Effect of Opioids on All-cause Mortality and Opioid Addiction in Total Hip Arthroplasty: a Korea Nationwide Cohort Study.

BACKGROUND: The purpose of this study was to investigate the use of opioids before and after total hip arthroplasty (THA), to find out the effect of opioid use on mortality in patients with THA, and to analyze whether preoperative opioid use is a risk factor for sustained opioid use after surgery using Korean nationwide cohort data. METHODS: This retrospective nationwide study identified subjects from the Korean National Health Insurance Service-Sample cohort (NHIS-Sample) compiled by the Korean NHIS. The index date (time zero) was defined as 90 days after an admission to a hospital to fulfill the eligibility criteria of the THA. RESULTS: In the comparison of death risk according to current use and the defined daily dose of tramadol and strong opioids in each patient group according to past opioid use, there were no statistically significant differences in the adjusted hazard ratio for death compared to the current non-users in all groups (P > 0.05). Past tramadol and strong opioid use in current users increased the risk of the sustained use of tramadol and strong opioids 1.45-fold (adjusted rate ratio [aRR]; 95% confidence interval [CI], 1.12-1.87; P = 0.004) and 1.65-fold (aRR; 95% CI, 1.43-1.91; P < 0.001), respectively, compared to past non-users. CONCLUSION: In THA patients, the use of opioids within 6 months before surgery and within 3 months after surgery does not affect postoperative mortality, but a past-use history of opioid is a risk factor for sustained opioid use. Even after THA, the use of strong opioids is observed to increase compared to before surgery.

Relationship Between Cognitive Function and Dysphagia After Stroke.

OBJECTIVE: To investigate the characteristics of cognitive deficits in patients with post-stroke dysphagia, and to analyze the relationships between cognitive dysfunction and severity of dysphagia in supratentorial stroke. METHODS: A total of 55 patients with first-ever supratentorial lesion stroke were enrolled retrospectively, within 3 months of onset. We rated dysphagia from 0 (normal) to 4 (severe) using the dysphagia severity scale (DSS) through clinical examinations and videofluoroscopic swallowing studies (VFSS). The subjects were classified either as non-dysphagic (scale 0) or dysphagic (scale 1 to 4). We compared general characteristics, stroke severity and the functional scores of the two groups. We then performed comprehensive cognitive function tests and investigated the differences in cognitive performance between the two groups, and analyzed the correlation between cognitive test scores, DSS, and parameters of oral and pharyngeal phase. RESULTS: Fugl-Meyer motor assessment, the Berg Balance Scale, and the Korean version of the Modified Barthel Index showed significant differences between the two groups. Cognitive test scores for the dysphagia group were significantly lower than the non-dysphagia group. Significant correlations were shown between dysphagia severity and certain cognitive subtest scores: visual span backward (p=0.039), trail making tests A (p=0.042) and B (p=0.002), and Raven progressive matrices (p=0.002). The presence of dysphagia was also significantly correlated with cognitive subtests, in particular for visual attention and executive attention (odds ratio [OR]=1.009; 95% confidence interval [CI], 1.002-1.016; p=0.017). Parameters of premature loss were also significantly correlated with the same subtests (OR=1.009; 95% CI, 1.002-1.016; p=0.017). CONCLUSION: Our results suggest that cognitive function is associated with the presence and severity of post-stroke dysphagia. Above all, visual attention and executive functions may have meaningful influence on the oral phase of swallowing in stroke patients with supratentorial lesions.

Degradation of Kidney and Psoas Muscle Proteins as Indicators of Post-Mortem Interval in a Rat Model, with Use of Lateral Flow Technology.

We investigated potential protein markers of post-mortem interval (PMI) using rat kidney and psoas muscle. Tissue samples were taken at 12 h intervals for up to 96 h after death by suffocation. Expression levels of eight soluble proteins were analyzed by Western blotting. Degradation patterns of selected proteins were clearly divided into three groups: short-term, mid-term, and long-term PMI markers based on the half maximum intensity of intact protein expression. In kidney, glycogen synthase (GS) and glycogen synthase kinase-3ß were degraded completely within 48 h making them short-term PMI markers. AMP-activated protein kinase α, caspase 3 and GS were short-term PMI markers in psoas muscle. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was a mid-term PMI marker in both tissues. Expression levels of the typical long-term PMI markers, p53 and ß-catenin, were constant for at least 96 h post-mortem in both tissues. The degradation patterns of GS and caspase-3 were verified by immunohistochemistry in both tissues. GAPDH was chosen as a test PMI protein to perform a lateral flow assay (LFA). The presence of recombinant GAPDH was clearly detected in LFA and quantified in a concentration-dependent manner. These results suggest that LFA might be used to estimate PMI at a crime scene.

Relationship of Vascular Factors on Electrophysiologic Severity of Diabetic Neuropathy.

