Comparison of two different preload targets of stroke volume variation during kidney transplantation: a randomised controlled trial.

INTRODUCTION: Maintaining adequate preload during kidney transplantation (KT) is important for graft function. We evaluated whether a high or low normal target for a dynamic preload index of stroke volume variation (SVV) would impact graft function during living donor KT. METHODS: We compared haemodynamic management algorithms using two different targets of SVV: SVV6% group (n = 30) versus SVV12% group (n = 30). Crystalloids were administered to achieve SVV less than the assigned target. Neutrophil gelatinase-associated lipocalin (NGAL) level at the end of surgery was compared. We also compared the incidence of delayed graft function (DGF), daily serum creatinine level and glomerular filtration rate (GFR) until 2 weeks postoperatively. RESULTS: The total amount of crystalloids administered was significantly different between the SVV6% and SVV12% groups (median [interquartile range] 2,250 [1,700-3,600] vs. 1,350 [1,050-1,900], P < 0.001). There was no significant difference in NGAL level at the end of the operation between the SVV6% and SVV12% groups (395 [234-560] vs. 518 [346-654], P = 0.115). The incidence of DGF was not significantly different, and there was no significant difference in the postoperative serum creatinine levels or GFR between the groups. CONCLUSIONS: Our randomised trial demonstrated that an SVV target of either 6% or 12% could be adequate as a preload management target for postoperative graft function during living donor KT. However, given the low incidence of DGF in living donor KT and type II error, our study should be interpreted carefully and further studies for deceased donor KT are required.

Feasibility of Sarcopenia Diagnosis Using Stimulated Muscle Contraction Signal in Hemiplegic Stroke Patients.

Sarcopenia, a condition characterized by muscle weakness and mass loss, poses significant risks of accidents and complications. Traditional diagnostic methods often rely on physical function measurements like handgrip strength which can be challenging for affected patients, including those with stroke. To address these challenges, we propose a novel sarcopenia diagnosis model utilizing stimulated muscle contraction signals captured via wearable devices. Our approach achieved impressive results, with an accuracy of 93% and 100% in sarcopenia classification for male and female stroke patients, respectively. These findings underscore the significance of our method in diagnosing sarcopenia among stroke patients, offering a non-invasive and accessible solution.

The integrity of thalamo-dorsolateral prefrontal cortex tract: a key factor in residual consciousness in disorders of consciousness patients.

Background: The mesocircuit model describes a complex network that includes the prefrontal cortical-striatopallidal-thalamo-cortical loop systems and is involved in the mechanism underlying consciousness in patients with disorders of consciousness (DoC). Inhibitory signals to the thalamus become hyperactive in DoC patients, leading to a loss of consciousness. Reactivating this mesocircuit system is important for recovering consciousness in these patients. We investigated how the residual integrity of the thalamo-dorsolateral prefrontal cortex tract (TDLPFCT) influences consciousness in patients with DoC. Methods: This retrospective case-control study included three groups: prolonged DoC (n = 20), stroke without DoC (n = 20), and healthy controls (n = 20). Diffusion tensor imaging (DTI) was performed at least 4 weeks after the onset. Thalamo-DLPFC tracts were reconstructed using diffusion tensor tractography, and fractional anisotropy (FA) and tract volume (TV) were measured for each hemisphere. Consciousness was assessed using the revised coma recovery scale (CRS-R) within a week of brain imaging. Results: Significant differences in DLPFCT TV were observed across all three groups, in both affected and less-affected lobes, with the DoC group showing the greatest reduction. A significant correlation was found between the TV of the less-affected TDLPFCT and CRS-R score. Conclusion: The integrity of the TDLPFCT, particularly in the less affected hemisphere, is associated with consciousness levels in patients with prolonged DoC. This finding suggests its potential importance in assessing prognosis and further developing therapeutic strategies for patients with DoC.

Association between intraoperative tidal volume and postoperative acute kidney injury in non-cardiac surgical patients using a propensity score-weighted analysis.

