The Efficacy of Budesonide, Levocabastine, and Their Combination in Treatment of Vasomotor Rhinitis.

INTRODUCTION: Relevant studies have demonstrated that glucocorticoids and antihistamines, such as budesonide and azelastine, are effective in the treatment of vasomotor rhinitis, with their combined use being more effective than that of a single drug. The aim of this study was to assess the improvement in the symptoms of patients following the combined administration of these drugs. METHODS: We conducted a single-center randomized study on 42 patients. Participants were randomly treated with budesonide, levocabastine hydrochloride, or their combination for 2 weeks. The visual analog scale (VAS) score and levels of eosinophil cationic protein (ECP), histamine (HA), leukotriene B4 (LTB4), and vasoactive intestinal peptide (VIP) in nasal secretions were evaluated before and after treatment. RESULTS: The symptoms of patients were improved in all 3 treatment groups compared with those before treatment. Following combined treatment, the improvement in symptoms of nasal obstruction, runny nose, nasal itching, and sneezing was much greater than those in the groups treated with budesonide or levocabastine hydrochloride alone (p = 0.04, 0.004, 0.005, 0.004, respectively). The decreased levels of these inflammatory mediators were significantly different between the different treatment groups. CONCLUSIONS: Budesonide or levocabastine hydrochloride alone improved the nasal symptoms of patients with vasomotor rhinitis and reduced the levels of ECP, HA, LTB4, and VIP in nasal secretions. However, their combination improved the symptoms of patients more significantly than each drug alone.

Altered serum metabolome associated with vascular calcification developed from CKD and the critical pathways.

Introduction: Vascular calcification (VC) is more likely to be detected in the chronic kidney disease (CKD) population. The mechanism of VC development from CKD is different from that for simple VC and has always been a major research area. The aim of this study was to detect alterations in the metabolome during development of VC in CKD and to identify the critical metabolic pathways and metabolites involved in its pathogenesis. Methods: Rats in the model group were given an adenine gavage combined with a high-phosphorus diet to imitate VC in CKD. The aorta calcium content was measured and used to divide the model group into a VC group and non-vascular calcification group (non-VC group). The control group was fed a normal rat diet and given a saline gavage. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to determine the altered serum metabolome in the control, VC, and non-VC groups. The identified metabolites were mapped into the Kyoto Encyclopedia of Genes and Genomes (KEGG) database (https://www.genome.jp/kegg/) for pathway and network analyses. Result: There were 14 metabolites that changed significantly in the VC group, with three metabolic pathways playing critical roles in the pathogenesis of VC in CKD: steroid hormone biosynthesis; valine, leucine and isoleucine biosynthesis; and pantothenate and CoA biosynthesis. Conclusion: Our results indicated changes in the expression of steroid sulfatase and estrogen sulfotransferase, and down-regulation of the in situ synthesis of estrogens in the VC group. In conclusion, the serum metabolome alters significantly during the pathogenesis of VC in CKD. The key pathways, metabolites, and enzymes we identified are worth further study and may become a promising therapeutic target for the treatment of VC in CKD.

Bibliometric analysis of fibroblast growth factor 21 research over the period 2000 to 2021.

Background: Fibroblast growth factor 21 (FGF-21) is an evolutionarily conserved protein that plays multiple roles in metabolic regulation. Over the past two decades, numerous studies have deepened our understanding of its various functions and its pharmacological value. Nevertheless, most clinical trials have not achieved the desired results, which raises issues regarding its clinical value. In this bibliometric analysis, we evaluated the state of FGF-21 research over the last 20 years and identified important topics, achievements, and potential future directions. Methods: Publications related to FGF-21 were collected from the Web of Science Core Collection-Science Citation Index Expanded. HistCite, VOSviewer, and CiteSpace were used for bibliometric analysis and visualization, including the analysis of annual publications, leading countries, active institutions and authors, core journals, co-cited references, and keywords. Results: Altogether, 2,490 publications related to FGF-21 were obtained. A total of 12,872 authors from 2,628 institutions in 77 countries or regions reported studies on FGF-21. The United States of America was the most influential country in FGF-21 research. Alexei Kharitonenkov, Steven A. Kliewer, and David J. Mangelsdorf were the most influential scholars, and endocrinology journals had a core status in the field. The physiological roles, clinical translation, and FGF-21-based drug development were the main topics of research, and future studies may concentrate on the central effects of FGF-21, FGF-21-based drug development, and the effects of FGF-21 on non-metabolic diseases. Conclusion: The peripheral metabolic effects of FGF-21, FGF-21-based drug development, and translational research on metabolic diseases are the three major topics in FGF-21 research, whereas the central metabolic effects of FGF-21 and the effects of FGF-21 on metabolic diseases are the emerging trends and may become the following hot topics in FGF-21 research.

