Intravitreal anti-VEGF agents, oral glucocorticoids, and laser photocoagulation combination therapy for macular edema secondary to retinal vein occlusion: preliminary report

AIM： To evaluate the efficacy and safety of combined anti-vascular endothelial growth factor （VEGF） agents, oral glucocorticoid, and laser photocoagulation therapy for macular edema （ME） secondary to retinal vein occlusion （RVO）. METHODS： This study included 16 eyes of 16 patients with RVO-associated ME. Patients were initially treated with oral prednisone and an intravitreal anti-VEGF agent. Two weeks later, patients underwent standard laser photocoagulation. Best-corrected visual acuity （BCVA）, central retinal thickness （CRT）, and retinal vessel oxygenation were examined over 12mo. RESULTS： Patients received 1.43＋0.81 anti-VEGF injections. Mean baseline and 12-month IogMAR BCVA were 0.96±0.51 （20/178） and 0.31±0.88 （20/40）, respectively, in eyes with central retinal vein occlusion （CRVO） （P〈0.00）, and 1.02±0.45 （201209） and 0.60±0.49 （20/80）, respectively, in eyes with branch retinal vein occlusion （BRVO） （P〈0.00）. At 12mo, CRT had significantly decreased in eyes with CRVO （P〈0.00） and BRVO （P〈0.00）. Venous oxygen saturation had significantly increased in eyes with CRVO （P〈0.00） and BRVO （P〈0.00）. No examined parameters were significantly different between the 2 RVO groups. No serious adverse effects occurred. CONCLUSION： Anti-VEGF, glucocorticoid, and photocoagulation combination therapy improves visual outcome, prolongs therapeutic effect, and reduces the number of intravitreal injections in eyes with RVO- associated ME.

Efficacy and safety of anti-vascular endothelial growth factor agents on corneal neovascularization: A meta-analysis

BACKGROUND Corneal neovascularization(CoNV)is the second major cause of blindness.Vascular endothelial growth factor(VEGF)inhibitors,e.g.,bevacizumab,have been used to prevent CoNV.AIM We conducted an updated systematic review and meta-analysis of clinical trials to examine the efficacy and safety of anti-VEGF in CoNV.METHODS A literature search was conducted using three electronic databases.Mean difference(MD),standard mean difference(SMD),and relative risk(RR)are used to estimate the effect size.RESULTS Nine randomized controlled and three non-randomized trials were obtained.The pooled results demonstrated a significant reduction of CoNV area/Length(SMD=-1.17,95%CI:-1.58 to-0.75),best corrected visual acuity(MD=-0.54,95%CI:-0.91 to-0.17),and graft rejection(RR=0.44,95%CI:0.24 to 0.8)and failure(RR=0.39,95%CI:0.19 to 0.78)rates in the anti-VEGF group than the placebo group.A non-significant reduction of the epithelial defect was also observed in the bevacizumab group compared with the placebo(RR=0.56,95%CI:0.30 to 1.06).Compared with a placebo,the unsynthesizable trials also support that bevacizumab improves visual acuity,CoNV,graft rejection,and failure rates.Trials reporting other comparisons revealed the superiority of combined remedy with bevacizumab compared to other treatments in reducing CoNV.CONCLUSION Anti-VEGF agents,mainly bevacizumab,are an effective and safe treatment for CoNV of all causes and prevent corneal graft rejection and failure in corneal transplantation.

What is new in the pathogenesis and treatment of IgA glomerulonephritis

Recently,new findings have been clarified concerning both pathogenesis and treatment of IgA nephritis.The four hits theory has been confirmed but several genetic wide association studies have allowed finding several genes connected with the pathogenesis of the disease.All these new genes apply to each of the four hits.Additionally,new discoveries concerning the microbiota and its connection with immune system and IgA generation have allowed finding out the role of the mucosa in IgA nephropathy pathogenesis.The IgA treatment is also changed included the future possibilities.The treatment of the chronic kidney disease,associated with the nephropathy,is mandatory,since the beginning of the disease.The classical immunosuppressive agents have poor effect.The corticosteroids remain an important cornerstone in any phase of the disease.More effect is related to the treatment of B cells and plasma cells.In particular,in very recent studies have been documented the efficacy of anti B cell-activating factor and anti A proliferation-inducing ligand agents.Most of these studies are to date in phase II/III.Finally,new agents targeting complement are arising.These agents also are still in randomized trials and act principally in hit 4 where the immunocomplexes in the mesangium activate the different pathways of the complement cascade.

