Initial phase establishment of an in vitro method for developmental neurotoxicity test using Ki-67 in human neural progenitor cells.

Building a precise alternative neurotoxicological test is of great importance to respond to societal and ethical requirements. In this study, a new developmental neurotoxicity test (DNT) was established with the human neural progenitor cell line. ReNcell CX cells were exposed to neurotoxic chemicals (aphidicolin, hydroxyurea, cytosine arabinoside, 5-fluorouracil, and ochratoxin A) or non-neurotoxic chemicals (sodium gluconate, sodium bicarbonate, penicillin G, and saccharin). Propidium iodide (PI) was used to evaluate cell viability. BrdU and Ki-76 were employed to determine cell proliferation. Based on the cell viability and proliferation, mathematical models were built by linear discriminant analysis. Furthermore, the neurotoxic-considered chemicals inhibited cell cycle progression at the protein level, supporting the biomolecular rationale for the predictive model. Overall, these results show that the new test method can be used to determine the potential developmental neurotoxicants or new drug candidates.

Efficacy of detergent-based cleaning and wiping against SARS-CoV-2 on high-touch surfaces.

Efficacy of cleaning methods against SARS-CoV-2 suspended in either 5% soil load (SARS-soil) or simulated saliva (SARS-SS) was evaluated immediately (hydrated virus, T0) or 2 hours post-contamination (dried virus, T2). Hard water dampened wiping (DW) of surfaces, resulted in 1.77-3.91 log reduction (T0) or 0.93-2.41 log reduction (T2). Incorporating surface pre-wetting by spraying with a detergent solution (D + DW) or hard water (W + DW) just prior to dampened wiping did not unilaterally increase efficacy against infectious SARS-CoV-2, however, the effect was nuanced with respect to surface, viral matrix, and time. Cleaning efficacy on porous surfaces (seat fabric, SF) was low. W + DW on stainless steel (SS) was as effective as D + DW for all conditions except SARS-soil at T2 on SS. DW was the only method that consistently resulted in > 3-log reduction of hydrated (T0) SARS-CoV-2 on SS and ABS plastic. These results suggest that wiping with a hard water dampened wipe can reduce infectious virus on hard non-porous surfaces. Pre-wetting surfaces with surfactants did not significantly increase efficacy for the conditions tested. Surface material, presence or absence of pre-wetting, and time post-contamination affect efficacy of cleaning methods.

Evaluation of surface disinfection methods to inactivate the beta coronavirus Murine Hepatitis Virus.

The list of EPA-approved disinfectants for coronavirus features many products for use on hard, non-porous materials. There are significantly fewer products registered for use on porous materials. Further, many common, high-touch surfaces fall in between non-porous materials such as glass and porous materials such as soft fabrics. The objective of this study was to assess the efficacy of selected commercially available disinfectant products against coronaviruses on common, high-touch surfaces. Four disinfectants (Clorox Total 360, Bleach solution, Vital Oxide, and Peroxide Multi-Surface Cleaner) were evaluated against Murine Hepatitis Virus A59 (MHV) as a surrogate coronavirus for SARS-CoV-2. MHV in cell culture medium was inoculated onto four materials: stainless steel, latex-painted drywall tape, Styrene Butadiene rubber (rubber), and bus seat fabric. Immediately (T0) or 2-hr (T2) post-inoculation, disinfectants were applied by trigger-pull or electrostatic sprayer and either held for recommended contact times (Spray only) or immediately wiped (Spray and Wipe). Recovered infectious MHV was quantified by median tissue culture infectious dose assay. Bleach solution, Clorox Total 360, and Vital Oxide were all effective (>3-log10 reduction or complete kill of infectious virus) with both the Spray Only and Spray and Wipe methods on stainless steel, rubber, and painted drywall tape when used at recommended contact times at both T0 and T2 hr. Multi-Surface Cleaner unexpectedly showed limited efficacy against MHV on stainless steel within the recommended contact time; however, it showed increased (2.3 times greater efficacy) when used in the Spray and Wipe method compared to Spray Only. The only products to achieve a 3-log10 reduction on fabric were Vital Oxide and Clorox Total 360; however, the efficacy of Vital Oxide against MHV on fabric was reduced to below 3-log10 when applied by an electrostatic sprayer compared to a trigger-pull sprayer. This study highlights the importance of considering the material, product, and application method when developing a disinfection strategy for coronaviruses on high-touch surfaces.

