Covert hepatic encephalopathy is associated with aggressive disease progression and poor survival in patients with cirrhosis.

OBJECTIVES: Covert hepatic encephalopathy (CHE) negatively affects the health-related quality of life and increases the risk of overt HE (OHE) in patients with liver cirrhosis. However, the impact of CHE on long-term patient outcomes remains controversial. This study aimed to explore the association between CHE and disease progression and survival among cirrhotic patients. METHODS: This was a single-center prospective study that enrolled 132 hospitalized patients with cirrhosis, with an average follow-up period of 45.02 ± 23.06 months. CHE was diagnosed using the validated Chinese standardized psychometric hepatic encephalopathy score. RESULTS: CHE was detected in 35.61% cirrhotic patients. During the follow-up, patients with CHE had a higher risk of developing OHE (log-rank 5.840, P = 0.016), exacerbation of ascites (log-rank 4.789, P = 0.029), and portal vein thrombosis (PVT) (log-rank 8.738, P = 0.003). Cox multivariate regression analyses revealed that CHE was independently associated with the occurrence of OHE, exacerbation of ascites, and PVT. Furthermore, patients with progression of cirrhosis were more likely to be diagnosed as CHE (log-rank 4.462, P = 0.035). At the end of the follow-up, patients with CHE had a lower survival rate compared to those without CHE (log-rank 8.151, P = 0.004). CHE diagnosis (hazard ratio 2.530, P = 0.008), together with elder age and higher Child-Pugh score, were risk factors for impaired survival in cirrhotic patients. CONCLUSION: CHE is associated with disease progression and poor survival in patients with cirrhosis, indicating that CHE may serve as an independent predictor of poor prognosis among these patients.

The predictive value of peripheral blood cells and lymphocyte subsets in oesophageal squamous cell cancer patients with neoadjuvant chemoradiotherapy.

Purpose: Neoadjuvant chemoradiotherapy (nCRT) is a standard treatment option for patients with stage III oesophageal cancer. Approximately 30% of oesophageal cancer patients will have a pathological complete response (pCR) after nCRT. However, available clinical methods cannot accurately predict pCR for patients. We aimed to find more indicators that could be used to predict the pathological response to nCRT. Method: A total of 84 patients with stage III oesophageal squamous cell cancer were enrolled in this study. Ten patients failed to have surgery as a result of progressive disease (PD). Among the patients who underwent surgery, 32 patients had a pathologic complete response (pCR), whereas 42 patients showed no or partial response (npCR) after nCRT. Routine blood test results and lymphocyte subset assessments before and after nCRT were retrospectively analysed. Univariate and multivariate analyses were used to identify independent predictors of the clinical curative effect of nCRT. Eventually, nomograms were established for predicting the PD and pCR rates. Results: The numbers of lymphocytes, B lymphocytes, T lymphocytes, Th lymphocytes, Ts lymphocytes, and NK cells and the percentages of B lymphocytes and NK cells were decreased significantly after nCRT (P < 0.0001), whereas the percentages of T lymphocytes and Ts lymphocytes increased (P < 0.0001). Univariate analysis showed that age, the length of the lesion, the level of haemoglobin before nCRT, and the amount of change in haemoglobin were related to PD, and the percentage of NK cells after nCRT was related to pCR. Multivariate logistic analysis demonstrated that the length of the lesion, the neutrophil-to-lymphocyte ratio (NLR) before nCRT, and the amount of change in haemoglobin were independent predictors of PD, whereas the percentage of NK cells after nCRT was an independent predictor of pCR. Conclusion: Lymphocyte subsets changed dramatically during nCRT, and these changes together with baseline and posttreatment lymphocyte subsets have predictive value in determining the response to nCRT for oesophageal cancer.

Case Report: A Case of Concomitant Paroxysmal Kinesigenic Dyskinesia and Epilepsy: Can We Treat Two Birds With One Stone?