OBJECTIVE: To investigate the impact of vascular factors on the electrophysiologic severity of diabetic neuropathy (DPN). METHODS: Total 530 patients with type 2 diabetes were enrolled retrospectively. We rated severity of DPN from 1 (normal) to 4 (severe) based on electrophysiologic findings. We collected the data concerning vascular factors (including brachial-ankle pulse wave velocity [PWV], ankle brachial index, ultrasound of carotid artery, lipid profile from the blood test, and microalbuminuria [MU] within 24 hours urine), and metabolic factors of diabetes (such as glycated hemoglobin [HbA1c]). We analyzed the differences among the four subgroups using χ(2) test and ANOVA, and ordinal logistic regression analysis was performed to investigate the relationship between significant variables and severity of DPN. RESULTS: The severity of DPN was significantly associated with duration of diabetes, HbA1c, existence of diabetic retinopathy and nephropathy, PWV, presence of plaque, low density lipoprotein-cholesterol and MU (p<0.05). Among these variables, HbA1c and presence of plaque were more significantly related with severity of DPN in logistic regression analysis (p<0.001), and presence of plaque showed the highest odds ratio (OR=2.52). CONCLUSION: Our results suggest that markers for vascular wall properties, such as PWV and presence of plaque, are significantly associated with the severity of DPN. The presence of plaque was more strongly associated with the severity of DPN than other variables.

Analysis of the Correlation Among Age, Disc Morphology, Positive Discography and Prognosis in Patients With Chronic Low Back Pain.

OBJECTIVE: To investigate the correlation among age, disc morphology, positive discography, and prognosis in patients with chronic low back pain. METHODS: A total of 183 intervertebral discs in 72 patients with chronic low back pain were studied. Discography was performed using a pressure-controlled manometric technique. The pain reaction during discography at each level was recorded as follows: no pain, dissimilar pain, similar pain, or concordant pain. Discs with similar or concordant pain were classified as positive. All the examined discs were assessed morphologically using axial computed tomography imaging. The grade of general degeneration and annular disruption of the discs were assessed according to the Dallas discogram description (DDD). Intradiscal injection of steroid was tried for patients with symptomatic disc identified during provocative discography and who did not consent to surgical operation. RESULTS: There was a higher correlation between general degeneration and age, as compared with annular disruption and age. Higher general degeneration and annular disruption grades had higher positive rates of discography. However, annular disruption alone was independently associated with positive discography. Age and grade of general degeneration did not affect the prognosis. CONCLUSION: The grade of general degeneration was associated with age, but it was not correlated with positive discography and prognosis. In addition, high grade of annular disruption correlated with positive discography.

The lack of relationship between intracranial pressure and cerebral ventricle indices based on brain computed tomography in patients undergoing ventriculoperitoneal shunt.

BACKGROUND: In this study we investigated whether cerebral ventricle indices based on brain computed tomography (CT) scans are reliable for predicting intracranial pressure (ICP) in hydrocephalic patients. METHODS: Electronic medical records of 221 patients undergoing ventriculoperitoneal shunt due to hydrocephalus were retrospectively reviewed. Cerebral ventricle indices including Evans' index, third ventricle index, cella media index, and ventricular score were calculated from transverse diameters measured at various levels on preoperative brain CT scans. ICP was considered as CSF opening pressure. Patients were categorized into three groups: communicating hydrocephalus, non-communicating hydrocephalus, and normal pressure hydrocephalus (NPH). The non-communicating hydrocephalus group was further divided according to the obstruction site; aqueduct, fourth ventricle outlet, third ventricle, and the foramen of Monro. The primary endpoint was the extent of the correlation between cerebral ventricle indices and ICP in each hydrocephalus group. RESULTS: No cerebral ventricle index correlated with ICP in patients with communicating hydrocephalus (n = 113) and NPH (n = 62). In the non-communicating hydrocephalus group (n = 46), only the third ventricle index revealed moderate negative correlation with ICP (r = -0.395, p < 0.01). In subgroup analyses, the third ventricle index showed a strong negative relationship with ICP only in patients with the third ventricle obstruction (r = -0.779, p < 0.05). CONCLUSIONS: In this study we showed that although an inverse correlation existed between ICP and the third ventricle index only in patients with non-communicating hydrocephalus due to obstruction of the third ventricle, cerebral ventricle indices based on brain CT scan were non-reliable predictors of ICP in hydrocephalic patients.

An enzymatically fortified ginseng extract inhibits proliferation and induces apoptosis of KATO3 human gastric cancer cells via modulation of Bax, mTOR, PKB and IκBα.