Coagulopathy after snake envenomation in South Korea.

OBJECTIVE: This retrospective study investigated the nature and severity of venom-induced consumption coagulopathy (VICC) and determined the clotting factors involved in VICC in patients after envenomation by South Korea's snakes. Additionally, we studied the effectiveness of antivenom for the treatment of VICC after envenomation. METHODS: Included patients were divided into three groups according to the severity of VICC (no VICC, partial VICC, and complete VICC). Data, including changes in coagulation parameters during hospitalization and clotting factors at presentation, were collected and analyzed. RESULTS: One hundred nineteen patients who presented at our emergency department within 3 h after snake envenomation were included. VICC developed in 34 patients (27 patients with partial VICC and 7 patients with complete VICC). Two of 34 patients with VICC required blood transfusions. Five patients with complete VICC had an undetectable fibrinogen concentration at presentation. Three patients with complete VICC had an unmeasurable INR and aPTT within 24 h. The median times of the most extreme values were 10 h for INR, 12 h for aPTT, and 16 h for fibrinogen after presentation in the VICC group. The D-dimer concentration peaked at a median of 63.5 h after presentation. The activities of factors II and X were significantly reduced in the complete VICC group (factor II: 88 (84-99.3)% in the non-VICC group vs. 69 (49.5-83.5)% in the complete VICC group; factor X:94 (83-102) in the non-VICC group vs. 70 (66.5-79.8)% in the complete VICC group), while there was no difference in factor V activity at presentation. The time from bite to first antivenom administration did not correlate with the time course and most extreme concentrations for fibrinogen and D-dimer within the VICC groups. DISCUSSION AND CONCLUSION: VICC occurs in approximately one-quarter of snakebite patients in South Korea; however, VICC itself does not appear to lead to clinical deterioration. Fibrinogen is an early diagnostic maker for complete VICC. Clotting factors II and X are involved in VICC. Future investigations should explore the mechanism of VICC from Korean snakebites and the effect of antivenom on VICC.

The effect of myocardial injury on the clinical course of snake envenomation in South Korea.

CONTENT: This study investigated the incidence, progression and clinical course of myocardial injury-related snake envenomation in South Korea. In addition, this study evaluated whether antivenom guidelines are appropriate to control envenomation in patients with myocardial injury. METHODS: The study included 198 patients who received antivenom after a snakebite, and they were divided into two groups according to evidence of myocardial injury (defined as elevated troponin I or ischemic change on electrocardiogram) at presentation. Data including serial troponin I, echocardiogram/coronary angiogram findings, the clinical course, and treatment were collected and analyzed. RESULTS: The incidence of myocardial injury at presentation was 15.2%. The troponin I level was 0.11 (0.07-0.56) ng/ml at presentation and tended to decrease over 24 h. Echocardiograms revealed neither regional wall motion abnormalities nor left ventricular dysfunction in 15 of 17 patients, while two patients showed signs of coronary artery stenosis on echocardiograms and coronary angiograms. However, compared with patients without myocardial injury, patients with myocardial injury had a higher frequency of systemic envenomation complications, including bleeding, respiratory failure, hypotension, acute kidney injury, thrombocytopenia and venom-induced consumption coagulopathy (VICC). The patients with myocardial injury at presentation needed significantly more frequent and larger doses of antivenom than indicated by the initial severity of envenomation. Multivariate analysis showed that myocardial injury was associated with the need for additional antivenom administration after initial administration. DISCUSSION AND CONCLUSION: Myocardial injury is not uncommon after snake envenomation in Korea. Although myocardial injury itself seems to be benign, the clinical course of patients with myocardial injury is complicated, and myocardial injury is associated with the need for additional antivenom administration. The optimal use of antivenom to control envenomation in patents with myocardial injury after snake envenomation in South Korea should be established.

The concordance rate of non-chromosomal congenital malformations in twins based on zygosity: a retrospective cohort study.

