain satisfactory effectiveness for the treatment of OVCF with posterior wall broken, but the former may have advantages of lower cement leakage rate and less height loss.

Suppressive myeloid cells are expanded by biliary tract cancer-derived cytokines in vitro and associate with aggressive disease.

BACKGROUND: BTC is an aggressive disease exacerbated by inflammation and immune suppression. Expansion of immunosuppressive cells occurs in biliary tract cancer (BTC), yet the role of BTC-derived cytokines in this process is unclear. METHODS: Activated signalling pathways and cytokine production were evaluated in a panel of human BTC cell lines. Human peripheral blood mononuclear cells (PBMCs) were cultured with BTC supernatants, with and without cytokine neutralising antibodies, and analysed by flow cytometry or immunoblot. A human BTC tissue microarray (TMA, n = 69) was stained for IL-6, GM-CSF, and CD33+S100a9+ cells and correlated with clinical outcomes. RESULTS: Immunomodulatory factors (IL-6, GM-CSF, MCP-1) were present in BTC supernatants. BTC supernatants expanded CD33dimCD11b+HLA-DRlow/- myeloid-derived suppressor cells (MDSCs) from human PBMCs. Neutralisation of IL-6 and GM-CSF in BTC supernatants inhibited activation of STAT3/5, respectively, in PBMCs, with heterogeneous effects on MDSC expansion in vitro. Staining of a BTC TMA revealed a positive correlation between IL-6 and GM-CSF, with each cytokine and more CD33+S100a9+ cells. Increased CD33+S100a9+ staining positively correlated with higher tumour grade, differentiation and the presence of satellite lesions. CONCLUSION: BTC-derived factors promote suppressive myeloid cell expansion, and higher numbers of CD33+S100a9+ cells in resectable BTC tumours correlates with more aggressive disease.

Promising therapeutics of gastrointestinal cancers in clinical trials.

Many novel therapeutics are being developed for patients with cancers along the gastrointestinal (GI) tract. These emerging agents are frequently classified by their biological targets such as tumor growth pathways, tumor metabolism, microenvironment, etc. Some agents targeting cancer growth pathways are based on existing clinically validated therapeutic targets, such as regorafenib for hepatocellular carcinoma (HCC), while other agents focus on newly identified targets, such as FGFR fusions in cholangiocarcinoma. Drugs modifying the immunosuppressive tumor microenvironment have emerged as an attractive area of clinical investigation. Moreover, drugs targeting the stem-cell like qualities of cancer and the tight junction protein claudin 18.2 have generated quite a lot of excitement in the field. In this paper, we will systemically review the recent promising agents and therapeutic strategies in GI cancers.

[Effect of functional exercise at different time and different immobilization positions on functional recovery of elbow joint with type C distal humeral fractures].

Objective: To investigate the effect of functional exercises at different time and different immobilization positions on the functional recovery of elbow joint with type C distal humeral fractures. Methods: A total of 120 patients with type C distal humeral fractures admitted to the hospital between June 2013 and July 2015 were included in the study. They were randomly allocated to 3 groups, 40 patients in each group. Group A: functional exercises began immediately after the operation; Group B: the affected elbow was fixed at 90° flexion for 1 week and then began functional exercises after 1 week of immobilization; Group C: the affected elbow was fixed at 30° extension for 1 week and then began functional exercises after 1 week of immobilization. There was no significant difference in gender, age, fracture pattern, fracture side, injury time, and surgical approach between groups ( P>0.05). Results: In groups A and B, 1 case had incision redness and swelling respectively, and the other incisions healed by first intention. Five patients occurred myositis ossificans in group A, 4 cases in group B, and 5 cases in group C. The incidence of complications in groups A, B, and C was 15.0% (6/40), 12.5% (5/40), and 12.5% (5/40), respectively. There was no significant difference between groups ( χ2=0.144, P=0.930). All patients were followed up 6-25 months, with an average of 9.8 months. At 2 weeks after operation, the Mayo elbow joint function score of group A was significantly higher than those of groups B and C ( P<0.05), and the visual analogue scale (VAS) of group A was significantly lower than those of groups B and C ( P<0.05). There was no significant difference between groups B and C ( P>0.05). At 6 months after operation, there was no significant difference in Mayo elbow joint function score and VAS score between groups ( P>0.05). At 2 weeks and 6 months after operation, the flexion and extension activities of elbow joint in groups A and C were better than that in group B ( P<0.05), and there was no significant difference between groups A and C ( P>0.05). There was no significant difference in forearm rotation between groups ( P>0.05). All fractures of 3 groups achieved clinical healing, and there was no significant difference in healing time between groups ( P>0.05). Conclusion: Early functional exercises can relieve pain and obtain better elbow flexion and extesion activities after operation. The elbow joint fixed at 30° extension is better than at 90° flexion in elbow flexion and extension activitis.

