Assessment of selected angiogenesis markers in the serum of middle-aged male patients with plaque psoriasis.

Local angiogenesis accompanies inflammation in psoriasis-affected skin. To determine the serum concentrations of selected pro- and anti-angiogenic factors and their interrelationships in patients with plaque psoriasis. The study included 41 men diagnosed with psoriasis, aged 43.5 ± 11.7 years. The Psoriasis Area and Severity Index score was 23.4 ± 5.2 points. The control group consisted of 38 healthy, age-matched men. The levels of pro-angiogenic cytokines and angiogenesis inhibitors, including fibroblast growth factor 1 (FGF-1), vascular endothelial growth factor A (VEGF-A), endostatin, and angiostatin, were determined from the serum of patients and controls using enzyme-linked immunosorbent assays. Compared with controls, patients with psoriasis had a significantly lower concentration of FGF-1 (P = .01) but higher concentrations of endostatin (P = .04) and angiostatin (P = .02). The concentration of VEGF-A was also higher in patients with psoriasis but not significantly (P = .25). The concentration of C-reactive protein (CRP) was significantly higher among patients with psoriasis than controls (P < .0001). Among controls, CRP concentrations did not correlate significantly with the concentrations of FGF-1, VEGF-A, endostatin, or angiostatin. Among patients with psoriasis, CRP concentrations correlated moderately with the concentrations of VEGF-A (r = .35; P = .02) and angiostatin (r = .31; P = .04). The concentration of VEGF-A correlated positively with PASI (r = .05; P = .0009) and BSA values (r = .39; P = .01). Psoriasis is associated with an altered systemic balance between pro-angiogenic and anti-angiogenic factors. The increase in serum angiogenesis inhibitors may be associated with unfavorable changes in the development of coronary collateral circulation. However, the clinical significance of this has not yet been established.

Early VEGF testing in inflammatory neuropathy avoids POEMS syndrome misdiagnosis and associated costs.

BACKGROUND: Prompt diagnosis and early treatment prevents disability in Polyneuropathy Organomegaly Endocrinopathy Monoclonal-protein and Skin Changes (POEMS) syndrome. Delay in diagnosis is common with 55% of patients initially incorrectly diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients are often treated with intravenous immunoglobulin which is both expensive and ineffective in the treatment of POEMS. Testing patients with acquired demyelinating neuropathy with serum vascular endothelial growth factor (VEGF) more accurately identifies POEMS syndrome than the current standard of care. Incorporating VEGF testing into screening could prevent misdiagnosis and reduce costs. METHODS: We used observed treatment information for patients in the University College London Hospital's POEMS syndrome database (n=100) and from the National Immunoglobulin Database to estimate costs associated with incorrect CIDP diagnoses across our cohort. We conducted a model-based cost-effectiveness analysis to compare the current diagnostic algorithm with an alternative which includes VEGF testing for all patients with an acquired demyelinating neuropathy. RESULTS: Treatment associated with an incorrect CIDP diagnosis led to total wasted healthcare expenditures of between £808 550 and £1 111 756 across our cohort, with an average cost-per-POEMS-patient misdiagnosed of £14 701 to £20 214. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy would lead to annual cost-savings of £107 398 for the National Health Service and could prevent misdiagnosis in 16 cases per annum. CONCLUSIONS: Misdiagnosis in POEMS syndrome results in diagnostic delay, disease progression and significant healthcare costs. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy is a cost-effective strategy allowing for early POEMS diagnosis and potentially enabling prompt disease-directed therapy.

The Role of Angiogenesis Factors in the Formation of Vascular Changes in Scleroderma by Assessment of the Concentrations of VEGF and sVEGFR2 in Blood Serum and Tear Fluid.

