Long-term clinical outcomes of aspirin-exacerbated respiratory disease: Real-world data from an adult asthma cohort.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a phenotype of severe asthma, but its disease course has not been well documented compared with that of aspirin-tolerant asthma (ATA). OBJECTIVES: This study aimed to investigate the long-term clinical outcomes between AERD and ATA. METHODS: AERD patients were identified by the diagnostic code and positive bronchoprovocation test in a real-world database. Longitudinal changes in lung function, blood eosinophil/neutrophil counts, and annual numbers of severe asthma exacerbations (AEx) were compared between the AERD and the ATA groups. Within a year after baseline, two or more severe AEx events indicated severe AERD, whereas less than two AEx events indicated nonsevere AERD. RESULTS: Among asthmatics, 353 had AERD in which 166 and 187 patients had severe and nonsevere AERD, respectively, and 717 had ATA. AERD patients had significantly lower FEV1%, higher blood neutrophil counts, and higher sputum eosinophils (%) (all p < .05) as well as higher levels of urinary LTE4 and serum periostin, and lower levels of serum myeloperoxidase and surfactant protein D (all p < .01) than those with ATA. In a 10-year follow-up, the severe AERD group maintained lower FEV1% with more severe AEs than the nonsevere AERD group. CONCLUSION AND CLINICAL RELEVANCE: We demonstrated that AERD patients presented poorer long-term clinical outcomes than ATA patients in real-world data analyses.

Arsenite-induced cytotoxicity is regulated by p38-SQSTM1/p62 and JNK-BNIP3L/Nix signaling in lung cancer cells.

Arsenic is a potent carcinogen in humans. However, the molecular mechanisms underlying its toxicity in lung cancer remain unclear. Here, we report that arsenite-induced cytotoxicity is regulated by SQSTM1/p62 and BNIP3L/Nix signaling in non-small-cell lung cancer H460 cells. Arsenite exposure resulted in dose-dependent growth inhibition, which was associated with apoptosis, as demonstrated by depolarized mitochondrial membrane potential and cleavage of caspase-8, caspase-3, PARP-1, and Bax. The autophagy adaptor p62 was detected in the monomeric and multiple high-molecular-weight (HMW) forms, and protein levels were upregulated depending on both arsenite concentrations (≤45 µM) and exposure times (<24 h). LC3-II, an autophagy marker, was upregulated as early as 1 h after arsenite treatment. Expression of Nix, a mitochondrial outer membrane protein, continued to increase with arsenite concentration and exposure time; it was detected in the monomeric and multiple HMW forms. Soon after arsenite exposure, p62 colocalized with Nix in the cytoplasm, and p62 knockdown reduced the Nix levels and increased the LC3-II levels. In contrast, Nix knockdown did not affect the p62 and LC3-II levels but reduced caspase-8, caspase-3, and Bax cleavage, indicating that Nix accumulation resulted from its reduced autophagic degradation and promoted apoptosis. p38 inhibition markedly increased arsenite-induced Nix protein and reduced p62 protein levels, resulting in increased autophagy and apoptosis. Furthermore, c-Jun NH2-terminal kinase inhibition reduced Nix and Bax cleavage, and both signaling pathways were suppressed by N-acetylcysteine treatment. Our results suggest that arsenite-induced cytotoxicity is modulated by the coordinated action of p62 and Nix through MAPK.

Autophagy-mediated cytoplasmic accumulation of p53 leads to apoptosis through DRAM-BAX in cadmium-exposed human proximal tubular cells.

The tumor suppressor p53 is involved in cadmium (Cd)-induced apoptosis and autophagy. However, the regulatory mechanisms of p53 in Cd-induced kidney injury are not well established. Here, we report the role of autophagy in Cd-induced p53 induction in human proximal tubular cells (HK-2). HK-2 cells treated with Cd induced the expression of p53, DNA damage autophagy modulator (DRAM), and Bcl-2-associated X protein (BAX), as well as caused poly [ADP-ribose] polymerase 1 (PARP-1) cleavage. Cd exposure also induced autophagy with the accumulation of monomeric p62 and multiple high molecular weight form (HMW)-p62. The expression levels of p53, p62, microtubule-associated protein 1A/1B-light chain 3 (LC3)-1, and LC3-II were similar in the sense that they increased up to 12 h and then gradually decreased. DRAM and BAX levels began to increase post autophagy induction and continued to increase, indicating that autophagy preceded apoptosis. While the genetic knockdown of p53 downregulated HWM-p62, DRAM, and BAX, the expression levels of these proteins were upregulated by p53 overexpression. The genetic knockdown of p62 downregulated p53, autophagy, DRAM, and BAX. The inhibition of autophagy through pharmacological and genetic knockdown reduced p53 and inhibited Cd-induced apoptosis. Collectively, Cd induces apoptosis through p53-mediated DRAM-BAX signaling, which can be regulated by autophagy.