OBJECTIVE: To examine the concordance rate of non-chromosomal congenital malformations in twin pairs based on zygosity. DESIGN: Retrospective cohort study. SETTING: A tertiary hospital in Korea. POPULATION: Twin pairs born at Seoul National University Hospital between 2001 and 2019. METHODS: Congenital malformations were diagnosed by postnatal workups of neonates or autopsy in cases of stillborn infants. Zygosity was confirmed by sex, chorionicity and DNA analysis. MAIN OUTCOME MEASURES: Concordance rate of congenital malformations in twin pairs based on zygosity. RESULTS: In total, 3386 twin pairs were included. The risk of a congenital malformation in the index twin increased significantly if the co-twin had the congenital malformation, and the concordance rate was higher in monozygotic (MZ) than in dizygotic (DZ) twins (37.04 versus 16.77, P < 0.001). An increased risk of a congenital malformation in the presence of the same congenital malformation in the co-twin was observed only for malformations of the nervous system, eye/ear/face/neck, circulatory system, cleft lip/palate, genital organs, urinary system and musculoskeletal system. Significantly higher concordance rates in MZ than in DZ twin pairs were observed only for the nervous system (40.00 versus 0.00, P < 0.001), circulatory system (32.97 versus 19.74, P = 0.021), cleft lip/palate (44.44 versus 0.00, P = 0.017) and urinary system (22.22 versus 0.00, P = 0.004), whereas significant differences were not found for the genital organs or musculoskeletal system. CONCLUSIONS: Monozygotic twins had higher concordance rates than DZ twins only in specific organ systems. It may be speculated that nervous system, circulatory system, cleft lip/palate and urinary system are primarily genetically affected. TWEETABLE ABSTRACT: Monozygotic twins had higher concordance rates than dizygotic twins only in specific organ systems.

Second-phase validation study of an alternative developmental toxicity test using mouse embryonic stem cell-derived embryoid bodies.

The embryoid body test (EBT) is a developmental toxicity test method that measures the size of embryoid bodies (EBs) and the viability of mouse embryonic stem cells (mESCs) and fibroblasts (3T3 cells). The previous pre-validation study confirmed the high accuracy (above 80%) of EBT using 26 coded test chemicals. This second-phase validation study assessed the inter-laboratory reproducibility (5 chemicals in common) and predictive capacity (10 chemicals in each laboratory) test using the coded test chemicals at three laboratories. For the prediction model, the accuracy is increased when more data is accumulated. Therefore, we updated the prediction model and analyzed the results of the second year with the newly created-prediction model. Statistical analysis of the inter-laboratory reproducibility test results indicated that accuracy, sensitivity, and specificity were 87%, 78%, and 100%, respectively. The results of the statistical analysis of the predictive capacity test showed an accuracy of 80%, sensitivity of 78%, and specificity of 81%. In conclusion, the EBT can accurately classify various embryotoxicants within a short period and with relatively little effort. Therefore, EBT can be used as a good way to test developmental toxicity.

Distinctive patterns of pulmonary function change according to baseline lung volume and diffusing capacity.

SETTING: Multicentre retrospective study in South Korea.OBJECTIVE: To longitudinally evaluate changes in lung volume and diffusing capacity for carbon monoxide (DLCO) with forced expiratory volume in 1 sec (FEV1).DESIGN: A total of 155 patients with chronic obstructive pulmonary disease (COPD), whose pulmonary function parameters were measured annually for 5 years, were selected from a prospective cohort in South Korea. A random coefficients model was used to estimate mean annual FEV1, lung volume parameter and DLCO change rates.RESULTS: Patients were classified into four groups based on baseline DLCO and residual volume/total lung capacity (RV/TLC) measurements. The annual FEV1 decline rate was greater in patients with low DLCO than in those with normal DLCO, with the greatest decline occurring in patients with low DLCO and normal RV/TLC. RV and RV/TLC declined in patients with high RV/TLC, whereas these increased in patients with normal RV/TLC. DLCO decreased longitudinally in all four groups, with the greatest decline occurring in patients with normal DLCO and normal RV/TLC.CONCLUSIONS: Different subgroups of patients with COPD exhibited distinctive pulmonary function change patterns. Baseline DLCO and RV/TLC may be used as physiological markers to predict long-term changes in pulmonary function.