Systemic sclerosis (SSc) is a connective tissue disorder characterized by tissue hypoxia, excessive fibrosis of skin and internal organs, and angiogenesis imbalance. The aim of the study was to evaluate in SSc patients the association between the retinal microcirculation disturbances and the presence of peripheral trophic changes and to determine the role of angiogenesis factors in the formation of vascular changes in scleroderma. Twenty-five SSc patients and 25 age- and sex-matched healthy controls were included to the study. Assay of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-2 (sVEGFR-2) in blood serum and tears was done for all patients and controls using enzyme-linked immunosorbent assay. Retinal blood circulation was investigated with fluorescein angiography (FA) in the SSc patients only. In our research, proportion of mainly hypertensive patients presenting with a large spectrum of retinal microvascular lesions was 72%, while proportion of patients with skin microvascular lesions within distal phalanxes of fingers and toes was 76%. We noticed that patients with pathological changes in the FA examination had finger ulcerations significantly more often than patients without changes in the eye fundus. There were no statistically significant differences in the serum concentration of VEGF and sVEGFR2 between subjects in both analyzed groups. Analysis of lower levels of VEGF (p = <0.001) and sVEGFR-2 (p = <0.001) in blood serum accompanied by simultaneous higher levels of VEGF/sVEGFR-2 ratio in tears of SSc patients, as compared with the control group, indicates the superiority of proangiogenic factors in patients' tears.

Impact of PAP therapy on hospitalization rates in Medicare beneficiaries with COPD and coexisting OSA.

OBJECTIVE: Growing evidence supports that patients with chronic obstructive pulmonary disease (COPD) and coexisting obstructive sleep apnea (OSA) have poor prognosis. This association is described as overlap syndrome. Positive airway pressure (PAP) therapy is now the preferred treatment for OSA. We hypothesized that use of PAP therapy in elderly patients with overlap syndrome would be associated with lower healthcare utilization. METHODS: In this retrospective cohort study, we analyzed data from 5% national sample of fee-for-service Medicare beneficiaries with a diagnosis of COPD who were newly started on PAP therapy in 2011. We examined the effect of PAP therapy on emergency room (ER) visits and hospitalizations for all-cause and COPD-related conditions in the 1 year pre- and 1 year post-initiation of PAP therapy. RESULTS: In year 2011, we identified 319 patients with overlap syndrome who were new users of PAP therapy. In this cohort of patients, hospitalization rates for COPD-related conditions were significantly lower in the 1 year post-initiation of PAP therapy compared to the 1-year pre-initiation period (19.4 vs 25.4%, P value = 0.03). However, ER visits (for any cause or COPD-related conditions) and hospitalization rates for any cause did not differ significantly in the pre- and post-initiation periods. PAP therapy was more beneficial in older adults, those with higher COPD complexity, and those with three or more comorbidities. CONCLUSION: Initiation of PAP therapy in elderly patients with overlap syndrome is associated with a reduction in hospitalization for COPD-related conditions, but not for all-cause hospitalizations and ER visits.

Serial Assessment of Growth Factors Associated with Liver Regeneration in Patients Operated with Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy.

BACKGROUND: There is limited knowledge about the mechanisms behind the unparalleled growth of the future liver remnant (FLR) linked to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). In this study, liver regenerative markers were examined in patients subjected to ALPPS. METHODS: Ten patients with colorectal liver metastases treated with neoadjuvant chemotherapy and ALPPS were included. Plasma was sampled at 6 time points and biopsies from both liver lobes were collected at both stages of ALPPS. The levels of interleukin (IL)-6, hepatocyte growth factor (HGF), tumor necrosis factor-α, epidermal growth factor, and vascular endothelial growth factor in plasma were measured at each time point. Expression of mRNA for markers of proliferation and apoptosis was studied in the biopsies from both liver lobes taken at both stages. RESULTS: ALPPS resulted in a peak of IL-6 after stage 1 (p = 0.004), which decreased rapidly and did not increase again after stage 2. HGF also increased after stage 1 (p = 0.048), and the HGF levels correlated significantly with the degree of growth of the FLR before stage 2 (p = 0.02, r2 = 0.47). There was a correlation between peak levels of IL-6 and HGF (p = 0.03, r2 = 0.84). CONCLUSIONS: IL-6 and HGF seem to be early mediators of hypertrophy after stage 1 in the ALPPS procedure. The peak HGF plasma level correlates with the degree of FLR growth in patients subjected to ALPPS.

Fibrogenic/Angiogenic Linker for Non-Invasive Assessment of Hepatic Fibrosis Staging in Chronic Hepatitis C Among Egyptian Patients.