Acute kidney injury (AKI) is related to adverse clinical outcomes. Therefore, identifying patients at increased risk of postoperative AKI and proactively providing appropriate care is crucial. However, only a limited number of modifiable risk factors have been recognized to mitigate AKI risk. We retrospectively analyzed adult patients who underwent endotracheal intubation and mechanical ventilation of more than 2 h during non-cardiac surgery at Seoul National University Hospital from January 2011 to November 2022. Patients were grouped into low- or high-tidal volume groups based on their intraoperative tidal volume relative to their predicted body weight (PBW) of 8 ml/kg. The association between intraoperative tidal volume and postoperative AKI was evaluated using inverse probability of treatment weighting (IPTW), adjusting for various preoperative confounders. Among the 37,726 patients included, the incidence of postoperative AKI was 4.1%. The odds of postoperative AKI risk were significantly higher in the high-tidal volume group than in the low-tidal volume group before and after IPTW (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.08-1.32, P = 0.001 and OR: 1.10, 95% CI 1.02-1.19, P = 0.010, respectively). In the multivariable logistic regression analysis after IPTW, a high tidal volume was independently associated with an increased risk of postoperative AKI (OR: 1.21, 95% CI 1.12-1.30, P < 0.001). In this propensity score-weighted analysis, an intraoperative high tidal volume of more than 8 ml/kg PBW was significantly associated with an increased risk of postoperative AKI after IPTW in non-cardiac surgical patients. Intraoperative tidal volume showed potential as a modifiable risk factor for preventing postoperative AKI.

Isolated Acute Dysphagia as a Probable Rare Presentation of Guillain-Barré Syndrome with Complete Recovery: A Case Report.

Dysphagia is prevalent among the elderly and can lead to serious complications, often manifesting as a clinical symptom of various neurological or muscular pathologies, including Guillain-Barré Syndrome (GBS). GBS is an acute immune-mediated polyradiculoneuropathy, and dysphagia may arise during its course due to cranial nerve involvement. In rare GBS variants, dysphagia may present as the initial or sole clinical manifestation, posing diagnostic challenges. In this study, we present the case of an elderly female patient with dysphagia, eventually diagnosed with an atypical variant of GBS. Initially, the patient required nasogastric tube feeding; however, complete recovery was achieved through immunotherapy. This case underscores the importance of clinicians conducting thorough evaluations of factors influencing the swallowing mechanism and remaining vigilant about identifying uncommon causative factors. Such approaches enable the implementation of effective disease-modifying therapies, potentially leading to the resolution of dysphagic symptoms.

The Important Role of GPX1 and NF-κB Signaling Pathway in Human Gastric Cancer: Implications for Cell Proliferation and Invasion.

BACKGROUND/AIM: Glutathione peroxidases (GPXs) are crucial antioxidant enzymes, counteracting reactive oxygen species (ROS). GPX overexpression promotes proliferation and invasion in cancer cells. Glutathione peroxidase-1 (GPX1), the most abundant isoform, contributes to invasion, migration, cisplatin resistance, and proliferation in various cancers. Nuclear factor-kappa B (NF-[Formula: see text]B) participates in cell proliferation, apoptosis, and tumor progression. The inhibition of NF-[Formula: see text]B expression reduces the malignancy of esophageal squamous cell carcinoma. This study aimed to explore the GPX1 and NF-[Formula: see text]B signaling pathways and their correlation with gastric cancer cell proliferation and invasion. MATERIALS AND METHODS: Cell culture, complementary DNA microarray analysis, western blotting, reverse transcription-polymerase chain reaction, zymography, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, GPX1 knock-down with short hairpin RNA (shRNA), standard two-chamber invasion assay, chromatin immunoprecipitation assay. RESULTS: Hepatocyte growth factor (HGF) up-regulated GPX1 expression in gastric cancer cells. The NF-[Formula: see text]B inhibitor, pyrrolidine dithiocarbamate down-regulated HGF-induced GPX1 protein levels. Furthermore, NF-[Formula: see text]B and urokinase-type plasminogen activators were down-regulated in GPX1-shRNA-treated cells. Treatment with an Akt pathway inhibitor (LY294002) led to the down-regulation of GPX1 and NF-[Formula: see text]B gastric cancer cells. GPX1 knockdown resulted in decreased HGF-mediated in vitro cell proliferation and invasion. The study identified the putative binding site of the GPX1 promoter containing the NF-[Formula: see text]B binding site, confirmed through chromatin immunoprecipitation. CONCLUSION: HGF induced GPX1 expression through the NF-[Formula: see text]B and Akt pathways, suggesting a central role in gastric cell proliferation and invasion. Hence, GPX1 emerges as a potential therapeutic target for gastric cancer.

