The purpose of this phase I clinical trial is to assess the safety and tolerability of allogeneic adipose tissue‐derived stem cells (ADSCs) among chronic kidney disease (CKD) patients. 12 eligible ...CKD patients with an estimated glomerular filtration rate (eGFR) of 15–44 ml/min/1.73 m2 received one dose of intravenous allogeneic ADSCs (ELIXCYTE®), as 3 groups: 3 low dose (6.4 × 107 cells in total of 8 ml), 3 middle dose (19.2 × 107 cells in total of 24 ml) and 6 high dose (32.0 × 107 cells in total of 40 ml) of ELIXCYTE® and evaluated after 48 weeks. Primary endpoint was the safety profiles in terms of incidence of adverse events (AEs) and serious adverse event (SAE). Two subjects in high dose group experienced a total of 2 treatment‐related AEs which are Grade 1 slow speech and Grade 1 bradyphrenia after the infusion. One subject in middle dose group experienced an SAE unlikely related to treatment, grade 2 proteinuria. No fatal AE was reported in this study. An increase in eGFR was observed in 7 out of 12 subjects (58%) at Week 24 and in 6 of 12 subjects (50%) by Week 48. By Week 24, an increase in eGFR by more than 20% among all CKD patients with baseline eGFR ≧ 30 ml/min/1.73 m2 as compared to only 2 subjects in baseline eGFR < 30 ml/min/1.73 m2 group. No significant reduction in proteinuria was noted among all subjects. This phase I trial demonstrated single‐dose intravenous ELIXCYTE was well tolerated in moderate‐to‐severe CKD patients and its preliminary efficacy warrants future studies.
We have previously demonstrated calcimimetics optimize the balance between osteoclastic bone resorption and osteoblastic mineralization through upregulating Wingless and int-1 (Wnt) signaling ...pathways in the mouse and cell model. Nonetheless, definitive human data are unavailable concerning therapeutic effects of Cinacalcet on chronic kidney disease and mineral bone disease (CKD-MBD) and osteoclast-osteoblast interaction. We aim to investigate whether Cinacalcet therapy improves bone mineral density (BMD) through optimizing osteocytic homeostasis in a human model. Hemodialysis patients with persistently high intact parathyroid hormone (iPTH) levels > 300 pg/mL for more than 3 months were included and received fixed dose Cinacalcet (25 mg/day, orally) for 6 months. Bone markers presenting osteoclast-osteoblast communication were evaluated at baseline, the 3rd and the 6th month. Eighty percent of study patients were responding to Cinacalcet treatment, capable of improving BMD, T score and Z score (16.4%, 20.7% and 11.1%, respectively). A significant correlation between BMD improvement and iPTH changes was noted (
= -0.26,
< 0.01). Nonetheless, baseline lower iPTH level was associated with better responsiveness to Cinacalcet therapy. Sclerostin, an inhibitor of canonical Wnt/β-catenin signaling, was decreased from 127.3 ± 102.3 pg/mL to 57.9 ± 33.6 pg/mL. Furthermore, Wnt-10b/Wnt 16 expressions were increased from 12.4 ± 24.2/166.6 ± 73.3 pg/mL to 33.8 ± 2.1/217.3 ± 62.6 pg/mL. Notably, procollagen type I amino-terminal propeptide (PINP), a marker of bone formation and osteoblastic activity, was increased from baseline 0.9 ± 0.4 pg/mL to 91.4 ± 42.3 pg/mL. In contrast, tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), a marker of osteoclast activity, was decreased from baseline 16.5 ± 0.4 mIU/mL to 7.7 ± 2.2 mIU/mL. Moreover, C-reactive protein levels were suppressed from 2.5 ± 0.6 to 0.8 ± 0.5 mg/L, suggesting the systemic inflammatory burden may be benefited after optimizing the parathyroid-bone axis. In conclusion, beyond iPTH suppression, our human model suggests Cinacalcet intensifies BMD through inhibiting sclerostin expression and upregulating Wnt-10b/Wnt 16 signaling that activates osteoblastic bone formation and inhibits osteoclastic bone resorption and inflammation. From the perspective of translation to humans, this research trial brings a meaningful insight into the osteoblast-osteoclast homeostasis in Cinacalcet therapy for CKD-MBD.
Hyperuricemia has been proven to be an independent risk factor for chronic kidney disease (CKD). However, the role of hyperuricemia in the progression of CKD remains unclear. Thus, we performed a ...systematic review and meta-analysis to evaluate the efficacy and safety of febuxostat, a first line urate-lowering agent, in CKD patients with hyperuricemia.