Risk Factors for Beyond Milan Recurrence After Hepatic Resection for Single Hepatocellular Carcinoma No Larger Than 5 Centimeters.

Hepatic resection (HR) is considered a treatment of choice for a single hepatocellular carcinoma (HCC) ≤5 cm in patients with preserved liver function. However, it is possible for these patients to develop a severe form of recurrence (beyond Milan recurrence [BMR] criteria). This recurrence could have been avoided if liver transplantation (LT) was performed primarily, as LT is believed to yield a more favorable oncological outcome compared with HR. The aim of this study was to determine the risk factors for BMR after HR and to verify whether primary LT can provide a more favorable outcome in patients with BMR risk factors. Data from 493 patients who underwent HR for HCC ≤5 cm between 1995 and 2016 were analyzed. Among them, 74 patients (15%) experienced BMR. The 10-year survival rate of patients with BMR was significantly low compared with that of patients without BMR (22.6% versus 79.8%; P < 0.01). In multivariate analysis, calculated hepatic venous pressure gradient ≥7 mm Hg and microvascular invasion were identified as the risk factors for BMR (P < 0.05). During the same period, 63 eligible patients underwent LT as a primary treatment for HCC ≤5 cm. No significant difference in long-term survival rate was observed when no risk factor for BMR was present in the HR and LT groups (85.5% versus 100%; P = 0.39). However, 10-year survival was poorer in the HR group in the presence of risk factors for BMR (60.6% versus 91.8%; P < 0.001). Among the patients with HCCs ≤5 cm, which are resectable and transplantable, LT is indicated when calculated hepatic venous pressure gradient ≥7 mm Hg and/or microvascular invasion is present.

Persistence and Adherence of Anticholinergics and Beta-3 Agonist for the Treatment of Overactive Bladder: Systematic Review and Meta-Analysis, and Network Meta-Analysis.

PURPOSE: We aimed to investigate the persistence and adherence rate of overactive bladder medications and factors that affect these rates. MATERIALS AND METHODS: We conducted electronic English-language literature searches of the PubMed®, Cochrane Library, and EMBASE® databases from the earliest available date of indexing through May 21, 2019 using the Medical Subject Headings (MeSH) terms and EMBASE subject headings (Emtree). Primary measurement outcomes were overall persistence and adherence rate at 6, 12, 24, and 36 months in anticholinergics and mirabegron. Secondary outcomes were individual effect of each medication on persistence and adherence rate at 12 months, and moderating factors affecting the overall persistence and adherence rate at 12 months. RESULTS: Pooled overall persistence rate at 12 months of overactive bladder medications of anticholinergics and mirabegron was 0.218 (95% CI: 0.197-0.240). The pooled overall persistence rate at 12 months was 0.402 (95% CI: 0.277-0.528) in mirabegron, 0.249 (95% CI: 0.182-0.316) in solifenacin, and 0.220 (95% CI: 0.078-0.361) in fesoterodine. Overall adherence rate of overactive bladder medications of anticholinergics and mirabegron was 0.589 (95% CI: 0.507-0.670). The pooled overall adherence rate at 12 months was 0.654 (95% CI: 0.528-0.781) in mirabegron, 0.784 (95% CI: 0.588-0.980) in solifenacin, 0.782 (95% CI: 0.652-0.911) in fesoterodine, and 0.679 (95% CI: 0.651-0.707) in imidafenacin. Persistence and adherence rates were associated with age, gender, anticholinergic exposure history, type of medication, study type, and study year. CONCLUSIONS: Persistence and adherence rates were lower than previously reported and were associated with certain clinical and demographic factors.

Early removal of central venous catheter may not impact the in-hospital mortality in patients with acute leukemia.