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent episodes of movement-induced motor attacks. PKD patients may have concomitant epilepsy. Differentiation between the two disorders and effective control of both diseases remain challenging. CASE PRESENTATION: We present a Chinese girl with typical manifestations of PKD, who also suffered from generalized tonic-clonic seizure attacks at the same time. Genetic testing confirmed a PRRT2 mutation (c.649dupC). Oxcarbazepine was initially used, but withdrawn due to a hypersensitivity reaction. Levetiracetam was initiated afterwards, which was effective for seizures but failed to control her PKD symptoms. The addition of lacosamide (LCM) completely controlled her PKD symptoms. CONCLUSION: This is the first case reporting the effectiveness of LCM for concomitant PKD and epilepsy. Our case proposes a novel alternative for such patients who are resistant or cannot tolerate conventional anti-sodium antiepileptics.

Clerodane diterpenoids from Dodonaea viscosa and their inhibitory effects on ATP citrate lyase.

Six undescribed clerodane diterpenoids, dodovisins A-F, together with nine known ones, were isolated from the aerial parts of Dodonaea viscosa (L.) Jacq. Their structures were elucidated by extensive spectroscopic techniques, X-ray crystallographic analysis, and ECD calculation. Dodovisins A and B possess a rare carbon skeleton featuring a bicyclo[6.2.0]decane motif. Dodovisins C-E represent the first clerodane diterpenoids with a 4(5 â†’ 19)-abeo-2,4,10(1)-triene moiety. Dodovisins A, E, and strictic acid showed potent inhibitory activities against ATP citrate lyase.

Improving the ability to predict hospital mortality among adults by combining two status epilepticus outcome scoring tools.

OBJECTIVE: The goal of this study was to compare the predictive ability of the Status Epilepticus Severity Score (STESS), the Encephalitis-nonconvulsive status epilepticus (NCSE)-Diazepam resistance-Image abnormalities-Tracheal intubation (END-IT), and the combination of these two scoring tools to predict mortality among inhospital patients with status epilepticus (SE). METHODS: A retrospective analysis was conducted of adult patients with SE who were admitted to the neurology department, the emergency department, and the intensive care unit from January 2013 to December 2017. The patients were divided into two groups: survivors and nonsurvivors. The STESS data were obtained when the patient arrived at the hospital, and the END-IT data were collected 24 h after patients were initially treated in the hospital. The ability of the scoring tools to predict death in patients with SE, alone or in combination, was evaluated. RESULTS: A total of 123 patients with SE were included in the study, of which 22 died, for a mortality rate of 17.9%. The STESS and END-IT scores of nonsurvivors were both significantly higher than those of survivors (median STESS 4 vs. 2, p = 0.003; median END-IT 3 vs. 1, p < 0.001). The area under the receiver operating characteristic curve (AUC) was 0.698 for the STESS and 0.852 for the END-IT, and the cutoff values were 4 and 3, respectively. The AUC of the END-IT with the optimal cutoff value was larger than that of the STESS (p = 0.024). The sensitivity and specificity of combining the STESS and END-IT by the serial method (STESS ≥ 4∩END-IT ≥ 3) were 0.50 and 0.95, respectively, and the specificity was significantly higher than the STESS or END-IT (both p's < 0.001). The sensitivity and specificity of combining the STESS and END-IT by the parallel method (STESS ≥ 4⋃END-IT ≥ 3) were 0.91 and 0.53, respectively, and the sensitivity was higher than the STESS was (p = 0.016). CONCLUSION: Our results indicated that the combined score of the STESS and END-IT systems was a better predictor of survival of patients with SE than the scores of either the STESS system or the END-IT system alone and that combining the scores may be considered to be a new method for early identification of patients for both good and bad outcomes.

Prevalence and risk factors for gallstone disease: A population-based cross-sectional study.