Dual Inhibition of MEK and PI3K/Akt Rescues Cancer Cachexia through both Tumor-Extrinsic and -Intrinsic Activities.

Involuntary weight loss, a part of the cachexia syndrome, is a debilitating comorbidity of cancer and currently has no treatment options. Results from a recent clinical trial at our institution showed that biliary tract cancer patients treated with a MEK inhibitor exhibited poor tumor responses but surprisingly gained weight and increased their skeletal muscle mass. This implied that MEK inhibition might be anticachectic. To test this potential effect of MEK inhibition, we utilized the established Colon-26 model of cancer cachexia and the MEK1/2 inhibitor MEK162. Results showed that MEK inhibition effectively prevented muscle wasting. Importantly, MEK162 retained its ability to spare muscle loss even in mice bearing a Colon-26 clone resistant to the MEK inhibitor, demonstrating that the effects of blocking MEK are at least in part independent of the tumor. Because single-agent MEK inhibitors have been limited as a first-line targeted therapy due to compensatory activation of other oncogenic signaling pathways, we combined MEK162 with the PI3K/Akt inhibitor buparlisib. Results showed that this combinatorial treatment significantly reduced tumor growth due to a direct activity on Colon-26 tumor cells in vitro and in vivo, while also preserving skeletal muscle mass. Together, our results suggest that as a monotherapy, MEK inhibition preserves muscle mass, but when combined with a PI3K/Akt inhibitor exhibits potent antitumor activity. Thus, combinatorial therapy might serve as a new approach for the treatment of cancer cachexia. Mol Cancer Ther; 16(2); 344-56. ©2016 AACRSee related article by Kobayashi et al., p. 357.

Up-regulated expression of peroxisome proliferator-activated receptor gamma in the hypothalamic-pituitary-adrenal axis of weaned pigs after Escherichia coli lipopolysaccharide challenge.

The expression of peroxisome proliferator-activated receptor gamma (PPARgamma) was investigated in the hypothalamic-pituitary-adrenal (HPA) axis of weaned pigs after injection with 100 microg/kg bodyweight Escherichia coli lipopolysaccharide (LPS) (n=6) and control pigs injected with sterile saline (n=6). LPS increased PPARgamma mRNA and protein expression in the hypothalamus (23.8 and 3.1-fold relative to controls, respectively), pituitary gland (9.2 and 2.0-fold, respectively) and adrenal gland (3.5 and 2.3-fold, respectively) (P<0.05). LPS also induced an increase in PPARgamma immunohistochemical staining in the hypothalamus (1.3-fold), adenohypophysis (1.3-fold), adrenal cortex (1.4-fold) and adrenal medulla (1.6-fold) (P<0.05). Concurrent with up-regulated expression of PPARgamma, LPS increased the concentrations of plasma corticotrophin-releasing hormone (2.1-fold) and adrenocorticotrophin (1.4-fold) (P<0.05). LPS also induced elevations of interleukin 6 and tumour necrosis factor alpha mRNA levels in the hypothalamus (4.0 and 3.2-fold, respectively), pituitary gland (20.7 and 5.1-fold, respectively) and adrenal gland (3.9 and 3.3-fold, respectively) (P<0.05). PPARgamma may play a role in the regulation of neuroendocrine responses associated with immunological stress in pigs.

Mechanisms of growth arrest by zinc ribbon domain-containing 1 in gastric cancer cells.

Previous studies by our laboratory indicated that zinc ribbon domain-containing 1 (ZNRD1) suppressed the growth of gastric cancer cells with a G(1) cell cycle arrest. However, the precise molecular mechanism underlying the growth-inhibitory effect of ZNRD1 remained fragmentary. In the present study, we have demonstrated that ZNRD1 could significantly inhibit the in vitro and in vivo growth of gastric cell line MKN28. Human cDNA microarray, reverse transcription-polymerase chain reaction and western blot analyses were used to identify differentially expressed cell cycle-related genes in MKN28 cells over-expressing ZNRD1. ZNRD1-induced growth suppression was found at least partially to regulate various proteins and signaling pathways controlling G(1) to S progression, including inhibition of cyclin D1 and CDK4, up-regulation of p21(CIP1/WAF1) and p27(Kip1) and acceleration of pRb dephosphorylation. Furthermore, ZNRD1 significantly inhibited the transcriptional activity of cyclin D1. p27(Kip1) might play a pivotal role in ZNRD1-induced cell cycle arrest because the p27(Kip1) anti-sense could block the cytostatic effects of ZNRD1. Moreover, ZNRD1 suppressed Skp2 expression via an increase in the protein instability, and induced significant decrease in cyclin E-CDK2 kinase activity. In addition, ZNRD1 could reduce tumor microvessel densities through inhibition of VEGF. Taken together, these results suggested that ZNRD1 might inhibit cell growth by targeting cell cycle-related genes and reducing tumor angiogenesis.