Central venous catheters (CVCs) are generally required for chemotherapy in patients with acute leukemia, but catheter-related infection is one of the common causes of neutropenic fever. We investigated the in-hospital mortality according to early removal of CVCs and the factors influencing the mortality in patients with acute leukemia undergoing remission induction chemotherapy. This study retrospectively analyzed the hospital record data of 278 patients with acute leukemia treated with non-tunneled CVCs and remission induction chemotherapy in a single institution. Bloodstream infection was more common (p < 0.0001) and median peak C-reactive protein (CRP) levels after neutropenic fever were significantly higher (23.3 vs. 14.5 mg/dl, p = 0.003) in the group with early removal than in the group with maintenance of the CVC. Multivariate analysis of the patients revealed a significant decrease in the mortality with female gender (odds ratio (OR): 0.19, 95% confidence interval (CI): 0.06-0.54, p = 0.002) and a significant increase in the mortality according to the peak CRP (OR 1.12, 95% CI: 1.07-1.17, p < 0.0001). By contrast, early removal of the CVC had no significant effect on the mortality (OR = 1.16, 95% CI: 0.54-2.47, p = 0.706) in univariate analysis. Furthermore, subsequent bloodstream infection after clinical decision for maintenance or early removal of the CVC was confirmed more frequently in the group with early removal (early removal, 22.6%; maintenance, 7.6%, p < 0.0001). Early removal of the CVC had no benefit regarding the mortality and prophylaxis of bloodstream infection in patients with acute leukemia undergoing remission induction chemotherapy. Therefore, maintaining a CVC for as long as possible may be considered, if catheter-related bloodstream infection is not strongly suspected.

Prostate cancer specific mortality after 5α-reductase inhibitors medication in benign prostatic hyperplasia patients: systematic review and meta-analysis.

BACKGROUND: Our study was conducted to investigate the effect of 5-ARI on the death rate from prostate cancer by means of an updated meta-analysis using related data. METHODS: We did comprehensive literature searches using the PubMed, Embase, and Cochrane databases through July 2019. We evaluated the risk of bias in such studies using the ROBINS-I tool and analyzed deaths from cancer and deaths from all causes using HR. RESULTS: The meta-analysis included 11 studies. The pooled overall HRs for cancer-specific deaths between 5-ARI treatment versus non-exposed groups were 0.937 (95% CI: 0.730, 1.201). In the subgroup moderator analysis, the number of patients and additional medication variables were significantly associated with deaths from all causes (p = 0.022 and p = 0.005, respectively). For detecting the publication bias or small-study effect in the included studies, we performed Begg and Mazumdar's correlation test (0.851 and 0.573) and Egger's regression coefficient test (0.035 and 0.245) and ​suggested that there was no evidence of publication bias or small-study effect in this meta-analysis. CONCLUSIONS: Our study indicated that exposure to 5-ARI had no close association between the overall death rate or cancer-specific deaths. To confirm these results, well-designed prospective studies with large samples are required.

Protective effects of non-thermal plasma on triethylene glycol dimethacrylate-induced damage in odontoblast-like MDPC-23 cells.

AIM: To evaluate whether the use of non-thermal plasma (NTP) could reduce triethylene glycol dimethacrylate (TEGDMA)-mediated damage in MDPC-23 cells. METHODOLOGY: The effects of NTP and TEGDMA on MDPC-23 cell proliferation were tested using WST-1 assays after pretreatment with NTP for 1 min and exposure to TEGDMA. Live/Dead assays were used to visualize cell death. To monitor the effects of NTP and TEGDMA on the cell cycle and apoptotic cell death, flow cytometry was performed. Western blotting was used to assess changes in protein levels mediated by NTP and TEGDMA treatment, and enzyme-linked immunosorbent assays were performed to evaluate the effects of NTP and TEGDMA on prostaglandin E2 (PGE2 ) expression. One-way analysis of variance and Duncan's post hoc tests were used for statistical analysis. RESULTS: NTP treatment effectively protected cells from TEGDMA-mediated cell damage and blocked TEGDMA-mediated cell growth inhibition (p < .05). NTP appeared to protect cells from death (p < .05) and blocked TEGDMA-mediated apoptotic cell death. Additionally, NTP reduced TEGDMA-mediated apoptotic activation of poly (ADP) ribose polymerase-1 and caspase-3 (p < .05). Furthermore, NTP effectively reduced TEGDMA-mediated expression of cyclooxygenase-2 and PGE2 proteins by inhibiting nuclear factor-κB protein expression (p < .05). CONCLUSIONS: NTP alleviated TEGDMA-mediated adverse effects by reducing cytotoxicity and inflammatory reactions in cells exposed to TEGDMA.