OBJECTIVE: To explore the prevalence of and risk factors for gallstone disease in Shanghai, China. METHODS: A population-based cross-sectional study was conducted in Shanghai between 2016 and 2017. Using a three-stage stratified sampling strategy, 4009 participants (1753 men and 2256 women) from 10 districts were enrolled. RESULTS: The overall prevalence of gallstones was 6.83% (6.22% for men vs 7.31% for women, P = 0.173). According to the multivariate analysis, individuals aged ≥40 years (odds ratio [OR] 3.058, 95% confidence interval [CI] 2.110-4.433, P < 0.001), hypertension (OR 1.479, 95% CI 1.076-2.034, P = 0.016), thyroid disease (OR 1.409, 95% CI 1.029-1.928, P = 0.032), a family history of gallstones (OR 2.234, 95% CI 1.362-3.662, P = 0.001) and a waist-to-height ratio ≥0.5 (OR 1.656, 95% CI 1.197-2.292, P = 0.002) had an increased risk of developing gallstones. The risk of gallstone disease was 2.232 (95% CI 1.167-4.268, P = 0.015) times higher in individuals with elevated C4 levels than in those with normal C4 levels. Diabetes (OR 4.144, 95% CI 1.171-14.671, P = 0.028) was a risk factor for the formation of gallstones with diameters ≥1 cm, and men were more susceptible to develop multiple stones (OR 2.356, 95% CI 1.321-4.200, P = 0.004). CONCLUSION: Individuals aged ≥40 years, with a history of hypertension and familial gallstones, a high waist-to-height ratio, thyroid disease and high C4 levels were related to an increased risk of gallstone disease.

MRI-based radiomics model for preoperative prediction of 5-year survival in patients with hepatocellular carcinoma.

BACKGROUND: Recurrence is the major cause of mortality in patients with resected HCC. However, without a standard approach to evaluate prognosis, it is difficult to select candidates for additional therapy. METHODS: A total of 201 patients with HCC who were followed up for at least 5 years after curative hepatectomy were enrolled in this retrospective, multicentre study. A total of 3144 radiomics features were extracted from preoperative MRI. The random forest method was used for radiomics signature building, and five-fold cross-validation was applied. A radiomics model incorporating the radiomics signature and clinical risk factors was developed. RESULTS: Patients were divided into survivor (n = 97) and non-survivor (n = 104) groups based on the 5-year survival after surgery. The 30 most survival-related radiomics features were selected for the radiomics signature. Preoperative AFP and AST were integrated into the model as independent clinical risk factors. The model demonstrated good calibration and satisfactory discrimination, with a mean AUC of 0.9804 and 0.7578 in the training and validation sets, respectively. CONCLUSIONS: This radiomics model is a valid method to predict 5-year survival in patients with HCC and may be used to identify patients for clinical trials of perioperative therapies and for additional surveillance.

Combined Scores from the EncephalApp Stroop Test, Number Connection Test B, and Serial Dotting Test Accurately Identify Patients With Covert Hepatic Encephalopathy.

BACKGROUND & AIMS: The EncephalApp Stroop test is a high-sensitivity but low-specificity test that has been used to identify patients with covert hepatic encephalopathy (CHE). We aimed to develop a new strategy to detect CHE, combining EncephalApp Stroop test score with scores from subtests of the psychometric hepatic encephalopathy scoring system (PHES). METHODS: We performed a survey of 569 adult volunteers (229 men) in 9 communities in Shanghai, China, administering the EncephalApp Stroop test to determine the range of scores in the general population. Data from the standard PHES, including the number connection test-A, number connection test-B (NCT-B), line tracing test, serial dotting test (SDT), and digit symbol test, were used as the reference standard for diagnosis of CHE. A combination of the EncephalApp Stroop with subtests of the PHES was used to establish a new strategy for CHE diagnosis. We validated our findings using data from 160 patients with cirrhosis from 5 centers China. RESULTS: We determined the range of EncephalApp Stroop test scores for the volunteers of different decades of age, education levels, and sexes. Age, education level, and sex were independently associated with EncephalApp Stroop test scores. A combination of scores from the EncephalApp Stroop test, the NCT-B, and the SDT identified patients with CHE with the highest level of accuracy, when the standard PHES was used as the reference standard. A combination of scores of 187 sec for the EncephalApp Stroop test and below -1 for the NCT-B or below -1 for the SDT identified patients with CHE with an area under the curve (AUC) of 0.86, 81.0% sensitivity, and 91.9% specificity, and 87.5% accuracy. In the validation cohort, these cutoff scores identified patients with CHE with an AUC of 0.88, 97.1% sensitivity, 79.3% specificity, and 86.9% accuracy. The average time to calculate this score was 374±140 sec, compared 424±115 sec for the entire PHES. CONCLUSION: Scores from the EncephalApp Stroop test, NCT-B, and SDT identify patients with CHE with approximately 87% accuracy, and in a much shorter time than the standard PHES. This score combination could be a valid and convenient method for identifying patients with CHE. chictr.org.cn number, ChiCTR-EDC-17012007, ChiCTR1800019954.