Cold-shock Domain Protein A (CSDA) Influences Hepatocyte Growth Factor-medicated Cell Proliferation and Metastasis in Gastric Cancer Cells.

BACKGROUND/AIM: A role for cold-shock domain (CSD) proteins in abnormal cell proliferation has been suggested in the literature. The aim of this study was to investigate the effect of hepatocyte growth factor (HGF)-induced up-regulation of CSD protein A (CSDA) expression on vascular endothelial growth factor (VEGF) expression and its role in gastric cancer cell invasion and proliferation. MATERIALS AND METHODS: We assessed effects on two gastric cancer cell lines using reverse transcription-polymerase chain reaction, western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and CSDA knockdown with short hairpin RNA. RESULTS: Hepatocyte growth factor (HGF) elevates CSDA levels in gastric cancer cell lines. To elucidate the mechanism by which HGF prompts CSDA expression and its impact on vascular endothelial growth factor (VEGF), we applied the Mitogen Activated Protein Kinase (MAPK) inhibitor PD098059 and conducted analyses using western blot. Following the administration of PD098059, a reduction in the protein levels of HGF-stimulated VEGF was observed. Additionally, silencing of CSDA resulted in diminished levels of both VEGF and phosphorylated extracellular signal-regulated kinase (ERK). The suppression of CSDA also led to reduced HGF-induced cell proliferation and diminished invasive capabilities in vitro. Furthermore, our research pinpointed a potential activator protein-1 (AP-1) binding site within the VEGF promoter zone, validating its activity via chromatin immunoprecipitation assays. Electrophoretic mobility shift assays further disclosed that HGF-induced CSDA augmentation correlates with an increase in AP-1 binding to VEGF. CONCLUSION: CSDA is crucial for the proliferation of gastric cancer cells, and the inhibition of this protein could impede the advancement of gastric cancer.

Intraoperative Normal Saline Administration and Acute Kidney Injury in Patients Undergoing Liver Transplantation.

BACKGROUND: Normal saline is still used in patients undergoing living donor liver transplantation (LDLT) with normonatremia. We investigated whether the normal saline administered during LDLT is associated with the increased risk of acute kidney injury (AKI) compared with the balanced crystalloids. METHODS: We reviewed 1011 cases undergoing LDLT. The primary exposure variable was normal saline administered intraoperatively compared with the balanced crystalloid. To compare the risk of AKI after adjusting for potential confounders of baseline characteristics and surgical parameters, a propensity score matching analysis was performed. As a sensitivity analysis, ordinal logistic regression analysis was performed for AKI using inverse probability of treatment weighting (IPTW). RESULTS: The incidence of AKI was significantly higher in the saline group (n = 88/174, 50.6%) than in the balanced group (n = 67/174, 38.5%) after matching (P = .010). The incidence of stage 2 or 3 AKI was also significantly higher in the saline group (n = 26/174, 14.9%) than in the balanced group (n = 43/174, 24.7%) after matching (P = .022). The length of hospital stay was significantly longer in the saline group than in the balanced group after matching. Ordinal logistic regression analysis using IPTW showed that the saline group showed a significant association of saline administration with the risk of AKI (odds ratio 1.23, 95% CI 1.05-1.28, P = .013). CONCLUSION: Our propensity score analysis using propensity score matching and IPTW showed that normal saline administration during LDLT is associated with a high risk of postoperative AKI and longer hospital stays. However, our results should be interpreted carefully due to the relatively long period of data collection.

Pulmonary artery catheter monitoring versus arterial waveform-based monitoring during liver transplantation: a retrospective cohort study.