Trabecular Bone Score Is a Useful Parameter for the Prediction of Vertebral Fractures in Patients With Polymyalgia Rheumatica.

INTRODUCTION: Polymyalgia rheumatica (PMR), a benign rheumatic disorder, requires long-term glucocorticoid therapy, which could be associated with osteoporosis. In the present study, we compared bone mineral density (BMD), trabecular bone score (TBS) and frequencies of vertebral fracture (VF) among patients with PMR or rheumatoid arthritis (RA) and controls. METHODS: Fifty-three postmenopausal women with PMR aged 50 yr or older were eligible for inclusion in this study. Subjects in RA (n = 106) and control (n = 106) groups were selected by propensity score matching with controlling age, body mass index and use of anti-osteoporotic agents. RESULTS: The frequency of VF in patients with PMR (30.2%) was significantly higher than those in patients with RA (13.2 %) and controls (13.2%, p = 0.017). The mean TBS of patients with PMR (1.317 ± 0.092) was significantly lower than those of patients with RA (1.336 ± 0.089) and the controls (1.373 ± 0.073, p < 0.001). In receiver operating characteristic analysis for VF in patients with PMR, the area under the curve (AUC) was 0.759 (95% confidence interval [CI] = 0.601-0.918, p < 0.001) for TBS and 0.618 (95% CI = 0.442-0.795, p < 0.001) for L-spine BMD. The AUCs were 0.760 (95% CI = 0.630-0.891, p ≤ 0.001) and 0.767 (95% CI 0.627-0.907, p < 0.001) for femur neck and total hip BMD, respectively. Multivariate analysis identified the factor associated with VF of patients with PMR as a lower TBS (Odds ratio: 0.000, 95% CI: 0.000, 0.754, p = 0.043). CONCLUSION: TBS could be a supplementary tool for discriminating osteoporotic fractures in postmenopausal patients with PMR.

Multivariate analyses of MRI findings for predicting osteomyelitis of the foot in diabetic patients.

BACKGROUND: There have been no previous magnetic resonance imaging (MRI) studies using multivariable analysis to diagnose osteomyelitis in patients with diabetic foot. PURPOSE: To retrospectively investigate the MRI findings of osteomyelitis in patients with diabetic foot using multivariate analyses. MATERIAL AND METHODS: From November 2015 to March 2018, 118 patients who underwent MRI of the foot to evaluate suspected osteomyelitis were included in this study. The patients were categorized into the presence or absence of osteomyelitis. The primary and secondary MRI findings were retrospectively reviewed. To identify independent predictive MRI findings, multivariate analyses with binary logistic regression and receiver operating characteristic curve analyses were performed including all 118 patients and 93 patients presenting decreased T1 signal intensity, respectively. RESULTS: T1 signal intensity, T1 marrow pattern, T1 marrow distribution, T2 signal intensity, concordance of marrow signal intensity, cortical interruption, ulcer depth, abscess, and wet gangrene were significantly different between the two groups (P < 0.05). Multivariate analyses indicated that fluid equivalent T2 signal intensity, deep ulcer, and confluent T1 marrow pattern were major factors associated with osteomyelitis. The area under the curve of predicted probabilities for the combination of these factors was 0.799 across all 118 patients and 0.761 across 93 patients with decreased T1 signal intensity. CONCLUSION: Confluent T1 marrow pattern is a reliable finding to suggest osteomyelitis in patients with diabetic foot. In addition, fluid equivalent T2 signal intensity and deep ulcer are important findings that may suggest osteomyelitis, irrespective of T1 signal intensity change.

Association between lower urinary tract symptoms and cardiovascular risk scores in ostensibly healthy women.