Vistriterpenoids A and B, Two New 24-Nor-oleanane Triterpenoids from Dodonaea viscosa.

Two new triterpenoids, vistriterpenoids A (1) and B (2), and four known ones, were acquired from Dodonaea viscosa. Compounds 1 and 2 represent the 24-nor-oleanane triterpenoids isolated from the genus Dodonaea for the first time. Their structures were identified based on extensive spectroscopic methods. Compounds 1, 2, 5, and 6 exerted inhibitory activities against PTP1B in vitro.

Identification of Newly Diagnosed Diabetes and Prediabetes Using Fasting Plasma Glucose and Urinary Glucose in a Chinese Population: A Multicenter Cross-Sectional Study.

BACKGROUND: Although fasting plasma glucose (FPG) has been highly recommended as the sole test for diabetes screening, the efficacy of FPG alone for diabetes screening is potentially limited due to its low sensitivity. The aim of this study was to improve the efficacy of FPG for diabetes screening using urinary glucose (UG). METHODS: This study was initiated on November 12, 2015, and ended on June 28, 2016. A representative sample of individuals aged between 18 and 65 years, with no history of diabetes, from 6 cities in Jiangsu Province participated in this study. A 75-g oral glucose tolerance test was used to diagnose diabetes. All urine samples were collected within 2 h of oral glucose loading to measure UG. Partial correlation analyses were used to evaluate the associations between UG and other glycemic variables, including FPG, 2-h plasma glucose (2h-PG), and glycated hemoglobin A1c, after adjustment for age. The performance of UG was evaluated using a receiver operating characteristic (ROC) curve analysis. RESULTS: Of the 7485 individuals included, 8% were newly diagnosed with diabetes and 48.7% had prediabetes. The areas under the ROC curves for UG were 0.75 for estimation of 2h-PG ≥7.8 mmol/L and 0.90 for 2h-PG ≥11.1 mmol/L, respectively. The sensitivity and specificity of UG were 52.3% and 87.8%, respectively, for 2h-PG ≥7.8 mmol/L (cutoff point ≥130 mg), and 83.5% and 87.5%, respectively, for 2h-PG ≥11.1 mmol/L (cutoff point ≥178.5 mg). The combination of FPG and UG demonstrated a significantly higher sensitivity than that of FPG alone for the identification of diabetes ([483/597] 80.9% vs. [335/597] 56.1%, χ2 = 85.0, P < 0.001) and glucose abnormalities ([2643/4242] 62.3% vs. [2365/4242] 55.8%, χ2 = 37.7, P < 0.001). CONCLUSIONS: The combination of UG and FPG substantially improves the efficacy of using FPG alone for diabetes screening; this combination might be a practical screening tool and is worth being recommended in the future.

Ketogenic diet attenuates neuronal injury via autophagy and mitochondrial pathways in pentylenetetrazol-kindled seizures.