The Role of 12/15-Lipoxygenase and Its Various Metabolites Generated from Multiple Polyunsaturated Fatty Acids as Substrates in Inflammatory Responses.

12/15-lipoxygenase (12/15-LOX) is a member of the lipoxygenase family, which can catalyze a variety of polyunsaturated fatty acids (PUFA) to produce different metabolites, such as 12-hydroxyeicosatetraenoic acid (12-HETE), 15-HETE, lipoxin (LX), hepoxilin, resolvin, protectin, and maresins. 12/15-LOX and its metabolites take part in inflammatory responses and mediate related signalling pathways, playing an essential role in various inflammatory diseases. So the definition, catalytic substrates, metabolites of 12/15-lipoxygenase, and their roles in inflammatory responses are reviewed in this article.

Predictive significance of arachidonate 15-lipoxygenase for eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) exhibits a poorer outcome compared with non-eosinophilic chronic rhinosinusitis with nasal polyps (nonECRSwNP), so it is significant to identify effective markers to differentiate ECRSwNP in guiding the treatment strategies of these patients. Although arachidonate 15-lipoxygenase (ALOX15) is positioned as a marker of eosinophilic inflammation, its study in differentiating ECRSwNP has not been reported. The aim of this study is to assess the potential of ALOX15 in distinguishing and predicting ECRSwNP. METHODS: Forty-eight patients with chronic rhinosinusitis with nasal polyps (CRSwNP), including 30 ECRSwNP and 18 nonECRSwNP patients, were enrolled. ALOX15 mRNA level was determined in polyps by real-time polymerase chain reaction (RT-PCR). The patients' baseline characteristics were evaluated and analyzed for correlations with ALOX15. Receiver operating characteristic (ROC) curve was used to assess the predictive significance of the potential predictors for ECRSwNP. RESULTS: ALOX15 mRNA level was significantly higher in ECRSwNP patients than in nonECRSwNP patients (P < 0.001). ALOX15 mRNA was significantly correlated with tissue and blood eosinophil percentages (r = 0.565, P < 0.001 and r = 0.395, P = 0.006), olfaction scores (r = 0.400, P = 0.005), total visual analogue scale (VAS) symptom scores (r = 0.383, P = 0.007), ethmoid/maxillary sinus (E/M) ratio (r = 0.463, P = 0.001), and endoscopy scores (r = 0.409, P = 0.004). Logistic regression analysis showed ALOX15 mRNA level and percentage of blood eosinophils to be predictive factors for ECRSwNP (P = 0.004 and P = 0.036, respectively). ROC curve indicated ALOX15 to have high predictive accuracy for ECRSwNP (area under the curve (AUC) = 0.909), which was further improved by combination of ALOX15 with percentage of blood eosinophils (AUC = 0.933). CONCLUSIONS: The relative ALOX15 mRNA level alone or in combination with blood eosinophils might be a reliable biomarker for predicting a diagnosis of ECRSwNP.

Catheter-related complications and survival among incident hemodialysis patients in Singapore.

INTRODUCTION:: Hemodialysis is the main modality of renal replacement therapy in Singapore. However, a majority of the patients in Singapore are initiated on hemodialysis via a catheter. This study examines the complication rates and factors predicting catheter-related bloodstream infections and mortality rates in patients who were initiated on hemodialysis at our institution. METHODS:: This is a single-center retrospective analysis of incident hemodialysis patients who were initiated on renal replacement therapy between 1 January 2010 and 31 December 2012. Catheter-related bloodstream infection risk factors, organisms, and associated mortality were analyzed. RESULTS:: The catheter-related bloodstream infection and exit site infection incidence rates were 0.75 and 0.50 per 1000 catheter days, respectively. The mean duration to first catheter-related bloodstream infection episode was 182.47 ± 144.04 catheter days. Prolonged catheter duration was found to be a risk factor for catheter-related bloodstream infection. Compared to patients initiated on dialysis via arteriovenous fistula, initiation of dialysis via catheter is strongly associated with increased mortality (6.0% vs 14.5%; p = 0.02). In particular, the presence of diabetes mellitus and development of catheter-related bloodstream infection was associated with increased mortality ( p = 0.04 and 0.05, respectively). In addition, patients who began hemodialysis before being seen by a nephrologist were associated with decreased mortality (3.4% vs 13.0%; p = 0.03). CONCLUSION:: In conclusion, prolonged duration of catheter insertion is found to be a risk factor for catheter-related bloodstream infection in hemodialysis patients, and its development is associated with increased mortality. Early referral to a nephrologist and creation of arteriovenous fistula in pre-end-stage renal disease patients are pivotal in improving the outcomes of patients.