OBJECTIVES: To investigate the association between lower urinary tract symptoms (LUTS) and cardiovascular disease (CVD) risk in women, as severe LUTS are known to be associated with CVD risk in men but few studies have focused on this issue in women. SUBJECTS AND METHODS: A total of 1014 ostensibly healthy women, who participated in a voluntary health check in a health promotion centre from November 2013 to October 2015, were enrolled. LUTS were assessed using the International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS). CVD risk scores were calculated using the Framingham risk score and the American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease (ASCVD) score. Correlation, partial correlation, and multiple logistic regression analyses were conducted. RESULTS: The mean age and body mass index (BMI) of the women were 51 years and 22.6 kg/m2 , respectively. The ASCVD score showed significant positive correlations with IPSS items Question 2 (Q2), Q3, Q5, and Q7 (all P < 0.05), total IPSS (P = 0.001), IPSS storage (P = 0.006) and IPSS voiding symptoms scores (P = 0.001) based on partial correlation analysis after adjustment for BMI. For the OABSS, the ASCVD score showed significant positive correlations with OABSS items Q2, Q3, and Q4 (P < 0.001, P = 0.017, and P < 0.001, respectively) and total OABSS (P < 0.001). Multiple logistic regression analysis showed that the moderate-severe risk groups of the OABSS and IPSS were associated with the ASCVD risk score in adjusted models (P < 0.001) compared to the none-mild OABSS and mild IPSS groups. After adjustment for age and BMI, IPSS storage score was significantly related with the ASCVD risk score (B = 0.855, P = 0.016) CONCLUSIONS: LUTS, especially storage symptoms, might be risk factors for predicting future CVD risk in women. Further prospective or cohort studies are needed to validate this possibility.

Real-life effectiveness of inhaler device switch from dry powder inhalers to pressurized metred-dose inhalers in patients with asthma treated with ICS/LABA.

BACKGROUND AND OBJECTIVE: Mixed inhaler device use for asthma is associated with worse inhaler technique and outcomes. Given that relievers are commonly prescribed as pressurized metred-dose inhalers (pMDI), changing preventers from dry powder inhalers (DPI) to pMDI may improve asthma outcomes. This study aimed to assess the persistence and effectiveness of switching from DPI to pMDI for inhaled corticosteroid and long-acting ß2 -agonist combination therapy (ICS/LABA). METHODS: This was a historical cohort study using Ajou University Hospital (Korea) patient records. Persistence of switch was defined as receiving ≥1 pMDI and no DPI after the switch. Effectiveness of switch was assessed as the proportion without severe asthma exacerbation and the proportion achieving risk domain asthma control (RDAC; no asthma-related hospitalization, antibiotics without upper respiratory diagnosis or acute course of oral corticosteroids) and overall asthma control (OAC; RDAC and ≤ 200 µg salbutamol/≤500 µg terbutaline average daily dose) comparing 1 year after and before the switch. RESULTS: Within 85 patients who switched from DPI to pMDI and persisted for a year, higher proportion were free from asthma exacerbation after the switch (mean difference in proportion = 0.129, 95% CI: 0.038-0.220). Switching to pMDI was also associated with better RDAC (75.3% vs 57.7%, P = 0.001) and OAC (57.7% vs 45.9%, P = 0.021). From the entire 117 patients who switched to fixed-dose combination (FDC)/ICS LABA pMDI, 76.1% (95% CI: 69.0-100.0%) patients persisted in the following 6 months. CONCLUSION: Switching to and persisting with pMDI was associated with decreased asthma exacerbations and improved asthma control. The majority of patients persisted with the switch to pMDI for ICS/LABA treatment.

Longterm Analysis of Biliary Complications After Duct-to-Duct Biliary Reconstruction in Living Donor Liver Transplantations.

Biliary complication (BC) is still regarded as the Achilles' heel of a living donor liver transplantation (LDLT). This study aims to evaluate the longterm outcomes of the duct-to-duct (DD) biliary reconstruction using 7-0 suture and to identify the risk factors of BCs after LDLTs. Data of 140 LDLTs between 2006 and 2015 were analyzed. All biliary reconstructions were performed as DD anastomoses using 7-0 suture: 102 for the right lobe, 20 for the left lobe, and 18 for right posterior sector grafts. BC was defined as a bile leakage (BL) or a biliary stricture (BS), and the median follow-up time after LDLT was 65 months. A total of 19 recipients (13.5%) developed BCs (8 BLs and 16 BSs) after LDLT. The survival rates between recipients with and without BCs were 83% and 86.7%, respectively (P = 0.88). In univariate analyses, the risk factors for BC were small diameter of the graft's bile duct, long warm ischemic time, small graft-to-recipient weight ratio, and no use of external biliary stent (EBS). The graft's bile duct diameter ≤ 3 mm and no use of EBS were determined as independent risk factors (hazard ratios of 9.74 and 7.68, respectively) in multivariate analyses. The 116 recipients with EBS had no BL, 11 had BSs (9%), while 24 without EBS had 8 BLs (33%) and 5 BSs (21%). After a propensity score match between the recipients with and without EBS, the EBS group (24) developed only 1 BS (4%). In conclusion, DD anastomosis using 7-0 suture combined with EBS could provide favorable longterm outcomes after LDLT, which should thus be considered the surgical technique of choice for LDLTs.