Although pulmonary artery catheter (PAC) has been used during liver transplantation surgery, the usefulness of PAC has rarely been investigated. We evaluated whether the use of PAC is associated with better clinical outcomes compared to arterial waveform-based monitoring after liver transplantation. A total of 1565 cases undergoing liver transplantation were reviewed. We determined whether patients received PAC or not and divided our cohort into the PAC with hemodynamic monitoring using PAC and the non-PAC with arterial waveform-based monitoring using FloTrac-Vigileo. Propensity score matching was performed. Acute kidney injury (AKI), early allograft dysfunction (EAD) and 1-year all-cause mortality or graft failure were compared in the matched cohorts. Logistic regression analysis was performed in the inverse probability of treatment-weighted (IPTW) cohort for postoperative EAD and AKI, respectively. Five-year overall survival was compared between the two groups. In the matched cohort, there was no significant difference in the incidence of AKI, EAD, length of hospital or ICU stay, and 1-year all-cause mortality between the groups. In the IPTW cohort, the use of PAC was not a significant predictor for AKI or EAD (AKI: odds ratio (95% confidence interval) of 1.20 (0.47-1.56), p = 0.229; EAD: 0.99 (0.38-1.14), p = 0.323). There was no significant difference in the survival between groups after propensity score matching (Log-rank test p = 0.578). In conclusion, posttransplant clinical outcomes were not significantly different between the groups with and without PAC. Anesthetic management without the use of PAC may be possible in low-risk patients during liver transplantation. The risk should be carefully assessed by considering MELD scores, ischemic time, surgical history, previous treatment of underlying liver disease, and degree of portal and pulmonary hypertension.Registration: https://clinicaltrials.gov/ct2/show/NCT05457114 (registration date: July 15, 2022).

Effect of driving pressure-guided positive end-expiratory pressure on postoperative pulmonary complications in patients undergoing laparoscopic or robotic surgery: a randomised controlled trial.

BACKGROUND: Individualised positive end-expiratory pressure (PEEP) improves respiratory mechanics. However, whether PEEP reduces postoperative pulmonary complications (PPCs) remains unclear. We investigated whether driving pressure-guided PEEP reduces PPCs after laparoscopic/robotic abdominal surgery. METHODS: This single-centre, randomised controlled trial enrolled patients at risk for PPCs undergoing laparoscopic or robotic lower abdominal surgery. The individualised group received driving pressure-guided PEEP, whereas the comparator group received 5 cm H2O fixed PEEP during surgery. Both groups received a tidal volume of 8 ml kg-1 ideal body weight. The primary outcome analysed per protocol was a composite of pulmonary complications (defined by pre-specified clinical and radiological criteria) within 7 postoperative days after surgery. RESULTS: Some 384 patients (median age: 67 yr [inter-quartile range: 61-73]; 66 [18%] female) were randomised. Mean (standard deviation) PEEP in patients randomised to individualised PEEP (n=178) was 13.6 cm H2O (2.1). Individualised PEEP resulted in lower mean driving pressures (14.7 cm H2O [2.6]), compared with 185 patients randomised to standard PEEP (18.4 cm H2O [3.2]; mean difference: -3.7 cm H2O [95% confidence interval (CI): -4.3 to -3.1 cm H2O]; P<0.001). There was no difference in the incidence of pulmonary complications between individualised (25/178 [14.0%]) vs standard PEEP (36/185 [19.5%]; risk ratio [95% CI], 0.72 [0.45-1.15]; P=0.215). Pulmonary complications as a result of desaturation were less frequent in patients randomised to individualised PEEP (8/178 [4.5%], compared with standard PEEP (30/185 [16.2%], risk ratio [95% CI], 0.28 [0.13-0.59]; P=0.001). CONCLUSIONS: Driving pressure-guided PEEP did not decrease the incidence of pulmonary complications within 7 days of laparoscopic or robotic lower abdominal surgery, although uncertainty remains given the lower than anticipated event rate for the primary outcome. CLINICAL TRIAL REGISTRATION: KCT0004888 (http://cris.nih.go.kr, registration date: April 6, 2020).

Serum neutrophil gelatinase-associated lipocalin and lactate level during surgery predict acute kidney injury and early allograft dysfunction after liver transplantation.