Outcomes of arteriovenous fistula creation, effect of preoperative vein mapping and predictors of fistula success in incident haemodialysis patients: A single-centre experience.

AIM: Vascular access in haemodialysis is critical for effective therapy. We aim to evaluate the outcomes of arteriovenous fistula (AVF) creation in incident haemodialysis patients, impact of preoperative vein mapping and predictors of successful AVF maturation in our centre. METHODS: Data of End-stage Renal Disease (ESRD) patients initiated on haemodialysis from January 2010 to December 2012 in our centre were retrospectively obtained from electronic medical records and clinical notes. Demographic characteristics, medical comorbidities, perioperative details were collected, and patients were followed up until 1 January 2014. RESULTS: A total of 708 patients (median age 64, IQR 55-72) were included with mean duration of follow up of 2.3 ± 1.2 years, with access of AVF and arteriovenous graft (AVG) in 694 (98%) and 14 (2%) patients respectively. Eight patients were lost to follow-up. Successful AVF maturation was achieved in 542 patients (78%), with 1-year cumulative patency rate of 74%. Multivariate analysis revealed male gender, upper arm AVF and good postoperative thrill and pulse as predictors of successful AVF maturation. Preoperative vein mapping was performed in 42.5% (295/694) of patients, with mean vein diameter of 2.44 ± 0.82 mm. Maturation rates with and without vein mapping were 72.2% and 82.4%, respectively, (P = 0.001). In patients with vein diameters of <2 mm and ≥2 mm, there was no statistically significant difference in maturation rates (71.3% vs. 72.6%; P = 0.887) and median maturation time (66 vs. 78 days; P = 0.73). CONCLUSION: Arteriovenous fistula can be successfully created in most incident haemodialysis patients. Routine vein mapping is not necessary if veins are suitable on physical examination alone, and vein sizes of <2 mm on ultrasound is not associated with lower AVF maturation rate.

Time delay and its effect on survival in malaysian patients with non-small cell lung carcinoma.

While evidence indicates that early stage disease has better prognosis, the effect of delay in presentation and treatment of patients with non-small cell lung cancer (NSCLC) on survival is debatable. A retrospective study of 122 Malaysian patients with NSCLC was performed to examine the presentation and treatment delay, and its relation with patient survival. Median (25-75% IQR) interval between onset of symptoms and first hospital consultation (patient delay) and between first hospital consultation and treatment or decision to treat (doctor delay) were 2 (1.0- 5.0) and 1.1 (0.6-2.4) months respectively. The median survival rates in patient delay of <1, 1 to 3, and >3 months were 4.1 (9.9-1.7), 5.1 (10.9-3.2) and 5.7 (12.3-2.1) months respectively (log rank p=0.648), while in doctor delay, <30, 30-60, >60 days, the rates were 4.1 (10.8-1.8), 7.6 (13.7-3.2) and 5.3 (16.0-3.0) months respectively (p=0.557). Most patients presented and were treated in a relatively short time, and delays did not appear to influence survival. This Asian data is consistent with those from Western population, reiterating the need for public health measures that can identify disease early..

Survival in Patients with Non-Small Cell Lung Cancer Who Opted out of Cancer-Specific Therapy.

In Malaysia, many patients opted out of cancer-specific treatment for various reasons. This study was undertaken to investigate the survival rate of patients with stages I to III non-small cell lung cancer (NSCLC) who opted out of treatment, compared with those who accepted treatment. Case records of 119 patients diagnosed with NSCLC between 1996 and 2003 in two urban-based hospitals were retrospectively examined. Survival status was ascertained from follow-up medical clinic records or telephone contact with patients or their next-of-kin. Median (25-75% IQR) survival rate for 79 patients who accepted and 22 patients who opted out of treatment, were 8.6 (16.0-3.7) and 2.2 (3.5-0.8) months respectively [log rank p< 0.001, Kaplan-Meier survival analysis]. Except for proportionately more patients with large cell carcinoma who declined treatment, there was no significant difference between the two groups in relation with age, gender, ethnicity, tumour stage, and time delays between symptom onset and treatment or decision-to-treat. We concluded that there was a small but significant survival benefit in accepting cancer-specific treatment. The findings imply that there is no effective alternative therapy to cancer-specific treatment in improving survival. However, overall prognosis for patients with NSCLC remains dismal.