Risk and dose-response relationship of diabetes mellitus for endophthalmitis after cataract surgery in a nationwide cohort study in Taiwan.

BACKGROUND: To investigate the risk of endophthalmitis after cataract surgery in patients with diabetes mellitus (DM) and evaluate the dose-response relationship. METHODS: This retrospective cohort study enrolled patients who underwent bilateral cataract surgeries from 2000 to 2017 in Taiwan National Health Insurance Research Database. The endophthalmitis rates within 3 months after cataract surgery were compared between DM and non-DM cohorts using a generalised estimating equation. The diabetes complications severity index (DSCI) score was adopted to assess the dose-response effect on the endophthalmitis rate. RESULTS: A total of 883 398 patients (1 766 796 eyes) were included. Patients with DM had an increased risk of endophthalmitis after cataract surgery than patients without DM (0.261% vs. 0.242%, adjusted odds ratio = 1.09, 95% confidence interval = 1.03-1.16). The higher endophthalmitis rate in the DM group than in the non-DM group remains after excluding those with prior vitrectomy or intravitreal injection (IVI), and took IVI between the cataract surgery and endophthalmitis (p = 0.0156, 0.0048, and 0.0139). There was a significant dose-response relationship on the likelihood of endophthalmitis in DM patients when DCSI score >10. The endophthalmitis rate is highest among DM complications in patients with metabolic disorders (0.342%). CONCLUSION: DM was a risk factor for endophthalmitis after cataract surgery after adjusting for age, sex, common systemic disorders, and excluding those with prior vitrectomy or IVI and having IVI between cataract surgery and endophthalmitis. A dose-response relationship was noted in DM patients with a DCSI score >10.

Safety of the endovascular aneurysm repair procedure: real-world evidence using interrupted-time series analysis.

OBJECTIVES: In Taiwan, endovascular aneurysm repair for treating abdominal aortic aneurysms (AAA) was introduced in 2004 and became reimbursable in February 2010. We evaluated the real-world practice and safety of endovascular aneurysm repair in Taiwan. METHODS: Patients who underwent repair operations for AAA (open or endovascular) from 2000 to 2016 were enrolled (n = 11485). Outcome statistics (during the index hospitalization: length of stay, rate of ischaemic bowel disease and 30-day mortality; after discharge: 30-day readmission rate, 2-year mortality, 2-year reintervention rate and 2-year paraplegia rate) were calculated for each half-year cohort. Propensity score-based stabilized weights were used to balance covariates among each half-year cohort. Interrupted time-series analysis was then performed. RESULTS: The elective and emergency ratio of AAA repair was 50:50 from 2000 to 2004 and became 60:40 from 2010 to 2016. The half-year rate of endovascular aneurysm repair was 0% in 2000 to 2004/06, 83.16% in 2010 and 98.1% in 2016. Interrupted time series analysis revealed that after endovascular aneurysm repair became reimbursable, both elective and emergency groups had a reduction in length of stay (-4.2 days, P < 0.0001; -1.5 days, P = 0.0928) and 30-day mortality (-5.22%, P = 0.0702; -7.76%, P = 0.0086) but a significant increase in the reintervention rate (5.05%, P = 0.0031; 4.36%, P = 0.0097). CONCLUSIONS: Endovascular aneurysm repair was predominantly used in treating AAAs after it was reimbursed in Taiwan. Endovascular aneurysm repair is efficacious regarding short-term outcomes but increased the 2-year reintervention rate in both groups.

Clinical features and outcomes of anti-neutrophil cytoplasmic autoantibody-associated vasculitis in Chinese childhood-onset patients.

Data on anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) are limited in children. This study is to determine the clinical features and outcomes of childhood-onset AAV. A retrospective study was performed on patients who were diagnosed with AAV before 18 years old in Xiangya Hospital. Their medical records were analyzed by retrospective review. Sixteen patients were diagnosed with AAV before 18 years old in the past 9 years, with an average age of 13.3 ± 3.3 years and 13 of them were female. There were 15 patients with microscopic polyangiitis (MPA) and 1 with Wegener's granulomatosis. The interval between onset of disease and diagnosis of AAV was 2 (1.5-3) months. Most patients (15/16, 93.8%) had multi-organ involvement, and all patients had renal involvement with 7 (43.8%) patients requiring dialysis at presentation. Eleven patients underwent a renal biopsy, of which mixed class and sclerotic class were the most two common histological types. All patients received immunosuppressive therapy for induction therapy including intravenous administrations of methylprednisolone (MP) pulse therapy for 8 patients. 8 patients (50%) achieved remission after induction therapy. After a median follow-up of 46.3 ± 36.1 months, nine (56.3%) patients progressed to end-stage renal disease (ESRD) and 5 (31.3%) patients died. Childhood-onset AAV showed similar clinical and pathological features compared to those of adults, except that it usually occurs in girls. The most commonly involved organ was the kidney, and it had a high risk of progression to ESRD. Early diagnosis and initiation of appropriate immunomodulatory therapy would be important to improve outcomes.