Macroscopic and local approaches of phase transition in sol-gel synthesized (Bi0.5Na0.5)TiO3-SrTiO3 thin films.

High-quality (1 - x)(Bi0.5Na0.5)TiO3-xSrTiO3 lead-free piezoelectric thin films (x = 0, 0.1, and 0.25) on Pt(111)/Ti/SiO2/Si(100) substrates were prepared by a sol-gel method. The microstructures of the thin films as a function of SrTiO3 doping level and temperature were investigated by X-ray diffraction and Raman spectroscopy. Their temperature- and frequency-dependent piezoelectric properties were studied on the nanoscale using switching spectroscopy piezoresponse force microscopy (SS-PFM). A rhombohedral ferroelectric to pseudocubic relaxor phase transition was observed when either ST content or temperature increased. The significant frequency dependence of both ferroelectric and piezoelectric properties was also disclosed by analyzing polarization hysteresis loops on the macroscopic scale and local switching dynamics at various frequencies. It was determined that the short-range order clusters came out through the long-range ferroelectric order, thus the nanoscale approaches are consistent with macroscopic data at elevated temperatures and various frequency ranges.

MAPK/JNK1 activation protects cells against cadmium-induced autophagic cell death via differential regulation of catalase and heme oxygenase-1 in oral cancer cells.

Antioxidant enzymes are related to oral diseases. We investigated the roles of heme oxygenase-1 (HO-1) and catalase in cadmium (Cd)-induced oxidative stress and the underlying molecular mechanism in oral cancer cells. Exposing YD8 cells to Cd reduced the expression levels of catalase and superoxide dismutase 1/2 and induced the expression of HO-1 as well as autophagy and apoptosis, which were reversed by N-acetyl-l-cysteine (NAC). Cd-exposed YD10B cells exhibited milder effects than YD8 cells, indicating that Cd sensitivity is associated with antioxidant enzymes and autophagy. Autophagy inhibition via pharmacologic and genetic modulations enhanced Cd-induced HO-1 expression, caspase-3 cleavage, and the production of reactive oxygen species (ROS). Ho-1 knockdown increased autophagy and apoptosis. Hemin treatment partially suppressed Cd-induced ROS production and apoptosis, but enhanced autophagy and CHOP expression, indicating that autophagy induction is associated with cellular stress. Catalase inhibition by pharmacological and genetic modulations increased Cd-induced ROS production, autophagy, and apoptosis, but suppressed HO-1, indicating that catalase is required for HO-1 induction. p38 inhibition upregulated Cd-induced phospho-JNK and catalase, but suppressed HO-1, autophagy, apoptosis. JNK suppression exhibited contrary results, enhancing the expression of phospho-p38. Co-suppression of p38 and JNK1 failed to upregulate catalase and procaspase-3, which were upregulated by JNK1 overexpression. Overall, the balance between the responses of p38 and JNK activation to Cd appears to have an important role in maintaining cellular homeostasis via the regulation of antioxidant enzymes and autophagy induction. In addition, the upregulation of catalase by JNK1 activation can play a critical role in cell protection against Cd-induced oxidative stress.

Propacetamol poses a potential harm of adverse hypotension in male and older patients.