Early allograft dysfunction (EAD) and acute kidney injury (AKI) are common and clinically important complications after liver transplantation. Serum lactate level at the end of surgery could predict EAD and neutrophil gelatinase-associated lipocalin (NGAL) is known as a biomarker for AKI after liver transplantation. The authors investigated whether the combination of these two laboratory tests could be used as an early predictor of these two complications of EAD and AKI. We reviewed cases undergoing living donor liver transplantation (n = 353). Lactate-adjusted NGAL level, a combination of these two predictors, was calculated as the sum of each value multiplied by the odds ratio for EAD or AKI. We evaluated whether this combined predictor at the end of surgery is significantly associated with both postoperative AKI or EAD. We compared the area under the receiver operating characteristic curve (AUC) between our multivariable regression models with and without NGAL, lactate, or lactate-adjusted NGAL. NGAL, lactate and lactate-adjusted NGAL are significant predictors for EAD and AKI. The regression model for EAD or AKI including lactate-adjusted NGAL showed a greater AUC (for EAD: odds ratio [OR] 0.88, 95% confidence interval [CI] 0.84-0.91; for AKI: OR 0.89, 95% CI 0.85-0.92) compared to the AUC of the models including lactate (for EAD: OR 0.84, 95% CI 0.81-0.88; for AKI: OR 0.79, 95% CI 0.74-0.83) or NGAL alone (for EAD: OR 0.82, 95% CI 0.77-0.86; for AKI: OR 0.84, 95% CI 0.80-0.88) or the model without lactate or NGAL (for EAD: OR 0.64, 95% CI 0.58-0.69, for AKI: OR 0.75, 95% CI 0.70-0.79). In conclusion, lactate-adjusted NGAL level at the end of surgery could be a reliable combined laboratory predictor for postoperative EAD or AKI after liver transplantation with a greater discriminative ability than lactate or NGAL alone.

Transverse abdominis plane block compared with patient-controlled epidural analgesia following abdominal surgery: a meta-analysis and trial sequential analysis.

Thoracic epidural analgesia (TEA) and transversus abdominis plane (TAP) block are used for pain control after abdominal surgery. Although there have been several meta-analyses comparing these two techniques, the conclusion was limited by a small number of studies and heterogeneity among studies. Our meta-analysis used the Medline, EMBASE, and Cochrane central library databases from their inception through September 2022. Randomized controlled trials (RCTs) comparing TEA and TAP block were included. The pre-specified primary outcome was the pain score at rest at 12 h postoperatively. Twenty-two RCTs involving 1975 patients were included. Pooled analyses showed the pain score at rest at 12 h postoperatively was significantly different between groups favoring TEA group (Mean difference [MD] 0.58, 95% confidence interval CI - 0.01, 1.15, P = 0.04, I2 = 94%). TEA group significantly reduced the pain score at 48 h at rest (MD 0.59, 95% CI 0.15, 1.03, P = 0.009, I2 = 86%) and at 48 h at movement (MD 0.53, 95% CI 0.07, 0.99, P = 0.03, I2 = 76%). However, there was no significant difference at other time points. Time to ambulation was shorter in TAP block but the incidence of hypotension at 24 h and 72 h was significantly lower in TAP block compared to TEA. Trial sequential analysis showed that the required information size has not yet been reached. Our meta-analysis demonstrated there was no significant or clinically meaningful difference in the postoperative pain scores between TEA and TAP block group. Given the insufficient information size revealed by TSA, the high risk of bias of our included studies, and the significant heterogeneity of our meta-analysis results, our results should be interpreted carefully but it is not likely that the addition of further studies could prove any clinically meaningful difference in pain score between these two techniques.

Preservation of Cerebellar Afferent Pathway May Be Related to Good Hand Function in Patients with Stroke.

Many chronic stroke patients suffer from worsened hand function, and functional recovery of the hand does not occur well after six months of stroke. Therefore, predicting final hand function after stroke through acute phase imaging would be an important issue in counseling with the patients or their family. Thus, we investigated the remaining white matter integrity in the corticospinal tract (CST) and cortico-ponto-cerebellar tract (CPCT) at the acute stage of stroke and chronic hand function after stroke, and present the cut-off value of fiber number (FN) and fractional anisotropy (FA) of CST and CPCT at the acute stage for predicting final hand function after the recovery period. This retrospective case-control study included 18 stroke patients who were classified into two groups: poor hand function with stroke (n = 11) and good hand function with stroke (n = 7). DTI was done within two months ± 15 days after onset, and the Jebson's Hand Function test was conducted 6-12 months after onset. The investigation of white matter was focused on the values of FN and FA for CST and CPCT, which were measured separately. The normalized (affected/non-affected) FA and FN values in the CPCT in the good hand function group were higher than those in the poor hand function group. The normalized FN and FA values in the CST were not significantly different between the poor hand function group and the good hand function group. The normalized cut-off value that distinguished the good hand function group from the poor hand function group was 0.8889 for FA in the CPCT. The integrity of the CPCT in the acute stage was associated with hand function in the chronic stage after a stroke. Ultimately, the integrity of the CPCT in the early stage after onset can be used to predict chronic hand function. Based on these results, cerebellar afferent fiber measurements may be a useful addition to predict hand function and plan specific rehabilitation strategies in stroke patients.