Glomerular Immune Deposition in MPO-ANCA Associated Glomerulonephritis Is Associated With Poor Renal Survival.

Background: Rapidly progressive glomerulonephritis caused by antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is typically characterized as pauci-immune glomerulonephritis. However, immune complex (IC) deposition in the glomerulus has been reported in a growing number of studies. Here, we assess the presence of glomerular immune deposits alongside renal outcome in myeloperoxidase (MPO)-ANCA associated glomerulonephritis (MPO-ANCA GN). Methods: Clinical and histopathologic characteristics of 97 patients with MPO-ANCA GN classified by renal biopsy from January 2008 to December 2019 were extracted retrospectively from electronic medical records. The extent of immune deposits in the kidney (C3, C4, C1q, IgA, IgG, IgM) at diagnosis were analyzed by immunofluorescence (IF). Patients were followed up for a median period of 15 months. The response to treatment and outcomes of renal and histological lesion changes were also assessed. Results: In our study, 41% (40/97) of patients showed positive IF (≥2+) for at least one of the six immunoglobulin or complement components tested. Patients with IC deposits showed higher levels of serum creatinine (p=0.025), lower platelet counts (p=0.009), lower serum complement C3 (sC3) (≤790 ml/L) (p=0.013) and serum IgG (p=0.018) than patients with pauci-immune (PI) deposition at diagnosis. End-stage renal disease was negatively associated with eGFR (HR 0.885, 95% CI 0.837 to 0.935, p<0.0001), platelet count (HR 0.996, 95% CI 0.992 to 1.000, p=0.046) and serum globulin (HR 0.905, 95% CI 0.854 to 0.959, p=0.001). Patients with lower sC3 levels showed a worse renal outcome than the patients with normal sC3 at diagnosis (p=0.003). Analysis of the components of the renal deposits found that patients with IgG deposits exhibited a poorer renal outcome compared to patients that were IgG negative (p=0.028). Moreover, Bowman's capsule rupture occurred less frequently in patients with IgM deposition compared with IgM negative counterparts (p=0.028). Vascular lesions and granuloma-like lesions had been seen more frequently in cases with IgA deposition than those without IgA deposition (p=0.03 and 0.015, respectively). Conclusion: In conclusion, patients with immune complex deposits in the kidney showed less platelet count, lower sC3 and sIgG levels, and higher serum creatinine levels. Patients with low sC3 at initial and with continued low sC3 during the treatment displayed a trend toward poorer kidney survival. Moreover, the IC group showed a worse renal outcome than the PI group, further enforcing the present strategy of introducing complement targeted therapies in AAV.

Inhibition of Rho-kinase alleviates peritoneal fibrosis and angiogenesis in a rat model of peritoneal dialysis.

BACKGROUND/AIMS: The present study investigated whether Rho-kinase inhibition had a therapeutic role on the pathogenesis of peritoneal fibrosis and angiogenesis. METHODS: A rat model of peritoneal dialysis was induced by a daily intraperitoneal infusion of 4.25% Dianeal. Those rats were treated with Rho-kinase inhibitor, fasudil. Immunofluorescence, Western blot and RT-PCR were used to detect the expression of TGF-ß1, Collagen I, αSMA and VEGF in each group. Microvessel density (MVD) was measured by immunohistochemistry. Rho-kinase activity was determined by western immunoblotting. RESULTS: Rho-kinase was activated in the peritoneum of the PD group, which was inhibited by fasudil. Compared with PD group, the mRNA and protein expressions of TGF-ß1, αSMA and Collagen I were significantly downregulated in fasudil treatment groups in a dose-dependent manner, and the expression of VEGF and peritoneal MVD was also significantly downregulated in fasudil treatment groups in a dose-dependent manner. CONCLUSION: The Rho-kinase was activated in the peritoneum of the peritoneal dialysis rats, and the inhibition of Rho-kinase by fasudil can remarkably decrease peritoneal fibrosis and angiogenesis.

Smad7 gene transfer attenuates angiogenesis in peritoneal dialysis rats.