Autophagy alterations have been observed in a variety of neurological disorders, however, very few studies have focused on autophagy alterations in epilepsy. The ketogenic diet (KD) likely ameliorates neuronal loss in several seizure models. However, whether this neuroprotective function occurs via starvation-induced autophagy and its prevalence in chronic kindled seizures remains unknown. The aim of this study was to determine the role of autophagy following seizure under KD, and the potential mechanism involved. Pentylenetetrazol (PTZ)-kindled rats, which were fed a Normal diet (ND) or KD, were pretreated with intraventricular infusions of saline, autophagy inducer rapamycin (RAP), or inhibitor 3-methyladenine (3-MA). KD alleviated seizure severity, decreased the number of Fluoro-jade B (FJB)-positive cells in the hippocampus of kindled rats. These effects were abolished by 3-MA pretreatment. RAP pretreatment did not affect seizure severity, but decreased the number of FJB-positive cells in ND group. KD decreased the percentage of damaged mitochondria in kindled group. Hippocampal Beclin-1 was increased by KD in vehicle group. The autophagy proteins Atg5, Beclin-1 and the ratio of microtubule-associated protein 1 light chain 3 (LC3) II to LC3-I in kindled KD-fed rats were higher, and the autophagy substrate P62 was lower than those in the kindled ND-fed rats, indicating an increase in autophagy following KD. Pretreatment with RAP increased the level of LC3-II/LC3-I, and pretreatment with 3-MA increased the level of P62 in KD-fed rats. To further clarify the mechanism of autophagy protection, the levels of key mitochondria related molecules were examed. The results showed that mitochondrial cytochrome c was up-regulated, cytosolic cytochrome c and the downstream cleaved caspase-3 was down-regulated in KD-fed rats, indicating a decrease in mitochondrial apoptosis. Taken together, our results indicated that KD activates autophagic pathways and reduces brain injury during PTZ-kindled seizures. The neuroprotective effect of KD is likely exerted via a reduction of mitochondrial cytochrome c release.

Small intestinal hemangioma: Endoscopic or surgical intervention? A case report and review of literature.

BACKGROUND: Hemangioma of the small intestine is a rare vascular malformation. Before the advent of capsule endoscopy (CE) and balloon-assisted enteroscopy (BAE), preoperative diagnosis of this disease was extremely difficult. CASE SUMMARY: In this study, we report a 24-year-old female with a large transmural small bowel cavernous hemangioma, which was diagnosed with CE and BAE preoperatively and removed successfully using minimally invasive surgery. Meanwhile, we perform a literature review of the studies about intestinal hemangiomas published after 2000. Literature review revealed that 91.9% of the lesions were diagnosed preoperatively by CE and/or BAE and 45.9% of them were treated endoscopically, which is a marked improvement compared to before 2000. Therefore, CE and BAE are useful modalities for the preoperative diagnosis of hemangiomas in the small intestine. CONCLUSION: Endoscopic treatment of intestinal hemangioma is generally prudent and might be suitable for multiple, relatively small lesions.

Rosuvastatin inhibits the smooth muscle cell proliferation by targeting TNFα mediated Rho kinase pathway.

OBJECTIVE: To investigate whether Tumor Necrosis Factor-alpha (TNFα) is capable of activating Rho kinase pathway which leads to smooth muscle cell proliferation and the intervention function of Rosuvastatin, and clarify the mechanism and intervention manner of anti-atherosclerosis by Rosuvastatin. METHODS: Wistar neonate rat smooth muscle cells were cultured, and the activity of cell proliferation was determined by methyl thiazolyl tetrazolium (MTT). The expression of Rho kinase genes after the stimulation of TNFα was evaluated by RT-PCR. Western blot method was used to measure the protein expression of proliferating cell nuclear antigen (PCNA) after TNFα stimulation and Rosuvastatin intervention in smooth muscle cell. RESULTS: The TNFα stimulation significantly enhanced the expression of Rho kinase and increased the expression of PCNA protein in smooth muscle cells (P < 0.05). These effects were positively correlated with prolonged treatment whereas additional Rosuvastatin administration inhibited the above-mentioned effects (P < 0.05). CONCLUSIONS: The activation of TNFα mediated Rho kinase signaling pathway can significantly promote smooth muscle cell proliferation, and Rosuvastatin can not only inhibit this pathway but also the induced proliferation.

