Diagnosis of osteochondral lesions of the talus on Dual-layer spectral detector CT arthrography: clinical feasibility of virtual noncontrast images.

AIM: To compare the image quality of virtual noncontrast (VNC) and true noncontrast (TNC) CT images and to evaluate the clinical feasibility of VNC CT images for assessing osteochondral lesions of the talus (OLTs). MATERIALS AND METHODS: Forty-five OLT patients who underwent ankle CT arthrography (CTA) using dual-layer spectral detector CT were enrolled. Reconstruction of VNC and three-dimensional volume rendering images was performed. Afterward, image noise, the signal-to-noise ratio (SNR), and the contrast-to-noise ratio (CNR) were measured. For the subjective evaluation, two board-certified musculoskeletal radiologists [R2-1] assessed spatial resolution, overall image quality, and lesion conspicuity. The accuracy rate for OLT grading was determined in 23 patients who underwent arthroscopic surgery. RESULTS: While VNC images showed significantly less noise than TNC images, TNC images showed better SNRs and CNRs (p<.01). In the subjective analysis, TNC images showed better overall image quality (p<.001). For the 3D volume rendering images, VNC images scored significantly higher for lesion conspicuity (p<.001). The accuracy rates of CTA and CTA with VNC images for OLT grading were 79.2% and 83.3%, respectively. Regarding confidence level, when CTA and VNC images were evaluated together, the confidence level was significantly higher than that when only CTA images were evaluated (p<.001). CONCLUSION: VNC imaging can provide better confidence level of OLT grading and evaluation of the integrity of the subchondral bone plate when combined with conventional CTA without additional radiation dose to the patient. In addition, VNC images-based 3D volume rendering reconstruction would be helpful for preoperative planning in OLT patients.

Metformin activates AMPK and mTOR to Inhibit RANKL-stimulated osteoclast formation.

OBJECTIVE: Metformin is a medication used to treat type 2 diabetes by inhibiting hepatic glucose production through adenosine monophosphate-activated protein kinase (AMPK) activation. Autophagy is closely related to the homeostasis and stress mechanisms of the body. In recent years, much research has arisen on therapeutic methods utilizing autophagy mechanisms to treat diagnoses such as metabolic diseases, tumors, and Alzheimer's disease. This study thus aimed to investigate the effects of metformin treatment on the differentiation of osteoclasts and changes in AMPK mechanisms, which play an important role in regulating energy homeostasis, and mTOR, a highly conserved kinase that regulates autophagy. MATERIALS AND METHODS: Experimentation, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, tartrate-resistant acid phosphate (TRAP) staining, pit formation assay, immunofluorescence, western blotting, and real-time polymerase chain reaction (PCR) was performed to investigate the effects of metformin on osteoclast differentiation. Additionally, to investigate its association with AMPK and pathways, the AMPK inhibitor compound C and mammalian targets of rapamycin (mTOR) activator leucine were used to examine the expression of osteoclast- or autophagy-related proteins, genes, and TRAP-positive cells. RESULTS: Metformin showed no cytotoxic effects on mouse osteoblastic cell lines (MC3T3-E1) and murine macrophage cell lines (RAW264.7) but did inhibit osteoclast differentiation. Furthermore, metformin was found to inhibit osteoclast differentiation through AMPK activation and mTOR inhibition. In turn, AMPK inhibition using compound C promoted osteoclast differentiation, and mTOR activation using leucine inhibited autophagy and osteoclast differentiation. CONCLUSIONS: Metformin activates the AMPK pathway while functioning as an activator of mTOR, thereby leading to the inhibition of autophagy and osteoclast differentiation.

National prevalence and socioeconomic factors associated with the acceptance of COVID-19 vaccines in South Korea: a large-scale representative study in 2021.