Preventing infective complications in inflammatory bowel disease

Over the past decade there has been a dramatic change in the treatment of patients with Crohn’s disease and ulcerative colitis, which comprise the inflammatory bowel diseases (IBD). This is due to the increasing use of immunosuppressives and in particular the biological agents, which are being used earlier in the course of disease, and for longer durations, as these therapies result in better clinical outcomes for patients. This, however, has the potential to increase the risk of opportunistic and serious infections in these patients, most of which are preventable. Much like the risk for potential malignancy resulting from the use of these therapies long-term, a balance needs to be struck between medication use to control the disease with minimization of the risk of an opportunistic infection. This outcome is achieved by the physician’s tailored use of justified therapies, and the patients’ education and actions to minimize infection risk. The purpose of this review is to explore the evidence and guidelines available to all physicians managing patients with IBD using immunomodulating agents and to aid in the prevention of opportunistic infections.

Adalimumab in prevention of postoperative recurrence of Crohn's disease in high-risk patients

AIM:To evaluate the effectiveness of adalimumab in preventing recurrence after intestinal resection for Crohn's disease in high-risk patients.METHODS:A multicenter,prospective,observational study was conducted from June 2009 until June 2010.We consecutively included high-risk Crohn's disease patients who had undergone an ileal/ileocolonic resection.High-risk patients were defined as two or more criteria:smokers,penetrating pattern,one or more previous surgical resections or prior extensive resection.Subcutaneous adalimumab was administered 2 wk(± 5 d) after surgery at a dose of 40 mg eow,with an initial induction dose of 160/80 mg at weeks 0 and 2.Demographic data,previous and concomitant treatments(antibiotics,5-aminosalicylates,corticosteroids,immunomodulators or biologic therapies),smoking status at the time of diagnosis and after the index operation and number of previous resections(type and reason for surgery) were all recorded.Biological status was assessed with C-reactive protein,erythrocyte sedimentation rate and fecal calprotectin.One year(± 3 mo) after surgery,an ileocolonoscopy and/or magnetic resonance enterography was performed.Endoscopic recurrence was defined as Rutgeerts score ≥ i2.Morphological recurrence was based on magnetic resonance(MR) score ≥ MR1.RESULTS:Twenty-nine patients(55.2% males,48.3% smokers at diagnosis and 13.8% after the index operation),mean age 42.3 years and mean duration of the disease 13.8 years were included in the study.A mean of 1.76(range:1-4) resections previous to adalimumab administration and in 37.9% was considered extensive resection.51.7% had previously received infliximab.Immunomodulators were given concomitantly to 17.2% of patients.Four of the 29(13.7%) developed clinical recurrence,6/29(20.7%) endoscopic recurrence and 7/19(36.8%) morphological recurrence after 1-year.All patients with clinical recurrence showed endoscopic and morphological recurrence.A high degree of concordance was found between clinical-endoscopic recurrence(k = 0.76,P < 0.001) and clinical-morphological recurrence(k = 0.63,P = 0.003).Correlation between endoscopic and radiological findings was good(comparing the 5-point Rutgeerts score with the 4-point MR score,a score of i4 was classified as MR3,i3 as MR2,and i2-i1 as MR1)(P < 0.001,r s = 0.825).During follow-up,five(17.2%) patients needed adalimumab dose intensification(40 mg/wk);Mean time to intensification after the introduction of adalimumab treatment was 8 mo(range:5 to 11 mo).In three cases(10.3%),a biological change was needed due to a worsening of the disease after the dose intensification to 40 mg/wk.One patient suffered an adverse event.CONCLUSION:Adalimumab seems to be effective and safe in preventing postoperative recurrence in a selected group of patients who had undergone an intestinal resection for their CD.

Surgery for Crohn's disease in the era of biologicals:A reduced need or delayed verdict?