We have systematically searched for randomized controlled trials assessing the efficacy and safety of febuxostat versus control in CKD patients with hyperuricemia through MEDLINE, PubMed, EMBASE, and Cochrane databases. All statistical analyses were conducted by using the statistical package Review Manager, version 5.3.5. Heterogeneity was assessed using the Cochrane Q and I tests and summary statistics were reported with 95% confidence interval. Two-tailed test was used for analysis and a P value of <.05 is considered statistically significant.
Eleven eligible trials with 1317 participants were included in the meta-analysis. A significant reduction in serum uric acid was found in the febuxostat treated group. Also, a significant higher eGFR was found in the febuxostat treated group among CKD stage 3 and 4 patients. No significant difference of major complication or death was identified between treatment and control groups.
The meta-analysis showed that other than its urate-lowering effect, febuxostat presented a reno-protective effect in CKD patients. More studies with larger sample sizes and higher quality are required to clarify the role of febuxostat use in the progression of CKD.
The immunosuppressant agents in kidney transplantation (KT) may lead to various complications such as opportunistic infections and malignancies. BK virus associated nephropathy is a significant ...complication following KT, and it can result in graft failure. BK virus causes tubulointerstitial nephritis, ureter stenosis, and even graft failure in KT recipients with impaired immune system. We described a 63-year-old woman, who was a hepatitis C carrier and on dialysis for 22 years before KT, who received cadaveric-donor KT 2 years previously. She reported decreasing urine output and general weakness. The serum creatinine level was slightly increased from 2.94 to 4.38 mg/dL.
Immunosuppressant medications including prednisolone, everolimus, cyclosporin, and mycophenolate sodium were continued as maintenance therapy post KT. Kidney biopsy was performed due to deterioration of graft function.
The kidney biopsy showed consistent results with early-stage polyomavirus nephropathy, characterized by focal viral cytopathic changes with positive immunohistochemical signals and mesangial proliferative glomerulonephritis, immune-complex-mediated (Fig 1 and Fig 2). Negative C4d staining at peritubular capillary was reported. The dosage of mycophenolate sodium was tapered from 720 to 360 mg daily and that of everolimus increased from 0.5 to 1.0 mg daily due to BK viral infection with BK nephropathy. The serum creatinine level was 2.75 mg/dL after treatment.
Early detection of BK nephropathy and decreasing immunosuppressant agents are the mainstay of treatment. Substituting leflunomide for mycophenolate sodium and increasing dosage of everolimus has been proposed to solve BK nephropathy. We presented that the use of leflunomide in such situation is in a timely manner.
•BK virus causes tubulointerstitial nephritis and graft failure in kidney transplant recipients.•Substituting leflunomide for mycophenolate sodium is proposed to solve BK nephropathy.•Timely decreasing immunosuppressant agents are the mainstay of treatment.
Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir–ritonavir, and ...ribavirin for treating patients with COVID-19.
This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688.
Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3–7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days IQR 5–11) than the control group (12 days 8–15; hazard ratio 4·37 95% CI 1·86–10·24, p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir–ritonavir because of biochemical hepatitis. No patients died during the study.
Early triple antiviral therapy was safe and superior to lopinavir–ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted.
The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.
To adopt a healthy lifestyle is considered an essential component of nursing education. Self-rated health is a subjective assessment of health status and is consistent with objective health status. ...Previous studies have shown an association between self-rated health and engagement in a healthy lifestyle. Nursing students need to feel good about their subjective health status and to be able to adopt health improvements in their lifestyle before attempting to disseminate health messages to clients. The aims of this study were to compare the difference in self-rated health and health promotion lifestyle profile between senior and junior nursing students, describe correlations between self-rated health and health promotion lifestyle profile, and identify the predictors of self-rated health.
A cross-sectional descriptive survey was adopted. The study sample consisted of 314 junior and senior year nursing students from a tertiary institution. The self-reported questionnaire consisted of a single-item question to examine their self-rated health. The Health Promoting Lifestyle Profile-II: Chinese version short form (HPLP-IICR) was used to investigate the health-promoting lifestyles of the students. Descriptive statistics, Mann-Whitney U test, Chi-square test, Fisher's exact test, Spearman's correlation, and ordinal logistic regression were used to analyze the data.