Association of plasma fibrinogen concentrations and blood eosinophil counts with clinical phenotypes of COPD.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the plasma fibrinogen level is associated with a decline in lung function and exacerbation of COPD. High blood eosinophil count is also associated with exacerbation of COPD in some studies but not others.OBJECTIVE: To investigate the associations between clinical phenotypes and plasma fibrinogen levels and blood eosinophil counts in patients with COPD.METHODS: Outpatients with COPD, in whom plasma fibrinogen level and blood eosinophil count were measured at least once simultaneously, were analysed retrospectively. Patients were classified into four groups, based on plasma fibrinogen level (threshold, 350 mg/dl) and blood eosinophil percentage (threshold, 2%). Clinical characteristics, comorbidities, laboratory data, COPD severity and exacerbations were compared in the four groups.RESULTS: Of 370 patients with COPD, the group with both high fibrinogen levels and eosinophil counts had more severe airflow limitation, more comorbidities and higher COPD severity indexes than the groups with low plasma fibrinogen. The annual rates of severe (0.29/year) and total (0.42/year) exacerbations were significantly higher in patients with both high fibrinogen and eosinophils than in the other three groups.CONCLUSION: Plasma fibrinogen levels and blood eosinophil counts may predict the clinical phenotype and frequency of exacerbations of COPD.

The impact of hyperthermia after acute carbon monoxide poisoning on neurological sequelae.

This study investigated whether hyperthermia within the first 24 h after presentation was associated with long-term neurological outcomes after acute carbon monoxide (CO) poisoning. This retrospective study included 200 patients with acute severe CO poisoning. Hyperthermia (≥ 37.5°C) developed during the first 24 h after presentation in 55 (27.5%) patients, and poor long-term neurological sequelae assessed at 23 months after acute CO poisoning developed in 19.5% of the patients. The incidence of poor long-term neurological outcomes was significantly higher in the hyperthermia group than in the normothermia group. Patients with poor long-term neurological outcomes had higher maximum temperatures than patients with good outcomes. No significant difference was found in the time of hyperthermia onset within the first day according to the neurological outcomes. Hyperthermia (adjusted odds ratio (aOR) 5.009 (95% confidence interval (CI) 1.556-16.126)) and maximum temperature (aOR 2.581 (95% CI 1.098-6.063)) within the first 24 h after presentation to the emergency department were independently associated with poor long-term neurological outcomes. Body temperature measurements, which are easily and noninvasively recorded at the bedside in any facility, help to predict the risk for poor long-term neurological outcomes. This study carefully emphasizes fastidious control of pyrexia, particularly during the early period after acute CO poisoning.

Identification of chronic obstructive pulmonary disease subgroups in 13 Asian cities.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition that can differ in its clinical manifestation, structural changes and response to treatment. OBJECTIVE: To identify subgroups of COPD with distinct phenotypes, evaluate the distribution of phenotypes in four related regions and calculate the 1-year change in lung function and quality of life according to subgroup. METHODS: Using clinical characteristics, we performed factor analysis and hierarchical cluster analysis in a cohort of 1676 COPD patients from 13 Asian cities. We compared the 1-year change in forced expiratory volume in one second (FEV1), modified Medical Research Council dyspnoea scale score, St George's Respiratory Questionnaire (SGRQ) score and exacerbations according to subgroup derived from cluster analysis. RESULTS: Factor analysis revealed that body mass index, Charlson comorbidity index, SGRQ total score and FEV1 were principal factors. Using these four factors, cluster analysis identified three distinct subgroups with differing disease severity and symptoms. Among the three subgroups, patients in subgroup 2 (severe disease and more symptoms) had the most frequent exacerbations, most rapid FEV1 decline and greatest decline in SGRQ total score. CONCLUSION: Three subgroups with differing severities and symptoms were identified in Asian COPD subjects.

Serum neuron-specific enolase levels at presentation and long-term neurological sequelae after acute charcoal burning-induced carbon monoxide poisoning.