Crohn's disease(CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract.Ultimately,up to 70% of all patients will need surgery,despite optimized medical therapy.Moreover,about half of the patients will need redo-surgery because of disease recurrence.The introduction of anti-tumor necrosis factor(TNF) drugs(Infliximab in 1998) revolutionized the treatment of CD.Different randomized trials assessed the efficacy of anti-TNF treatment not only to induce,but also to maintain,steroid-free remission.Furthermore,these agents can rapidly lead to mucosal healing.This aspect is important,as it is a major predictor for long-term disease control.Subgroup analyses of responding patients seemed to suggest a reduction in the need for surgery at median-term follow up(1-3 years).However if one looks at population surveys,one does not observe any decline in the need for surgery since the introduction of Infliximab in 1998.The short follow-up term and the exclusion of patients with imminent surgical need in the randomized trials could bias the results.Only 60% of patients respond to induction of anti-TNF therapy,moreover,some patients will actually develop resistance to biologicals.Many patients are diagnosed when stenosing disease has already occurred,obviating the need for biological therapy.In a further attempt to change the actual course of the disease,top down strategies have been progressively implemented.Whether this will indeed obviate surgery for a substantial group of patients remains unclear.For the time being,surgery will still play a pivotal role in the treatment of CD.

What is left when anti-tumour necrosis factor therapy in inflammatory bowel diseases fails?

The inflammatory bowel diseases (IBDs) are chronic incurable conditions that primarily present in young patients. Being incurable, the IBDs may be part of the patient&#x02019;s life for many years and these conditions require therapies that will be effective over the long-term. Surgery in Crohn&#x02019;s disease does not cure the disease with endoscopic recurrent in up to 70% of patients 1 year post resection. This means that, the patient will require many years of medications and the goal of the treating physician is to induce and maintain long-term remission without side effects. The development of the anti-tumour necrosis factor alpha (TNF&#x003b1;) agents has been a magnificent clinical advance in IBD, but they are not always effective, with loss of response overtime and, at times, discontinuation is required secondary to side effects. So what options are available if of the anti-TNF&#x003b1; agents can no longer be used? This review aims to provide other options for the physician, to remind them of the older established medications like azathioprine/6-mercaptopurine and methotrexate, the less established medications like mycophenolate mofetil and tacrolimus as well as newer therapeutic options like the anti-integins, which block the trafficking of leukocytes into the intestinal mucosa. The location of the intestinal inflammation must also be considered, as topical therapeutic agents may also be worthwhile to consider in the long-term management of the more challenging IBD patient. The more options that are available the more likely the patient will be able to have tailored therapy to treat their disease and a better long-term outcome.

Acute renal artery occlusion following infliximab infusion

We report the case of a 44-year-old male patient who presented with acute renal artery occlusion, 3 d after frst injection of infiximab for steroid refractory attack of ulcerative colitis. Extensive work-up provided no evidence of predisposing factors for arterial thrombosis. Infiximab was thus suspected in the genesis of throm-bosis, based on both intrinsic and extrinsic criteria. At month 3 after thrombosis with ongoing anticoagulation, angio-tomodensitometry showed complete revascularization of the left renal artery with renal atrophy. Renal function remained normal and the patient was still in steroid free remission on mercaptopurin monotherapy at maximal follow-up. Few thromboembolic events have been described with anti- tumor necrosis factor （TNF） agents, but it is the frst case reported of renal artery thrombosis after infiximab infusion. In addition, we re-view thrombosis associated with anti-TNF agents.

Effect of calycosin on left ventricular ejection fraction and angiogenesis in rat models with myocardial infarction

OBJECTIVE:To evaluated the effect of calycosin on left ventricular ejection fraction and angiogenesis.METHODS:Adult male Sprague-Dawley rats were randomly assigned into calycosin-treated groups(0.5,1,2,and 4 mg/kg qd),a dimethyl sulfoxide(DMSO),or a sham-operated control group.The myocardial ischaemia(Ml) model was intraperitoneally administered calycosin for 28 days.The survival rates and left ventricular ejection fractions(LVEF)were compared between groups.The expression levels of vascular endothelial growth factor(VEGF)and cluster of differentiation 31(CD31) in ischaemic myocardium were also measured and compared.RESULTS:The construction of MI model resulted in a LVEF reduction of 50% compared with the sham-control.After 28 days,the LVEF value was 10% higher when calycosin(4 mg/kg) was administered compared with the DMSO group.The expression of VEGF and CD31 showed a dose-dependent manner when calycosin was administrated.The calycosin-treated(4 mg/kg) group displayed a twofold increase in VEGF expression at both the mRNA and protein levels compared with the DMSO group.In addition,CD31 expression in the microvascular increased 1.5-fold in the 4 mg/kg calycosin-treated group.CONCLUSION:Calycosin improved left ventricular ejection fraction in the MI rat models,induced VEGF expression in the ischaemic myocardium,increased CD31 expression and promoted angiogenesis.