The median scores for self-rated health were 3 (Mean 3.26, IQR 3-4) and 3 (Mean 3.19, IQR 3-4) out of 5 for Year 2 and Year 5 students, respectively, with no significant difference between the two groups. The two groups of students showed no significant differences in overall score and in most subscales of the HPLP-IICR. An ordinal logistic regression showed that those students with higher health management score (OR: 1.12, 95% CI: 1.04-1.21) and who had experienced no family conflicts in the recent month than having family conflict (OR: 1.64, 95% CI: 1.01-2.66) were more likely to have higher self-rated health.
Nursing education and clinical practice can undoubtedly increase the health knowledge of students, but may not lead to changes in actual health-promoting behaviours. Students with a higher health management score and no family conflicts are more likely to give a positive appraisal of their health status.
Increasing evidence has shown that immune surveillance is compromised in a tumor-promoting microenvironment for patients with non-small cell lung cancer (NSCLC), and can be restored by appropriate ...chemotherapy.
To test this hypothesis, we analyzed microarray gene expression profiles of peripheral blood mononuclear cells from 30 patients with newly-diagnosed advanced stage NSCLC, and 20 age-, sex-, and co-morbidity-matched healthy controls. All the patients received a median of four courses of chemotherapy with cisplatin and gemcitabine for a 28-day cycle as first line treatment.
Sixty-nine differentially expressed genes between the patients and controls, and 59 differentially expressed genes before and after chemotherapy were identified. The IL4 pathway was significantly enriched in both tumor progression and chemotherapy signatures. CXCR4 and IL2RG were down-regulated, while DOK2 and S100A15 were up-regulated in the patients, and expressions of all four genes were partially or totally reversed after chemotherapy. Real-time quantitative RT-PCR for the four up-regulated (S100A15, DOK2) and down-regulated (TLR7, TOP1MT) genes in the patients, and the six up-regulated (TLR7, CRISP3, TOP1MT) and down-regulated (S100A15, DOK2, IL2RG) genes after chemotherapy confirmed the validity of the microarray results. Further immunohistochemical analysis of the paraffin-embedded lung cancer tissues identified strong S100A15 nuclear staining not only in stage IV NSCLC as compared to stage IIIB NSCLC (p = 0.005), but also in patients with stable or progressive disease as compared to those with a partial response (p = 0.032). A high percentage of S100A15 nuclear stained cells (HR 1.028, p = 0.01) was the only independent factor associated with three-year overall mortality.
Our results suggest a potential role of the IL4 pathway in immune surveillance of advanced stage NSCLC, and immune potentiation of combination chemotherapy. S100A15 may serve as a potential biomarker for tumor staging, and a predictor of poor prognosis in NSCLC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It has been demonstrated that the traditional Chinese medicine rikkunshito, ameliorates anorexia in several types of human cancer and attenuates lung injury by inhibiting neutrophil infiltration. The ...current study investigated the clinical and hematological effects of rikkunshito and its underlying mechanisms of action in the treatment of advanced non-small cell lung cancer (NSCLC). The Illumina microarray BeadChip was used to analyze the whole-genome expression profiles of peripheral blood mononuclear cells in 17 patients with advanced NSCLC. These patients were randomized to receive combination chemotherapy (cisplatin and gemcitabine) with (n=9, CTH+R group) or without (n=8, CTH group) rikkunshito. The primary endpoint was the treatment response and the categories of the scales of anorexia, nausea, vomiting and fatigue; secondary endpoints included the hematological effect and whole genome gene expression changes. The results of the current study indicated that there were no significant differences in clinical outcomes, including treatment response and toxicity events, between the two groups. Median one-year overall survival (OS) was 12 months in the CTH group and 11 months in the CTH+R group (P=0.058 by log-rank test), while old age (>60 years old) was the only independent factor associated with one-year OS (hazard ratio 1.095, 95% confidence interval, 1.09-1.189, P=0.030). Patients in the CTH+R group experienced significantly greater maximum decreases in both white cell count (P=0.034) and absolute neutrophil count (P=0.030) from the baseline. A total of 111 genes associated with neutrophil apoptosis, the cell-killing ability of neutrophils, natural killer cell activation and B cell proliferation were up-regulated following rikkunshito treatment. A total of 48 genes associated with neutrophil migration, coagulation, thrombosis and type I interferon signaling were down-regulated following rikkunshito treatment. Rikkunshito may therefore affect the blood neutrophil count when used with combination chemotherapy in patients with NSCLC, potentially by down-regulating prostaglandin-endoperoxidase synthase 1, MPL, AMICA1 and junctional adhesion molecule 3, while up-regulating elastase, neutrophil expressed, proteinase 3, cathepsin G and cluster of differentiation 24.
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