OBJECTIVE: This study aimed to investigate whether clinical parameters and serum neuron-specific enolase (NSE) levels measured at emergency department (ED) presentation help stratify the risk of acute or delayed persistent severe neurological sequelae after acute carbon monoxide (CO) poisoning induced by charcoal burning. METHODS: This retrospective study included 236 patients who suffered from CO poisoning. Demographic information, serum NSE levels measured in the ED, treatment, clinical course, and long-term neurological outcomes were recorded. RESULTS: The median serum NSE level at presentation was 15.5 (10.9-22.7) ng/mL. No differences were observed in the duration of CO exposure; the initial Glasgow Coma Scale (GCS) score; the levels of arterial HCO3-, white blood cells (WBCs), C-reactive protein (CRP) or troponin I; or the frequency of abnormal diffusion-weighted imaging finding at presentation among the groups with different serum NSE levels at presentation. The incidences of acute and delayed persistent neurologic sequelae assessed at 22.3 months after acute charcoal CO poisoning were 5.1% and 8.5%, respectively. No difference in the NSE level was observed between patients stratified according to long-term neurological status. According to the multinomial logistic regression analysis, age, serum CRP levels and the initial GCS score were risk factors for the two types of persistent severe neurological sequelae, whereas troponin I levels were associated only with the acute persistent severe neurological sequelae. However, the adjusted NSE level was not a risk factor for any persistent neurological sequelae. CONCLUSIONS: Serum NSE levels at presentation were not correlated with the risk of acute or delayed persistent neurological sequelae. Further studies with blood sampling at optimal time points and serial measurements should be conducted. Age, initial GCS score, and CRP levels may be risk factors for persistent severe neurological sequelae.

In-hospital outcomes and delayed neurologic sequelae of seizure-related endosulfan poisoning.

PURPOSE: This study investigated the predictive factors for progression from seizure-related endosulfan poisoning to status epilepticus (SE) and refractory SE (RSE). This study also investigated delayed neurologic sequelae in seizure-related endosulfan poisoning. METHODS: This retrospective, observational case series consisted of 73 patients who developed at least one seizure after endosulfan ingestion. RESULTS: The progression rates from seizure-related endosulfan poisoning to SE and from SE-related endosulfan poisoning to RSE were 78.1% and 54.4%, respectively. The SE and RSE fatality rates were 19.2% and 41.9%, respectively. No patients reported the development of delayed neurological sequelae at least six months after discharge. Glasgow coma scale (GCS) score were identified as an independent factor for progression from seizure-related endosulfan poisoning to SE and from SE-related endosulfan poisoning to RSE. Lorazepam administration was independently associated with preventing progression from SE-related endosulfan poisoning to RSE. CONCLUSION: Seizure-related endosulfan poisoning had higher progression rates to SE and RSE and higher fatality rates than other drug-induced seizures. However, delayed neurologic sequelae after discharge were not demonstrated. Due to the high progression rates from seizure-related endosulfan poisoning to SE and RSE and the absence of an established treatment for SE-related endosulfan poisoning, physicians should aggressively treat patients who experience a seizure after endosulfan poisoning and who present with decreased GCS score. Lorazepam should be considered a first-line anti-epileptic drug for controlling seizures in patients with endosulfan poisoning.

Randomized clinical trial of preoperative skin antisepsis with chlorhexidine gluconate or povidone-iodine.