OBJECTIVE: Among the global efforts toward preventing the COVID-19 pandemic, vaccines are a pivotal factor in ending the pandemic. Thus, through a large-scale population-based study, we investigated the individual-, social-, and family-associated factors affecting the acceptance of COVID-19 vaccines in South Korea. PATIENTS AND METHODS: Data were obtained from a nationwide representative study (Korea Community Health) conducted in 2021. To determine the individual-, social-, and family-associated variables for COVID-19 vaccination acceptance, we investigated data from 225,319 individuals. RESULTS: In the total sample (n=225,319), 184,529 COVID-19-vaccinated people and 40,790 non-vaccinated people were evaluated. The factors related to the acceptance of COVID-19 vaccination were significantly associated with the demographic factors, namely, older age group, female sex, and a history of influenza vaccination, as well as medical conditions such as diabetes, hypertension, and depression. Socioeconomic conditions influencing the acceptance of COVID-19 vaccination were significantly associated with low-income families and blue-collar workers. Health-related risk factors were high in the obese group. However, a noteworthy negative association was found between the acceptance of vaccination and smoking habits and alcohol consumption. Conversely, a positive association was observed between academic level and vaccination acceptance. CONCLUSIONS: Our findings suggest that old age, female sex, a history of influenza vaccination, medical conditions, such as diabetes, hypertension, and depression, low-income families, blue-collar workers, and health-related risk factors, such as obesity, were associated with the acceptance of COVID-19 vaccination. Additionally, a high academic level, absence of smoking habits, and non-current alcohol use were positively associated with vaccine acceptance.

GM-CSF is a marker of compartmentalised intrathecal inflammation in multiple sclerosis.

BACKGROUND: Granulocyte-macrophage colony stimulating factor (GM-CSF) is a pro-inflammatory cytokine secreted by various immune cells. Several studies have demonstrated an expansion of GM-CSF producing T cells in the blood or CSF of people with MS (pwMS). However, whether this equates to greater concentrations of circulating cytokine remains unknown as quantification is difficult with traditional assays. OBJECTIVE: To determine whether GM-CSF can be quantified and whether GM-CSF levels are elevated in pwMS. METHODS: We employed Single Molecule Array (Simoa) to measure GM-CSF in both CSF and blood. We then investigated relationships between GM-CSF levels and measures of blood-CSF-barrier integrity. RESULTS: GM-CSF was quantifiable in all samples and was significantly higher in the CSF of pwMS compared with controls. No association was found between CSF GM-CSF levels and Q-Albumin - a measure of blood-CSF-barrier integrity. CSF GM-CSF correlated with measures of intrathecal inflammation, and these relationships were greater in primary progressive MS compared with relapsing-remitting MS. CONCLUSION: GM-CSF levels are elevated specifically in the CSF of pwMS. Our results suggest that elevated cytokine levels may reflect (at least partial) intrathecal production, as opposed to simple diffusion across a dysfunctional blood-CSF-barrier.

Breakage and Disappearance of a Part of the Midline Catheter Tip During Insertion.

Midline catheters have been proposed as alternatives to central venous catheters and peripherally inserted central catheters. Midline catheters reduce the incidence of overall needle stick injuries during hospitalization, have lower complication rates than central venous catheters or peripherally inserted central catheters, and provide potential cost benefits for hospitals. Complications with midline catheters are similar to those of other intravenous catheters, and intravenous catheter breakage is very rare and invasive. We report a case wherein a midline catheter tip was broken during insertion and removed by open surgery. For the safe use of midline catheters, accurate and delicate insertion techniques should be practiced. More case studies are warranted to verify the usefulness and convenience of various types of midline catheters for their universal use.

METTL3-mediated downregulation of splicing factor SRSF11 is associated with carcinogenesis and poor survival of cancer patients.