Intra-host diversity of drug-resistant cytomegalovirus: A case report of cytomegalovirus infection after allogeneic hematopoietic cell transplantation.

Cytomegalovirus (CMV) is a major infectious agent causing severe complications in allogeneic hematopoietic cell transplantation (HCT) recipients, thereby warranting the need for aggressive preemptive or targeted antiviral therapy. However, prolonged or repeated use of antiviral agents, such as ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV), can result in drug-resistant CMV infection, posing challenges to successful outcomes. Here, we report a case of a patient with acute myeloid leukemia and drug-resistant CMV infection who presented with persistent CMV DNAemia, colitis, pneumonia, and encephalitis. An intra-host diversity of UL97 and UL54 mutations were detected through the genotypic resistance testing conducted on two blood samples (D+199 and D+224) and a cerebrospinal fluid (CSF) specimen (D+260) collected from the patient. UL97 L595W/L595F and L595W mutations were detected in the blood and CSF samples, respectively, that conferred GCV resistance. UL54 F412L mutation detected in all three samples conferred GCV/CDV resistance. However, the V787L mutation of UL54, conferring GCV/FOS resistance, was observed only in the D+224 blood sample. Despite combination therapy with FOS and high dose GCV and adjunctive therapy with leflunomide, the patient died from CMV infection and multiple organ failure on D+279. Further data on resistant mutations and intra-host diversity of CMV should be accumulated to elucidate the antiviral resistance and related outcomes.

HGF induces oncoprotein HCCR-1 expression through the Wnt/ß-catenin pathway in gastric cancer.

OBJECTIVE: Human cervical cancer oncogene (HCCR)-1, previously identified in cervical cancer and its cell lines, has been reported to play an important role in tumor progression in several cancers as a suppressor of apoptosis. However, the role of HCCR-1 in the tumorigenesis of stomach cancer has not been identified. This study examined the role of HCCR-1 as a suppressor of apoptosis during tumorigenesis in gastric cancer, along with its possible regulatory pathway. METHODS: We employed several techniques including western blotting, semiquantitative reverse transcription polymerase chain reaction, diphenyltetrazolium bromide assay, chromatin immunoprecipitation assay, fluorescence-activated cell sorting, and HCCR-1 knockdown with short hairpin RNA to elucidate the role of HCCR-1. RESULTS: We observed that hepatocyte growth factor (HGF) upregulated HCCR-1 expression. In addition, the expression levels of ß-catenin, T cell factor-1 (TCF1), and B-cell lymphoma 2 (bcl2) were increased, whereas that of tumor protein 53 (p53) was decreased following HGF treatment. HCCR-1 knockdown in NUGC-3 and MKN-28 cells decreased the expression of TCF1 and phosphorylated ß-catenin and increased the binding activity on the binding site of the HCCR-1 promoter. This identifies the possible involvement of the Wnt/ß-catenin pathway in HGF-induced HCCR-1 regulation. We also confirmed the role of HCCR-1 in HGF-induced anti-apoptotic activity. p53 protein expression was increased, whereas that of bcl2 was decreased with HGF treatment in HCCR-1 knockdown cells, while the apoptotic activity was increased. CONCLUSION: Our study suggests the anti-apoptotic activity of HGF-induced HCCR-1 expression and that HGF may regulate HCCR-1 via TCF1/ß-catenin in stomach cancer.

A prospective, multicenter, open-label study of the clinical efficacy of tapentadol extended-release in the treatment of cancer-related pain and improvement in the quality of life of opioid-naïve or opioid-resistant patients.

PURPOSE: This study aimed to investigate the clinical efficacy of tapentadol extended-release (ER) on pain control and the quality of life (QoL) of patients with moderate to severe chronic cancer pain in clinical practice in Korea. METHODS: In this prospective, open-label, multicenter trial, patients with sustained cancer pain as well as chronic pain, who were or were not using other analgesics were enrolled. Thirteen centers recorded a total of 752 patients during the 6-month observation period, based on the tapentadol ER dose and tolerability, prior and concomitant analgesic treatment, pain intensity, type of pain, adverse effects, and clinical global impression change (CGI-C). Of those 752 patients, 688 were enrolled, and 650 completed the study for efficacy and adverse drug reactions; among them, 349 were cancer patients. RESULTS: Tapentadol ER significantly reduced the mean pain intensity including neuropathic pain during the observation period by 2.9 points (from a mean 7 ± 0.87 to 4.1 ± 2.02). Furthermore, QoL was observed to be significantly improved based on the CGI-C, an objective measure. CONCLUSION: This study showed that tapentadol ER was effective for treating patients with moderate to severe cancer pain and neuropathic pain, and therefore it significantly improved the patients' QoL.