BACKGROUND: Skin antiseptic agents are used to prevent surgical-site infection (SSI); few trials have reported the superiority of any specific agent in clean-contaminated abdominal surgery. This RCT was designed to compare the effectiveness of chlorhexidine gluconate and povidone-iodine. METHODS: Consecutive patients who underwent clean-contaminated upper gastrointestinal or hepatobiliary-pancreatic open surgery between 2011 and 2014 were assigned randomly to either chlorhexidine gluconate or povidone-iodine. The primary endpoint was the occurrence of SSI within 30 days of surgery. Secondary endpoints included causative organisms and risk factors for SSI. RESULTS: A total of 534 patients were randomized; 31 (5·8 per cent) developed an SSI. There was no difference in the overall SSI rate in the chlorhexidine gluconate and povidone-iodine groups: 15 of 267 (5·6 per cent) and 16 of 267 (6·0 per cent) respectively (P = 0·853). The most common causative organism was Enterococcus faecalis. In subgroup analysis, biliary-pancreatic surgery had a higher SSI rate (26 of 127, 20·5 per cent) than upper gastrointestinal (2 of 204, 1·0 per cent) and hepatic (3 of 203, 1·5 per cent) resection. Both age (60 years and over) and type of incision were associated with the risk of SSI. CONCLUSION: No difference was detected between chlorhexidine gluconate and povidone-iodine antiseptics for prevention of SSI. Registration number: NCT01495117 (http://www.clinicaltrials.gov).

Sex Difference in Chronic Obstructive Lung Disease. Does it Matter? A Concise Review.

Chronic obstructive lung disease (COPD) primarily affects men; however, its epidemiology has been changing because more women have become smokers. Recently, investigators found that although women and men were exposed to the same amount of smoke fume, women tended to have more severe disease and higher mortality rate. They also complain of more dyspnoea and may experience more severe exacerbations than men. This led to the question of whether sex has an impact on COPD course and whether women have a higher susceptibility to smoke fumes than men. That may be explained by multiple complex factors highlighting the relationship between sex, epidemiology, method of diagnostics and the clinical course of the disease. In this review, sex differences in epidemiology, clinical presentation, exacerbation, co-morbidities and treatment are covered.

Randomised clinical trial: a phase 1, dose-ranging study of the anti-matrix metalloproteinase-9 monoclonal antibody GS-5745 versus placebo for ulcerative colitis.

BACKGROUND: Matrix metalloproteinase-9 is a proteolytic enzyme whose expression is increased in ulcerative colitis. AIM: To evaluate the safety and efficacy of GS-5745, a fully humanised anti-matrix metalloproteinase-9 monoclonal antibody, in moderately-to-severely active ulcerative colitis. METHODS: We randomised 74 patients with ulcerative colitis to treatment with single or multiple ascending intravenous or subcutaneous doses of GS-5745 or placebo. Multiple-dose cohorts received either IV infusions (0.3, 1.0, 2.5 or 5.0 mg/kg GS-5745 or placebo) every 2 weeks (three total IV infusions) or five weekly SC injections (150 mg GS-5745 or placebo). The primary outcomes were the safety, tolerability and pharmacokinetics of escalating single and multiple doses of GS-5745. Exploratory analyses in the multiple-dose cohorts included clinical response (≥3 points or 30% decrease from baseline in Mayo Clinic score and ≥1 point decrease in the rectal bleeding subscore or a rectal bleeding subscore ≤1) and clinical remission (a complete Mayo Clinic score ≤2 with no subscore >1) at Day 36. Biological effects associated with a clinical response to GS-5745 were explored using histological and molecular approaches. RESULTS: Twenty-three of the 42 patients (55%) receiving multiple doses of GS-5745 had adverse events, compared with 5/8 patients (63%) receiving placebo. GS-5745 showed target-mediated drug disposition, approximately dose-proportional increases in maximum plasma concentration and more than dose-proportional increases in the area under the plasma drug concentration-time curve. Clinical response occurred in 18/42 patients (43%) receiving GS-5745 compared with 1/8 patients (13%) receiving placebo. Clinical remission occurred in 6/42 patients (14%) receiving GS-5745 and 0/8 (0%) receiving placebo. Patients with a clinical response to GS-5745 had reductions in matrix metalloproteinase-9 tissue levels (mean 48.9% decrease from baseline compared with a mean 18.5% increase in nonresponders, P = 0.008) significant improvements in histopathology scores (confirmed with three separate histological disease activity indices), as well as changes in colonic gene expression that were consistent with reduced inflammation. CONCLUSION: This phase 1 trial provides preliminary evidence for the safety and therapeutic potential of GS-5745 in the treatment of ulcerative colitis.

Impact of Intra-Abdominal Adhesion on Living Donor Right Hepatectomy.