OBJECTIVE: N6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications in eukaryotic RNA. As m6A modifications play an important role in RNA processing, abnormal m6A regulation caused by aberrant expression of m6A regulators is closely related to carcinogenesis. In this study, we aimed to determine the role of METTL3 expression in carcinogenesis, regulation of splicing factor expression by METTL3, and their effects in survival period and cancer-related metabolisms. MATERIALS AND METHODS: We investigated the correlation between each splicing factor and METTL3 in breast invasive ductal carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD) and gastric adenocarcinoma (STAD). Survival analysis was performed based on the expression of each splicing factor. To determine the molecular mechanism of SRSF11 in carcinogenesis, gene set enrichment analysis using RNA sequencing data was performed according to SRSF11 expression. RESULTS: Among the 64 splicing factors used for correlation analysis, 13 splicing factors showed a positive correlation with METTL3 in all four cancer types. We found that when METTL3 expression was decreased, the expression of SRSF11 was also decreased in all four types of cancer tissue when compared to that in normal tissue. Decreased SRSF11 expression was associated with poor survival in patients with BRCA, COAD, LUAD, and STAD. Gene set enrichment analysis according to SRSF11 expression showed that the p53/apoptosis, inflammation/immune response, and ultraviolet/reactive oxygen species stimulus-response pathways were enriched in cancers with decreased SRSF11 expression. CONCLUSIONS: These results suggest that METTL3 regulates SRSF11 expression, which could influence mRNA splicing in m6A modified cancer cells. METTL3-mediated downregulation of SRSF11 expression in cancer patients correlates with poor prognosis.

Lactational performance, enteric gas emissions, and plasma amino acid profile of dairy cows fed diets with soybean or canola meals included on an equal protein basis.

This study investigated the effects of feeding solvent-extracted canola meal (CM), extruded soybean meal (ESBM), or solvent-extracted soybean meal (SSBM) on an equivalent crude protein basis on performance, plasma AA profiles, enteric gas emissions, milk fatty acids, and nutrient digestibility in lactating dairy cows. Fifteen Holstein cows (95 ± 20 d in milk) were used in a replicated 3 × 3 Latin square design experiment with 3 periods of 28 d each. Treatments were 3 diets containing 17.1% CM, 14.2% ESBM, or 13.6% SSBM (dry matter basis). Vegetable oil was added (canola oil for CM or soybean oil for SSBM) to equalize the ether extract concentration of the diets. Rumen-protected Met was supplemented targeting digestible Met supply of 2.2% of metabolizable protein in all diets. Canola meal increased dry matter intake (DMI) by 5.9 and 8.9% in comparison with ESBM and SSBM, respectively. Milk urea nitrogen was lowest in CM, followed by SSBM, and was highest for ESBM. No differences were observed in feed efficiency, energy-corrected milk yield, and milk composition or component yields among treatments. Cows fed CM emitted less enteric CH4 per kg of DMI compared with both ESBM and SSBM, but CH4 emission intensity (CH4 per kg of energy-corrected milk) was similar among treatments. In summary, replacement of ESBM or SSBM with CM, on an equal crude protein basis, in the diet of lactating dairy cows enhanced DMI, but yields of energy-corrected milk and milk components and feed efficiency were similar among treatments.

Prediction of venous thromboembolism using clinical and serum biomarker data from a military cohort of trauma patients.

INTRODUCTION: Venous thromboembolism (VTE) is a frequent complication of trauma associated with high mortality and morbidity. Clinicians lack appropriate tools for stratifying trauma patients for VTE, thus have yet to be able to predict when to intervene. We aimed to compare random forest (RF) and logistic regression (LR) predictive modelling for VTE using (1) clinical measures alone, (2) serum biomarkers alone and (3) clinical measures plus serum biomarkers. METHODS: Data were collected from 73 military casualties with at least one extremity wound and prospectively enrolled in an observational study between 2007 and 2012. Clinical and serum cytokine data were collected. Modelling was performed with RF and LR based on the presence or absence of deep vein thrombosis (DVT) and/or pulmonary embolism (PE). For comparison, LR was also performed on the final variables from the RF model. Sensitivity/specificity and area under the curve (AUC) were reported. RESULTS: Of the 73 patients (median Injury Severity Score=16), nine (12.3%) developed VTE, four (5.5%) with DVT, four (5.5%) with PE, and one (1.4%) with both DVT and PE. In all sets of predictive models, RF outperformed LR. The best RF model generated with clinical and serum biomarkers included five variables (interleukin-15, monokine induced by gamma, vascular endothelial growth factor, total blood products at resuscitation and presence of soft tissue injury) and had an AUC of 0.946, sensitivity of 0.992 and specificity of 0.838. CONCLUSIONS: VTE may be predicted by clinical and molecular biomarkers in trauma patients. This will allow the development of clinical decision support tools which can help inform the management of high-risk patients for VTE.