PURPOSE: Researchers recently suggested intravenous paracetamol as a potential cause of hypotension. We aimed to investigate risk factors of paracetamol- and propacetamol-associated adverse drug reactions (ADRs) in Korean individuals. METHODS: All adverse hypotension cases, regardless of suspected drug, and all ADRs associated with paracetamol and propacetamol use were collected from the Korea Adverse Event Reporting System database between 2011 and 2014. The seriousness, causality, and type of ADR were classified. RESULTS: Of 4,771 cases of adverse hypotension, 403 (8.4%) were reported to be related to propacetamol. This was comparable to the rate of hypotension associated with fentanyl (454, 9.5%), the major suspected drug of hypotension. Paracetamol-associated hypotension accounted for merely 1.2% (55 cases) of all hypotension cases. Among ADRs associated with propacetamol use, hypotension was the most common (37.1%), whereas cutaneous reactions were the primary paracetamol-associated ADR. Propacetamol/paracetamol-associated hypotension was frequently recorded in older patients (≥54 years) (53.9 ± 25.8 vs. 42.8 ± 21.7, P < 0.001) and taking more concomitant drugs (1.9 ± 5.0 vs. 1.1 ± 3.2, P < 0.001). Also, compared with other ADRs associated by propacetamol/paracetamol, hypotension was more commonly assessed as a serious outcome (27.3% vs. 11.4%, P < 0.001). Regarding concomitant medications, the risk for hypotension associated with propacetamol was significantly increased in patients simultaneously taking antibacterials (J01), cold preparations (R05), drugs for acid related disorders (A02), blood substitutes (B05), or antithrombotics (B01). CONCLUSIONS: Propacetamol was found to be a major suspected drug of pharmacologically associated hypotension in Korea. Older and male patients taking medications in combination with propacetamol/paracetamol should undergo monitoring of their blood pressure. Copyright © 2017 John Wiley & Sons, Ltd.

Intravoxel incoherent motion diffusion-weighted magnetic resonance imaging of focal vertebral bone marrow lesions: initial experience of the differentiation of nodular hyperplastic hematopoietic bone marrow from malignant lesions.

OBJECTIVE: To evaluate the ability of intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) parameters to differentiate nodular hyperplastic hematopoietic bone marrow (HHBM) from malignant vertebral bone marrow lesions (VBMLs). MATERIALS AND METHODS: A total of 33 patients with 58 VBMLs, including 9 nodular HHBM lesions, 39 bone metastases, and 10 myelomas, were retrospectively assessed. All diagnoses were confirmed either pathologically or via image assessment. IVIM diffusion-weighted MRI with 11 b values (from 0 to 800 s/mm2) were obtained using a 3.0-T MR imager. The apparent diffusion coefficient (ADC), pure diffusion coefficient (D), perfusion fraction (f), and pseudodiffusion coefficient (D*) were calculated. ADC and IVIM parameters were compared using the Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performances of ADC, D, f, and D* in terms of VBML characterization. The diagnostic performance of morphological MR sequences was also assessed for comparison. RESULTS: The ADC and D values of nodular HHBM were significantly lower than those of malignant VBML (both p values < 0.001), whereas the f value was significantly higher (p < 0.001). However, there were no significant differences in D* between the two groups (p = 0.688). On ROC analysis, the area under the curve (AUC) for D was 1.000, which was significantly larger than that for ADC (AUC = 0.902). CONCLUSION: Intravoxel incoherent motion diffusion-weighted MRI can be used to differentiate between nodular HHBM and malignant VBML. The D value was significantly lower for nodular HHBM, and afforded a better diagnostic performance than the ADC, f, and D* values in terms of such differentiation.

Quantitative Assessment of the Portal Pressure for the Liver Surgery Using Serological Tests.

OBJECTIVE: To establish a reliable equation to predict hepatic venous pressure gradient (HVPG) using serological tests for surgical patients with hepatocellular carcinoma (HCC). BACKGROUND: Accurate assessment of portal pressure for surgical patients with HCC is important for safe hepatic resection (HR). The HVPG is regarded as the most reliable method to detect portal hypertension. However, HVPG is not utilized in many medical centers due to invasiveness of procedure. METHODS: Between 2006 and 2008, 171 patients (Correlation cohort), who underwent liver surgery in a tertiary hospital, were enrolled. Preoperative measurements of the HVPG and serological tests were performed simultaneously. Correlation between the HVPG and serological tests were analyzed to establish an equation for calculated HVPG (cHVPG). Between 2008 and 2013, 510 surgical patients (Application cohort) were evaluated, and HR recommended when cHVPG < 10 mm Hg. The outcomes of HR were analyzed to evaluate reliability of the cHVPG for HR. RESULTS: In the correlation cohort, the equation for cHVPG was established using multivariate linear regression analysis; cHVPG (mm Hg) = 0.209 × [ICG-R15 (%)] - 1.646 × [albumin (g/dL)] - 0.01×[platelet count (10)] + 1.669 × [PT-INR] + 8.911. In the application cohort, 425 patients with cHVPG < 10 mm Hg underwent HR. Among them, 357 had favorable value of ICG-R15 < 20% (group A), and 68 had unfavorable value of ICG-R15 ≥ 20% (group B). There was no significant difference in patient demographics, tumor characteristics, operative outcome, and survival rates between group A and B. CONCLUSIONS: The equation for cHVPG of this study was established on statistical reliability. The cHVPG could be useful to predict portal pressure quantitatively for surgical patients with HCC using serological tests.