The impact of intra-abdominal adhesion (IAA) on living donor right hepatectomy (LDRH) remains to be clarified. The purpose of this study was to compare both the donor and recipient outcomes of right lobe living donor liver transplantation according to IAA detected intraoperatively. LDRH donors were identified through a prospectively maintained database at the authors' institution between March 2008 and February 2014. IAA was graded according to Beck et al (Dis Colon Rectum 2000; 43: 1749-1753). LDRH donors with IAA (group A) were matched 1:3 to those without IAA (group B) based on age, gender, and BMI. Perioperative data, complications by the Clavien classification, and the outcomes with at least 12 months follow-up were compared. Thirty-two (7.6%) of a total of 420 LDRH donors had IAA around the liver. Nineteen donors had previous abdominal surgery. LDRH was successfully completed under upper midline laparotomy in all donors. Compared with group B, group A had a longer operative time (270 vs. 172 min; p < 0.001), a higher wound complication rate (28.1% vs. 4.2%; p = 0.009), and a longer postoperative stay (10 vs. 7 days; p = 0.009). All donors recovered completely to their previous activities. The 1-year graft and recipient survivals of recipients were comparable between two groups. These findings support the feasibility and safety of LDRH in patients with IAA.

Randomised clinical trial: vercirnon, an oral CCR9 antagonist, vs. placebo as induction therapy in active Crohn's disease.

BACKGROUND: Many patients with active Crohn's disease do not adequately respond to therapies, highlighting the need for new treatments. AIMS: To conduct a randomised, double-blind, placebo-controlled phase 3 study to assess the efficacy and safety of vercirnon, an oral inhibitor of CC chemokine receptor-9, for the treatment of patients with moderately-to-severely active Crohn's disease. METHODS: Patients with a Crohn's Disease Activity Index (CDAI) of 220-450, plus evidence of active disease (endoscopically confirmed or elevation of both C-reactive protein and faecal calprotectin), who had failed corticosteroid or immunosuppressant therapy were enrolled. Patients were equally randomised to receive placebo, vercirnon 500 mg once daily or vercirnon 500 mg twice daily. The primary endpoint was clinical response, defined as a 100-point decrease in CDAI from baseline to week 12. RESULTS: Six hundred and eight patients were randomised. Patient characteristics and baseline demographics were similar among the groups. The proportions of patients achieving a clinical response were 25.1%, 27.6% and 27.2% for placebo, once daily and twice daily respectively; treatment differences were not significant (2.5%; 95% confidence interval, CI -6.1% to 11.0%, P = 0.546 for once daily vs. placebo, and 2.1%; 95% CI -6.5% to 10.7%, P = 0.648 for twice daily vs. placebo). Adverse events were reported in 69.8%, 73.3% and 78.1% with serious adverse events in 8.9%, 5.9%, and 6.0% of patients in the placebo, once-daily and twice-daily groups, respectively. CONCLUSIONS: We did not demonstrate efficacy of vercirnon as an induction therapy in patients with moderately-to-severely active Crohn's disease; its effect in maintenance therapy was not addressed.

Outcomes of Early Conversion From Prograf to Generic Tacrolimus in Adult Living Donor Liver Transplant Recipients.

The aim of this study was to evaluate the safety and efficacy of early conversion from the reference tacrolimus (Prograf; Astellas Pharma, Tokyo, Japan) to the generic tacrolimus (Tacrobell®:Chong Kun Dang Pharma, Seoul, Korea) in a cohort of adult living donor liver transplant (LDLT) recipients at a single institution. Between March 2010 and May 2012, a 1:1 dose conversion was performed 2 to 4 weeks after LDLT with dose adjustments targeted to achieve trough concentrations within the therapeutic range. Tacrolimus doses and trough levels, laboratory parameters, and adverse events were assessed. A total of 149 patients were enrolled. The median transplant duration was 22 days (range; 15-28 days). During a median follow-up of 17.3 months after conversion, there were 3 episodes of acute rejection, all of which responded to high-dose steroids. No adverse events were serious enough to stop the drug. In comparison with the control group maintained on Prograf, there were no significant differences in outcomes. In conclusion, early conversion from the reference to generic tacrolimus is safe and effective in stable adult LDLT patients.