Macrophage secretion of miR-106b-5p causes renin-dependent hypertension.

Myeloid cells are known mediators of hypertension, but their role in initiating renin-induced hypertension has not been studied. Vitamin D deficiency causes pro-inflammatory macrophage infiltration in metabolic tissues and is linked to renin-mediated hypertension. We tested the hypothesis that impaired vitamin D signaling in macrophages causes hypertension using conditional knockout of the myeloid vitamin D receptor in mice (KODMAC). These mice develop renin-dependent hypertension due to macrophage infiltration of the vasculature and direct activation of renal juxtaglomerular (JG) cell renin production. Induction of endoplasmic reticulum stress in knockout macrophages increases miR-106b-5p secretion, which stimulates JG cell renin production via repression of transcription factors E2f1 and Pde3b. Moreover, in wild-type recipient mice of KODMAC/miR106b-/- bone marrow, knockout of miR-106b-5p prevents the hypertension and JG cell renin production induced by KODMAC macrophages, suggesting myeloid-specific, miR-106b-5p-dependent effects. These findings confirm macrophage miR-106b-5p secretion from impaired vitamin D receptor signaling causes inflammation-induced hypertension.

Predictors of permanent stoma creation in patients with mid or low rectal cancer: results of a multicentre cohort study with preoperative evaluation of anal function.

AIM: Preoperative factors predictive of permanent stoma creation were investigated in a long-term follow-up of patients with mid or low rectal cancer. METHOD: We included patients who underwent radical resection for mid or low rectal cancer with available data for preoperative anal function measured by manometry and Faecal Incontinence Severity Index questionnaire between January 2005 and December 2015 in three tertiary referral hospitals. A permanent stoma was defined as a stoma present until the patient's last follow-up visit or death. Preoperative factors that predicted permanent stoma creation were analysed. RESULTS: Over a median follow-up of 57.4 months (range 12-143 months), a permanent stoma was created in 144/577 (25.0%) patients, including 89 (15.4%) who underwent abdominoperineal resection, one (0.2%) who underwent Hartmann's operation without reversal, 15 (2.6%) with a diverting ileostomy at the time of initial sphincter-preserving surgery without undergoing stoma reversal, and 39 (6.8%) who underwent permanent ileostomy formation after sphincter-preserving surgery. Patients with permanent stoma creation had a shorter tumour distance from the anal verge (P < 0.001), larger tumour size (P = 0.020) and higher preoperative Faecal Incontinence Severity Index score (P = 0.020). On multivariable analysis, tumour distance from the anal verge predicted permanent stoma formation (relative risk 0.53 per centimetre increase; 95% confidence interval 0.46-0.60; P < 0.001) but preoperative anal function did not. CONCLUSION: Tumour distance from the anal verge was the only preoperative determinant of permanent stoma creation in rectal cancer patients. These data may help mid and low rectal cancer patients understand the need for permanent stoma.

Effects of 3-nitrooxypropanol on rumen fermentation, lactational performance, and resumption of ovarian cyclicity in dairy cows.