AIM: Transforming growth factor-ß (TGF-ß) has been shown to play a role in peritoneal angiogenesis associated with peritoneal dialysis (PD). The present study investigated whether blockade of TGF-ß signalling with Smad7 has a therapeutic effect on PD induced-peritoneal angiogenesis. METHODS: A rat model of peritoneal dialysis was induced by a daily intraperitoneal injection of 4.25% Dianeal and lipopolysaccharides. PD rats were transfected with a doxycycline regulated, Smad7-expressing plasmid using an ultrasound-microbubble-mediated system on day 0 and day 14 after initiation of PD and an empty vector was used as control. Peritoneal microvessel density (MVD) in peritoneal tissue was assessed by anti-CD31 immunohistochemistry after 4 weeks of PD and peritoneal angiogenic growth factors, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) was also examined by immunofluorescence, western blot and reverse transcription-polymerase chain reaction. RESULTS: In contrast to the normal control group, at 4 weeks after PD, PD rats displayed peritoneal lesions, peritoneal angiogenesis and increased mRNA and protein expression of VEGF, bFGF and PDGF. Smad7 gene transfer significantly attenuated the peritoneal MVD and inhibited the upregulation of VEGF, bFGF and PDGF. Moreover, inhibition of peritoneal angiogenesis by overexpression of Smad7 was associated with inhibition of phosphorylation of Smad3 and downregulation of TGF-ß expression. CONCLUSION: Smad7 gene transfer via an ultrasound-microbubble-mediated system is able to attenuate peritoneal angiogenesis in a rat model of PD. Those results suggest that blockade of the TGF-ß/Smad signalling pathway may represent a novel therapeutic approach to prevent PD-induced peritoneal angiogenesis.

Fibroblast growth factor-23 and interleukin-6 are risk factors for left ventricular hypertrophy in peritoneal dialysis patients.

BACKGROUND: Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular death in dialysis patients. Fibroblast growth factor-23 (FGF-23) and interleukin-6 (IL-6) were thought to be related to cardiovascular diseases (CVDs) in dialysis. METHODS: To determine the relationship between FGF-23, IL-6 and LVH in continuous ambulatory peritoneal dialysis (CAPD) patients, serum FGF-23 and IL-6 levels as well as standard laboratory parameters were assessed in 62 CAPD patients and 30 healthy controls. LVH was determined by echocardiography in dialysis patients. RESULTS: Serum FGF-23 and IL-6 levels were significantly higher in CAPD patients than in healthy controls, whereas both were higher in patients with LVH than in patients without LVH. FGF-23 was found to be positively associated with left ventricle mass index (LVMI) and serum phosphate. IL-6 level was positively associated with LVMI and negatively correlated with serum albumin and hemoglobin. Serum FGF-23 level was positively correlated with IL-6 level. CONCLUSION: FGF-23 and IL-6 are independent risk factors for LVH in CAPD patients and both collaborated in causing LVH in CAPD.

[Effect of cordyceps sinensis extract on Klotho expression and apoptosis in renal tubular epithelial cells induced by angiotensin II].

OBJECTIVE: To investigate the effect of cordyceps sinensis (CS) extract and losartan (Los) on the expression of Klotho (Kl), P53, P21, and apoptosis in renal tubular epithelial cell NRK-52E induced by angiotensin II (Ang II), and to elucidate its therapeutical mechanism in Ang II induced renal tubular epithelial cell apoptosis. METHODS: NRK-52E cells were incubated with CS with or without Ang II for 24 hours. Experimental groups were divided according to the increasing concentrations of CS:0 (serving as controls), 5, 10, 20, 40, and 80 mg/L. The optimal concentration of CS was selected and cells were divided into 5 groups: controls, Ang II (1*10(-8) mol/L), Ang II (1*10(-8) mol/L)+CS (40 mg/L), Ang II (1*10(-8) mol/L)+Los (1*10(-5) mol/L), and Ang II (1*10(-8) mol/L)+CS (40 mg/L)+Los (1*10(-5) mol/L). After 24 hours, cell proliferation was evaluated by MTT assay. The mRNA and protein expression of Kl, P53 and P21 were measured by RT-PCR. Activity of caspase-3 was evaluated by caspase-3 activity assay Kit. Cell apoptosis was determined by Annexin V-FITC/PI double staining and flow cytometry. RESULTS: Certain concentrations of CS promoted the proliferation of NRK-52E cells and increased cells proliferation inhibited by Ang II (P<0.01 or P<0.05 ). Ang II significantly down-regulated the mRNA and protein expression of Kl, and up-regulated the levels of P53 and P21. Caspase-3 activity and apoptotic rates were decreased, too (all P values<0.01). CS or/and Los significantly increased the expression of Kl mRNA and protein down-regulated by Ang II, decreased P53 mRNA and protein expression, P21 mRNA and protein expression,and inhibited caspase-3 activity and apoptotic rates(all P values<0.05). No cooperative effects were observed in the two drugs (P>0.05). CONCLUSION: CS can increase the expression of Kl down-regulated by Ang II, decrease P53 and P21 expression and caspase-3 activity, and reduce Ang II induced NRK-52E cell apoptosis, which may be part of its mechanism of the protective effects on hypertensive renal damage.