Nodal is a short-range morphogen with activity that spreads through a relay mechanism in human gastruloids.

Morphogens are signaling molecules that convey positional information and dictate cell fates during development. Although ectopic expression in model organisms suggests that morphogen gradients form through diffusion, little is known about how morphogen gradients are created and interpreted during mammalian embryogenesis due to the combined difficulties of measuring endogenous morphogen levels and observing development in utero. Here we take advantage of a human gastruloid model to visualize endogenous Nodal protein in living cells, during specification of germ layers. We show that Nodal is extremely short range so that Nodal protein is limited to the immediate neighborhood of source cells. Nodal activity spreads through a relay mechanism in which Nodal production induces neighboring cells to transcribe Nodal. We further show that the Nodal inhibitor Lefty, while biochemically capable of long-range diffusion, also acts locally to control the timing of Nodal spread and therefore of mesoderm differentiation during patterning. Our study establishes a paradigm for tissue patterning by an activator-inhibitor pair.

14-3-3 Sigma Protein Contributes to Hepatocyte Growth Factor-mediated Cell Proliferation and Invasion via Matrix Metalloproteinase-1 Regulation in Human Gastric Cancer.

BACKGROUND/AIM: The 14-3-3 protein family has a variety of functions in cellular responses in different organisms, including cell-cycle regulation, apoptosis, and malignant transformation. 14-3-3 Sigma protein (14-3-3σ) induces G2 arrest, which enables repair of damaged DNA. The purpose of this study was to identify the role of 14-3-3σ up-regulation by hepatocyte growth factor (HGF) in cancer cell proliferation and invasion in gastric cancer. MATERIALS AND METHODS: In this study, cell culture, western blotting, real-time polymerase chain reaction, zymography, 14-3-3σ knock-down using short hairpin RNA (shRNA), electrophoresis mobility-shift assay, chromatin immunoprecipitation assay and standard two-chamber invasion assay were applied. RESULTS: Firstly, we confirmed that the expression of 14-3-3σ in gastric cancer cells was up-regulated by HGF. To identify how HGF-induced 14-3-3σ expression affects matrix metalloproteinase-1 (MMP1) expression, the cells were treated with the mitogen-activated protein kinase kinase inhibitor PD098059 and analyzed using western blotting. The HGF-mediated expression of MMP1 protein decreased in the presence of PD098059. The role of 14-3-3σ in MMP1 expression was determined through 14-3-3σ knockdown using shRNA. 14-3-3σ-shRNA cells showed reduced levels of MMP1, phosphorylated extracellular signal-regulated kinase, and pp38. HGF-mediated cell proliferation and in vitro invasion were reduced in 14-3-3σ knockdown cells. Serum 14-3-3σ levels were also significantly reduced following gastrectomy in patients with stage II or stage III gastric cancer (p<0.05). CONCLUSION: These results suggest that 14-3-3σ plays an important role in cell proliferation and metastasis in gastric cancer, and 14-3-3σ may be a novel target for detection and prevention of progression of gastric cancer. In addition, the serum 14-3-3σ level is associated with treatment status in patients with locally advanced gastric cancer.

Hemoptysis in Quadriplegia with Atrial Fibrillation Who Was Taking Edoxaban: a Case Report.

The direct-acting oral anticoagulants (DOACs) would be the standard treatment for the prevention of stroke and thromboembolism in nonvalvular atrial fibrillation patients. The adverse effects of greatest concern are bleeding especially major bleeding. We present a case of a patient with a history of nonvalvular atrial fibrillation and pacemaker, who developed severe anemia after massive hemoptysis while taking DOAC; however, he has continued taking DOAC. Through this case, we have summarized the current management of major bleeding associated with anticoagulation and discuss the optimal regimen for restarting of anticoagulation therapy.