This study examined the effect of 3-nitrooxypropanol (3-NOP), a substance under investigation, on enteric methane (CH4) emission, rumen fermentation, lactational performance, sensory properties of milk, and the resumption of ovarian cyclicity in early-lactation dairy cows. Fifty-six multi- and primiparous Holstein cows, including 8 that were rumen cannulated, were used in a 15-wk randomized complete block design experiment. Cows were blocked based on parity and previous lactation milk yield (MY) or predicted MY, and within each block were randomly assigned to one of 2 treatments: (1) control (CON), administered no 3-NOP, or (2) 3-NOP applied at 60 mg/kg of feed dry matter (3-NOP). Enteric CH4 emission was measured during experimental wk 2, 6, 9, and 15, using the GreenFeed system. Dry matter intake (DMI) and MY data were collected daily throughout the experiment, and milk composition samples were collected 7 times during the experiment. Milk samples were collected from 14 to 60 (±2) d after calving, 3 d per week, and assayed for progesterone concentration to determine resumption of ovarian activity. Compared with CON, 3-NOP decreased daily CH4 emission by 26%, CH4 yield (CH4 per kg of DMI) by 21%, and CH4 emission intensity [CH4 per kg of MY or energy-corrected milk (ECM)] by 25%. Enteric emission of carbon dioxide was decreased by 5%, and hydrogen emission was increased 48-fold by 3-NOP. Inclusion of 3-NOP decreased concentration of total volatile fatty acids (by 9.3%) and acetate but increased butyrate molar proportion, ethanol, and formate concentrations in ruminal fluid. Dry matter intake was lower for 3-NOP compared with CON, but DMI expressed as a percentage of body weight was not different between treatments. Treatment had no effect on milk and ECM, body weight change, or body condition score. Milk composition and milk fat and protein yields were not affected by treatment, except that concentrations of short-chain fatty acids in milk were increased by 3-NOP. Nutrient digestibility and blood metabolites and hormones were not affected by 3-NOP, except that insulin was decreased by 3-NOP. There was no effect of 3-NOP on postpartum resumption of ovarian activity, including days to first and second luteal phases, length of first and second luteal phases, and interval from first to second luteal phase. Sensory properties of milk from cows fed 3-NOP and cheese made from that milk were not affected by treatment. In this experiment, 3-NOP decreased daily enteric CH4 emission, emission yield, and emission intensity, improved feed efficiency, and did not affect lactational performance or onset of ovarian activity in early-lactation dairy cows.

Risk of malignancy in patients with psoriasis: a 15-year nationwide population-based prospective cohort study in Korea.

BACKGROUND: The association between psoriasis and risk of malignancy has not been thoroughly evaluated in a large longitudinal cohort of Asian population. OBJECTIVE: To determine the long-term risk of malignancy in Korean adult patients with psoriasis. METHODS: We conducted a nationwide population-based prospective cohort study with a 15-year observational period. During the baseline period (1997-2000), total 1 773 786 Korean subjects who received health insurance from the National Health Insurance System were enrolled and 5788 subjects were defined as a psoriasis group. The number of new-onset malignancy was collected during the observational period (2001-2015). RESULTS: Patients with psoriasis had a higher adjusted hazard ratio (aHR) for development of overall malignancy [aHR 1.08, 95% confidence interval (CI) 1.00-1.18] and gastric cancer (aHR 1.31, 95% CI 1.08-1.58) compared to controls. The risks of non-Hodgkin lymphoma and non-melanoma skin cancer were significantly increased only in patients with psoriasis who received systemic treatments (aHR 2.86, 95% CI 1.07-7.61 and aHR 3.93, 95% CI 1.47-10.47, respectively). CONCLUSION: Psoriasis is associated with long-term risk for overall malignancy in Koreans, which was primarily driven by the increased risk of gastric cancer.

The outcome following spinal instrumentation in haemodialyzed patients with pyogenic spondylodiscitis.

AIMS: The aim of this study was to evaluate the outcome of spinal instrumentation in haemodialyzed patients with native pyogenic spondylodiscitis. Spinal instrumentation in these patients can be dangerous due to rates of complications and mortality, and biofilm formation on the instrumentation. PATIENTS AND METHODS: A total of 134 haemodialyzed patients aged more than 50 years who underwent surgical treatment for pyogenic spondylodiscitis were included in the study. Their mean age was 66.4 years (50 to 83); 66 were male (49.3%) and 68 were female (50.7%). They were divided into two groups according to whether spinal instrumentation was used or not. Propensity score matching was used to attenuate the potential selection bias. The outcome of treatment was compared between these two groups. RESULTS: A total of 89 patients (66.4%) underwent non-instrumented surgery and 45 (33.5%) underwent instrumented surgery. There were no significant differences in the rates of postoperative complications, except for an increased rate of wound problems in the instrumented group, which was found in the unmatched cohorts (p = 0.034). There were no significant differences in the rate of recurrent infections (p = 0.328 for the unmatched cohort; p = 0.269 for the matched cohort) and mortality rate, including in-hospital (p = 0.713 for the unmatched cohort; p = 0.738 for the matched cohort) and one-year rates (p = 0.363 for the unmatched cohort; p = 0.787 for the matched cohort), between the groups. However, the interval between the initial diagnosis and the first recurrence was significantly longer in the instrumented group (p = 0.008 for the unmatched cohort; p = 0.032 for the matched cohort). CONCLUSION: Instrumented surgery for haemodialyzed patients with pyogenic spondylodiscitis showed similar outcomes, including recurrence and mortality, to non-instrumented surgery, despite the instrumented group having more severe neurological deficit, a larger number of involved levels, and increased kyphotic angle.