[Clinical therapeutic effect of esophageal carcinoma with hand video assisted surgery].

OBJECTIVE: To explore the clinical therapeutic effect of esophageal carcinoma with hand video assisted surgery. METHODS: Forty cases which C TNM stage was T3N1M0 received hand video assisted surgery (HVATS group), 40 cases received routine operation (control group). Recurrence survival analysis of each group was analyzed with SPSS10.0 software according to the date of the stage and survival rate. RESULTS: All group have satisfied surgical result. All patients have good quality of life. The 3 year survival rate was 52.7% in HVATS group and 51.3% in control group. The difference of survival rate was no significance. CONCLUSION: Hand video assisted surgery for esophageal carcinoma had same result as routine thoracic operation. Short operation time, less trauma and fast recovery are the advantages of hand video assisted surgery.

[Clinical value of videomediastinoscopy in diagnosis of mediastinal disease].

OBJECTIVE: To evaluate the role of videomediastinoscopy in the diagnosis of disease of the mediastinum. METHODS: We retrospectively reviewed the clinical records of the 115 patients who underwent videomediastinoscopy. Local anesthesia or general anesthesia was employed. This operation consisted of cervical videomediastinoscopy in 102 patients, parasternal videomediastinoscopy in 13 patients, ninety-one patients had videomediastinoscopy for diagnosis of isolated mediastinal mass or lymphadenopathy, 25 patients with non small cell lung cancer or suspected lung cancer showed enlarged mediastinal lymph nodes radiographically in the chest. RESULTS: Among the patients with mediastinal disease, sarcoidosis was diagnosed in 37 patients, tuberculosis in 14 patients, lymphoma in 15 patients, nodal metastasis in 18 patients, noncaseating granulomata without classical "sarcoid" in 6 patients, with the accuracy of 93.3% (84/90); and staging of lung cancer in 25 patients, with the accuracy of 100% (25/25). The total accuracy of videomediastinoscoy and CT was 94.8% (109/115), 56.5% (65/115), respectively. Mean operative time was 26 min. There was neither complication nor mortality. CONCLUSION: videomediastinoscopy is a safe and effective procedure for the diagnosis of mediastinal disease and the staging of lung cancer.

[Resection for lung cancer invading the superior vena cava].

OBJECTIVE: To analyze the feasibility and the value of resection for lung cancer invading the superior vena cava (SVC). METHODS: Between 1988 and 2005 the data of 31 patients who underwent resection were analyzed retrospectively. The reconstruction was done using simple suture, pericardial patch or prosthetic replacement. Postoperative morbidity, long-term survival were examined using the Kaplan-Meier method (Log rank test) and the COX model for survival. RESULTS: Seventeen squamous cell carcinomas, 8 adenocarcinomas, and 6 undifferentiated small cell carcinomas were resected. There were 13 partial SVC resection, the reconstruction was done using a simple running in 5 patients, and a pericardial patch in 8 patients. Eighteen patients underwent complete resection of SVC with prosthetic replacement. The time of clamping the SVC system was from 8 to 35 minutes for complete resection patients, while the time was from 3 to 15 minutes for partial resection patients. One patient didn't clamp the SVC. Postoperative morbidity and mortality were 48% and 0%, respectively. One, 3 and 5-year survival rates were 61%, 33% and 21%, respectively, with median survival at 31 months. Survival rate of patients with N2 disease was obviously lower than those with localized (N0/N1) nodal disease (chi2 = 14.3, P = 0.000), the median survival was 42 and 13 months respectively. There were no significant effects on overall survival with pathologic features and surgery methods. Survival rate of patients with induction chemotherapy before operation or intraoperative chemotherapy was higher than those received direct surgery (chi2 = 5.0, P = 0.025), the median survival was 39 and 14 months respectively. CONCLUSIONS: The resection of the SVC for involvement by lung cancer can be performed in selected patients, especially for those with localized (N0/N1) nodal disease. Induction chemotherapy should be performed.