Ethanol based foamed asphalt as potential alternative for low emission asphalt technology

Foamed asphalt typically relies on water as a foaming agent because water becomes gaseous at elevated temperatures, generating numerous tiny bubbles in the asphalt and causing spontaneous foaming. In this study, ethanol was used as a potential alternative to water as a foaming agent. Ethanol is expected to be a physical blowing agent in the same manner as water, except it requires less energy to foam due to its 78 ℃ boiling point. This study compares the performance of water and ethanol as foaming agents through the measurements of rotational viscosity, the reduction in temperature during foaming, and volatile loss. The ethanol-foamed asphalt binders were prepared at 80 ~C and 100 ~C, while the water-foamed asphalt binders were prepared at 100 ~C and 120 ~＇C. Additionally, the rolling thin film oven （RTFO） was used to generate short-term aging of the foamed asphalt binders. A rotational viscometer was used to determine the viscosity of the asphalt binders at 80 ~C, 100 ~C, 120 ~C, 140 ~C, and 160 ~C. Overall, ethanol can function in the same manner as water but requires less energy to foam. It is proven based on the smaller drop in temperature of the asphalt binder foamed using ethanol compared with that prepared with water. This is due to the lower latent heat capacity of ethanol, which requires less energy to vaporize compared with water. Through the rotational viscometer test, ethanol performs better in lowering the viscosity of asphalt binders, which is essential in allowing produc- tion processes at low temperatures, as well as a better workability and aggregate coating. Ethanol can be expelled from the foamed asphalt binders at a higher rate due to its lower boiling point and latent heat.

Vedolizumab in the treatment of Crohn’s disease of the pouch

Background:Our recent study showed the efficacy and safety of vedolizumab in the treatment of chronic antibioticrefractory pouchitis.However,there are no published studies on its efficacy and safety in Crohn’s disease(CD)of the pouch.The aim of this study was to assess the efficacy and safety of vedolizumab in those patients.Methods:This case series included all eligible patients with CD of the pouch from our prospectivelymaintained,IRB-approved Pouchitis Registry from 2015 to 2017.Disease activity in pouch patients can bemonitored using the modified Pouchitis Disease Activity Index(mPDAI).mPDAI is the 18-point pouchitis disease activity index consisting of three principal component scores:symptom(range,0–6 points),endoscopy,(range 0–6 points),and histology(range,2–6 points).Pre-and post-treatment(minimum 6 months)pouchoscopy and clinical visits were used to calculate mPDAI.Results:A total of 12 patients were included in this study,who had restorative proctocolectomy with ileal pouch anal anastomosis for medically refractory ulcerative colitis(UC).The mean age at the time of pre-colectomy diagnosis of UC was 25.0611.5 years.The mean current age was 41.0612.1 years,nine(75.0%)were female,three(25.0%)had smoked and eight(66.7%)had used anti-tumor necrosis factor agents prior to vedolizumab use.The mean duration of vedolizumab use was 1.066.4 years.There was a significant reduction in mPDAI symptom subscores after vedolizumab therapy(3.5061.93 vs 5.0860.79,P=0.015).The pre-and post-treatment mean endoscopy subscores were 1.2561.36 and 0.9161.50 in the afferent limb(P=0.583);2.5861.68 and 2.2762.05(P=0.701)in the pouch body;and 2.6761.93 and 2.0962.12(P=0.511)in the cuff,respectively.None of the patients experienced side effects throughout the vedolizumab therapy.Conclusion:The findings of our study suggests that vedolizumab appears to be effective and safe in reducing the symptoms in patients with CD of the pouch.