A study of contralateral persistent processus vaginalis in laparoscopic hernia repair in children.

PURPOSE: The introduction of laparoscopy for hernia repair permits intra-abdominal observation of a hernia and contralateral persistent processus vaginalis (CPPV). The current study's aim was to investigate the diameter of opening of an inguinal hernia and CPPV in patients with unilateral inguinal hernia, and to evaluate their correlation with age. METHODS: From September 2012 to August 2017, 569 pediatric patients underwent laparoscopic repair of unilateral inguinal hernia. We retrospectively evaluated the size of the hernia and CPPV by measuring the diameter of opening. Pearson correlation analysis and linear-by-linear association were used in the statistical analysis. RESULTS: The median age at operation was 32.4 months (range 0.2-219 months). CPPV was observed in 330 patients (58.0%), and its incidence was significantly higher in patients with left inguinal hernias than in those with right inguinal hernias (62.8 versus 54.0%, p < 0.001). The mean diameter of opening for the hernias was significantly larger than that for CPPV (11.2 ± 3.1 vs. 6.1 ± 2.5 mm, p < 0.001). The incidence of CPPV gradually decreased from 77.2% in infants to 46.6% in the oldest age group (≥ 6 years) (p trend < 0.001). The diameter of the opening of a hernia was not correlated with increasing age, and the diameter of the opening of a CPPV was not correlated with increasing age, as well. CONCLUSION: The diameters of a hernia and CPPV were identified in the current study, and the diameter was not correlated with increasing age. The incidence of CPPV was more common in patients with left inguinal hernias than in those with right inguinal hernias, and it gradually decreased with increasing age.

Efficacy of Ultralow-Dose Valganciclovir Chemoprophylaxis for Cytomegalovirus Infection in ABO-Incompatible Kidney Transplantation Recipients.

BACKGROUND: Cytomegalovirus (CMV) infection can increase morbidity and mortality in kidney transplant (KT) patients. Chemoprophylaxis with valganciclovir (VGCV) is recommended for ABO-incompatible (ABOi) KT patients as it significantly reduces CMV disease and infection. The recommended dose of VGCV for prevention of CMV in a KT recipient is 900 mg once daily, and the treatment duration is 6 months. However, because it is expensive, sufficient amounts might not be administered. METHODS: We investigated whether ultralow-dose VGCV (450 mg every other day) and short dosing period (3 months) was sufficient to prevent CMV infection after ABOi KT. We retrospectively evaluated 74 adult CMV-seropositive donor/CMV-seropositive recipient (D+/R+) ABOi KT recipients from June 2009 to July 2016 who received ultralow-dose VGCV prophylaxis for 3 months. The primary outcome was occurrence of CMV infection. Secondary outcomes were leukopenia and thrombocytopenia. RESULT: All patients received intravenous rituximab 200 mg once and plasmapheresis for reduction of anti-A/B antibodies and interleukin-2 antibodies before undergoing ABOi KT. Mean prophylaxis and follow-up durations were 3 and 52 months, respectively. One patient died of bacterial pneumonia. Four patients lost graft function and were undergoing hemodialysis; 3 cases were caused by antibody-mediated rejection, and 1 was due to mechanical complication after surgery. Fortunately, CMV infection did not occur in any patient. CONCLUSION: Ultralow-dose VGCV is an effective prophylaxis for D+/R+ ABOi KT recipients. Especially, ultralow-dose VGCV CMV infection prevention protocol in Asian populations reduced the side effects and cost.