Altered Systemic Adipokines in Patients with Chronic Urticaria.

BACKGROUND: Increasing evidence suggests that adipokines affect immune responses and chronic urticaria (CU) is associated with an altered immune response related to chronic systemic inflammation. Our objectives were to investigate whether adipokines are involved in CU pathogenesis and to outline relationships between adipokines and urticaria severity and quality of life. METHODS: Serum adiponectin, leptin, lipocalin-2 (LCN2), interleukin (IL)-10, IL-6, and tumor necrosis factor (TNF)-α concentrations were measured by enzyme-linked immunosorbent assays in 191 CU patients and 89 healthy controls. The effect of LCN2 on N-formyl-methionine-leucine-phenylalanine (fMLP)-induced neutrophil chemotaxis was assessed using migration assays. CU severity was assessed based on the urticaria activity score (UAS). To explore relationships between adipokines and UAS and the chronic urticaria-specific quality of life (CU-QoL) questionnaire, a structural equation model was used. RESULTS: Mean levels of serum LCN2, TNF-α, IL-6, and IL-10 were significantly higher in CU patients than in controls. Adiponectin levels were significantly lower in patients with CU than in controls. While serum IL-6 levels were significantly higher in refractory CU patients, compared to responsive CU individuals, LCN2 levels were significantly lower. LCN2 inhibited fMLP-induced neutrophil migration. LCN2 showed a direct relationship with UAS (ß = -0.274, p < 0.001), and UAS was found to contribute to CU-QoL (ß = 0.417, p < 0.001). CONCLUSIONS: Our results highlighted an imbalance in pro- and anti-inflammatory adipokines in CU patients. We suggest that LCN2 could be a differential marker for disease activity and the clinical responses to antihistamine treatment in CU patients. Modulation of systemic inflammation may be a therapeutic strategy for treating severe, refractory CU.

Evaluation of Adhesive Capsulitis of the Shoulder With Fat-Suppressed T2-Weighted MRI: Association Between Clinical Features and MRI Findings.

OBJECTIVE: The purpose of this study was to examine the association between clinical features and MRI findings in adhesive capsulitis of the shoulder. MATERIALS AND METHODS: This study included 103 patients (41 men, 62 women) with adhesive capsulitis. The MRI findings were correlated with pain intensity, range of motion, and clinical stage. Joint capsule edema in the axillary recess, extracapsular edema, obliteration of the subcoracoid fat triangle, and effusion in the long head biceps tendon sheath were assessed by two radiologists using fat-suppressed T2-weighted images. Joint capsule thickness in the axillary recess and degree of external rotation during MRI were also measured. Intraclass correlation coefficient and kappa values were obtained. Associations between MRI findings and clinical features were assessed by statistical analyses. RESULTS: Anterior extracapsular edema was associated with range of motion on external rotation and abduction (p < 0.01). Joint capsule edema in the humeral portion of the axillary recess was associated with range of motion on external rotation (p = 0.01). Joint capsule thickness in the humeral portion of the axillary recess and height of the axillary recess were associated with pain intensity (p < 0.05). Joint capsule edema in the humeral portion of the axillary recess and obliteration of the subcoracoid fat triangle were significantly more common in the early stages of adhesive capsulitis (p < 0.05). Joint capsule thickness in the humeral portion of the axillary recess at stage 1 (4.67 ± 1.73 mm) was significantly different from the thickness at the later stages (stage 2, 3.73 ± 1.49 mm; stages 3 and 4, 3.67 ± 1.44 mm) (p < 0.05). CONCLUSION: MRI is useful for assessing clinical impairment and predicting the clinical stage of adhesive capsulitis.