Accumulative evidence suggests ginseng extract and/or its major components, ginsenosides and compound K, a metabolized ginseng saponin, have anti-cancer effects. In the present study, the effects of a ginseng butanolic extract (GBX) and an enzymatically fortified ginseng extract (FGX), with enriched ginsenosides and compound K, on the growth of KATO3 human gastric cancer cells were investigated using a cell viability assay. While treatment with GBX at 31.25-125 mg/ml for 24 h did not affect the proliferation of KATO3 cells, FGX under the same conditions inhibited cell proliferation in a concentration-dependent manner. Furthermore, Annexin V/PI-staining and flow cytometric analysis demonstrated that the population of apoptotic KATO3 cells was increased following treatment with FGX, which was greater than in the GBX-treated cells, suggesting that FGX had a stronger apoptotic effect than GBX. To investigate the underlying mechanism of the cytostatic and cytotoxic effects of the ginseng extracts, apoptosis-associated proteins were assessed using western blot analysis. The data revealed higher expression levels of B-cell lymphoma 2-associated X protein (Bax), lower expression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α (IκBα) and reduced phosphorylation of mammalian target of rapamycin (mTOR) and protein kinase B (PKB) in the FGX-treated KATO3 cells than in the GBX-treated cells. Collectively, these results demonstrated for the first time, to the best of our knowledge, that FGX had stronger anti-proliferative and pro-apoptotic effects on KATO3 cells than GBX. The anti-proliferative and/or pro-apoptotic effects of FGX appeared to be mediated via the upregulation of Bax, IκBα proteolysis (activation of nuclear factor-κB) and the blocking of mTOR and PKB signals.

Inhibition of CYP4A reduces hepatic endoplasmic reticulum stress and features of diabetes in mice.

BACKGROUND & AIMS: Endoplasmic reticulum (ER) stress is implicated in the development of type 2 diabetes mellitus. ER stress activates the unfolded protein response pathway, which contributes to apoptosis and insulin resistance. We investigated the roles of cytochrome P450 4A (CYP4A) in the regulation of hepatic ER stress, insulin resistance, and the development of diabetes in mice. METHODS: We used mass spectrometry to compare levels of CYP450 proteins in livers from C57BL/6J and C57BL/KsJ-db/db (db/db) mice; findings were confirmed by immunoblot and real-time PCR analyses. To create a model of diet-induced diabetes, C57BL/6J mice were placed on high-fat diets. Mice were given intraperitoneal injections of an inhibitor (HET0016) or an inducer (clofibrate) of CYP4A, or tail injections of small hairpin RNAs against CYP4A messenger RNA; liver tissues were collected and analyzed for ER stress, insulin resistance, and apoptosis. The effect of HET0016 and CYP4A knockdown also were analyzed in HepG2 cells. RESULTS: Levels of the CYP4A isoforms were highly up-regulated in livers of db/db mice compared with C57BL/6J mice. Inhibition of CYP4A in db/db and mice on high-fat diets reduced features of diabetes such as insulin hypersecretion, hepatic steatosis, and increased glucose tolerance. CYP4A inhibition reduced levels of ER stress, insulin resistance, and apoptosis in the livers of diabetic mice; it also restored hepatic functions. Inversely, induction of CYP4A accelerated ER stress, insulin resistance, and apoptosis in livers of db/db mice. CONCLUSIONS: CYP4A proteins are up-regulated in livers of mice with genetically induced and diet-induced diabetes. Inhibition of CYP4A in mice reduces hepatic ER stress, apoptosis, insulin resistance, and steatosis. Strategies to reduce levels or activity of CYP4A proteins in liver might be developed for treatment of patients with type 2 diabetes.

Lactobacillus casei extract induces apoptosis in gastric cancer by inhibiting NF-κB and mTOR-mediated signaling.

Lactobacillus casei extract (LBX) has been reported to prevent gastric cancer, but the underlying mechanism remains unclear. The proliferation and cell death of gastric cancer KATO3 cells were examined after treatment with LBX for various times and at various doses. LBX inhibited the growth of gastric cancer cells and induced apoptosis by inactivating NF-κB promoter activity. Apoptosis induced by LBX, however, is not directly associated with the intrinsic mitochondrial pathway. Immunoblot analysis revealed that LBX decreased the expressions of NF-κB and IκB. The reduced NF-κB levels led to the decreased phosphorylation of mTOR signaling components, such as PI3K, Akt, and (p70)S6 kinase. These results showed for the first time that LBX induced apoptosis in gastric cancer cells by inhibiting NF-κB and mTOR-mediated signaling.

Mountain ginseng extract exhibits anti-lung cancer activity by inhibiting the nuclear translocation of NF-κB.

Administration of mountain ginseng (MG) extract can restore advanced cancer to a normal state. To elucidate the mechanism by which MG extract prevents the progression of lung cancer, the processes of proliferation and death of lung cancer cells (A549) were examined after treatment with MG extract. Butanol-extracted MG (BX-MG) showed a high inhibitory effect (IC(50) = 2 mg/ml) by attenuating proliferation and inducing apoptosis in lung cancer cells. By HPLC-UV analysis of BX-MG, ginsenosides, Rb1 was identified as the most abundant ginsenoside, followed by Rg1, Re, Rc and Rb2. BX-MG induced caspase-3 dependent apoptosis by inhibiting NF-κB. In addition, BX-MG activated p53 and p21, resulting in the attenuated proliferation of A549 cells. Reduced activity of the NF-κB promoter and increased activity of the p53 promoter indicate that BX-MG regulates apoptosis at the level of transcription in lung cancer cells. Furthermore, BX-MG blocked the nuclear translocation of RelA and the associated reduction in surviving. These results suggest that BX-MG inhibits lung cancer cell growth by activating tumor suppressors and inhibiting nuclear translocation of NF-κB.