Application of 3D Fast Spin-Echo T1 Black-Blood Imaging in the Diagnosis and Prognostic Prediction of Patients with Leptomeningeal Carcinomatosis.

BACKGROUND AND PURPOSE: Contrast-enhanced 3D fast spin-echo T1 black-blood imaging selectively suppresses the signal of blood flow and could provide a higher contrast-to-noise ratio compared with contrast-enhanced 3D ultrafast gradient recalled echo (contrast-enhanced gradient recalled echo) and 2D spin-echo T1WI (contrast-enhanced spin-echo). The purpose of our study was to evaluate whether black-blood imaging can improve the diagnostic accuracy for leptomeningeal carcinomatosis compared with contrast-enhanced gradient recalled-echo and contrast-enhanced spin-echo and, furthermore, to determine whether the grade of leptomeningeal carcinomatosis evaluated on black-blood imaging is a significant predictor of progression-free survival. MATERIALS AND METHODS: Leptomeningeal carcinomatosis (n = 78) and healthy (n = 31) groups were enrolled. Contrast-enhanced gradient recalled-echo, contrast-enhanced spin-echo, and black-blood imaging were separately reviewed, and a diagnostic rating (positive, indeterminate, or negative) and grading of leptomeningeal carcinomatosis were assigned. The diagnostic accuracies of the 3 imaging sequences were compared in terms of leptomeningeal carcinomatosis detection. The Kaplan-Meier and the Cox proportional hazards model analyses were performed to determine the relationship between the leptomeningeal carcinomatosis grade evaluated on black-blood imaging and progression-free survival. RESULTS: Black-blood imaging showed a significantly higher sensitivity (97.43%) than contrast-enhanced gradient recalled-echo (64.1%) and contrast-enhanced spin-echo (66.67%) (P < .05). In terms of specificities, we did not find any significant differences among contrast-enhanced gradient recalled-echo (90.32%), contrast-enhanced spin-echo (90.32%), and black-blood imaging (96.77%) (P > .05). A Cox proportional hazards model identified the time to metastasis, Karnofsky Performance Scale status, and a combination of the leptomeningeal carcinomatosis grade with a linear pattern as independent predictors of progression-free survival (P < .05). CONCLUSIONS: Black-blood imaging can improve the diagnostic accuracy and predict progression-free survival in patients with leptomeningeal carcinomatosis.

Safety, tolerability, pharmacodynamics and pharmacokinetics of DWP14012, a novel potassium-competitive acid blocker, in healthy male subjects.

BACKGROUND: A novel potassium-competitive acid blocker, DWP14012, is in clinical development as a potential alternative to proton pump inhibitors for the treatment of acid-related diseases. AIMS: To evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of DWP14012 in humans. METHODS: A randomised, double-blind, double-dummy, placebo- and active-controlled, single- and multiple-ascending dose (SAD and MAD, respectively) study was conducted in healthy male subjects without Helicobacter pylori infection. Subjects randomly received a single oral dose of 10-320 mg DWP14012, esomeprazole (active comparator) or placebo in the SAD study (n = 72) and once daily doses of 20-160 mg DWP14012, esomeprazole or placebo for 7 days in the MAD study (n = 48; 8:2:2). Tolerability was evaluated using a microRNA-122 assay. Pharmacodynamics were evaluated through 24-hour gastric pH monitoring, and pharmacokinetics were evaluated plasma and urine DWP14012 concentrations. RESULTS: DWP14012 was generally well tolerated. The liver toxicity of DWP14012 was not higher than that of placebo after multiple oral administrations. DWP14012 showed rapid and sustained suppression of gastric acid secretion for 24 hours after dosing. Clear dose-response and exposure-response relationships were observed. Plasma concentrations of DWP14012 increased in a dose-proportional manner in the MAD study, whereas in the SAD study, DWP14012 did not significantly accumulate in the plasma. CONCLUSIONS: DWP14012 was well tolerated, and showed a rapid and long-lasting gastric acid suppression effect in healthy subjects. These results justify further investigation of DWP14012 in patients with acid-related disorders.