Background and rationale for the study. Liver biopsy is the golden standard for staging liver fibrosis, but it may be accompanied by complications. Because of this complication, the aim of this study is to evaluate a simple noninvasive score to assess hepatic fibrosis in chronic hepatitis C genotype 4 patients which is very may have an important in diagnosis and therapeutic decision. This score [HA vascular (HAV) score] is a combination of direct markers [hyaluronic acid (HA) and vascular endothelial growth factor (VEGF)] and indirect markers [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR)]. RESULTS: Samples were collected from 220 patients (F0-F4): an estimated group (n = 120) and a validated group (n = 100). HA and VEGF levels, HCV RNA, liver function tests, platelet counts were assayed, Fibroscan was done and liver biopsy was taken and the stage of liver fibrosis and the grade of inflammatory activity was calculated according to Metavir score system. HA vascular (HAV) score = -35.1 + 0.14 (HA) (ng/L) + 0.03 (VEGF) (pg/mL) + (-6.7) [AAR (AST/ALT ratio)]. The HAV score produced areas under curve of 0.979 and 0.994 for significant (F2-F4) and advanced fibrosis (F3-F4) (cut off = 0.583 and 6.3, respectively). Surprisingly, the validation study of this score gave very good values of AUCs i.e. 0.990, 0.996 and 0.995 for significant, advanced and liver cirrhosis. CONCLUSIONS: Our developed score can not only help to assess liver fibrosis staging effectively but also avoid the invasiveness and the limitations of liver biopsy in Egyptian hepatitis C virus patients.

Highly sensitive antibody-aptamer sensor for vascular endothelial growth factor based on hybridization chain reaction and pH meter/indicator.

Vascular endothelial growth factor (VEGF) is a crucial signaling protein for the tumor growth and metastasis, which is also acted as the biomarkers for various diseases. In this research, we fabricate an aptamer-antibody sensor for point-of-care test of VEGF. Firstly, target VEGF is captured by antibody immobilized on the microplate, and then binds with aptamer to form the sandwich structure. Next, with the assist of glucose oxidase (GOx)-functionalized ssDNAs, hybridization chain reaction occurs using the aptamer as the primer. Thus, GOx are greatly gathered on the microplate, which catalyzes the oxidization of glucose, leading to the pH change. As a result, the detect limit at a signal-to-noise was estimated to be 0.5pg/mL of target by pH meter, and 1.6pg/mL of VEGF was able to be distinguished by naked eyes. Meanwhile, this method has been used assay VEGF in the serum with the satisfactory results.

Assessment of Serum Vascular Endothelial Growth Factor Levels in Pregnancy-Induced Hypertension Patients.

Objective. The objective of the study was to assess the serum vascular endothelial growth factor (VEGF) levels in peripheral blood of patients with pregnancy-induced hypertension (PIH) and find association between serum VEGF levels and PIH. Methods. Thirty-five PIH subjects, 35 normal pregnant females, and 20 normal healthy females were included in the study. Detailed history, clinical examination, and relevant biochemical parameters were assessed; serum VEGF levels were estimated using Double-antibody enzyme-linked immunosorbent assay. Results. The study groups were found to be age matched (p = 0.38). VEGF level in the pregnancy-induced hypertensive group (median = 109.19 (3.38 ± 619)) was significantly higher than the normal pregnant (median = 20.82 (1.7-619)) and control (median = 4.92 (1.13-13.07)) group and the difference between these three groups was significant (p < 0.0001). The 3 groups are found to be significantly different in terms of RBS (p = 0.01), urea (p < 0.0001), creatinine (p = 0.0005), AST (p = 0.0032), ALT (p = 0.0007), total protein (p = 0.0004), albumin (p < 0.0001), calcium (p = 0.001), and sodium (p = 0.02), while no statistically significant difference was found between total bilirubin (p = 0.167), direct bilirubin (p = 0.07), uric acid (p = 0.16), and potassium (p = 0.14). Conclusion. Significantly higher levels of serum VEGF were noted in PIH subjects compared to normal pregnant and control subjects.

[New assessment method in rheumatoid arthritis].

To assess disease activity in rheumatoid arthritis (RA), several composite measures have been used. However, more objective indices have been desired due to subjectivity in conventional indices. The Multi-Biomarker Disease Activity(MBDA) score is a novel serum testing based disease activity score ranging 1-100, derived from pre-specified algorithms in combination with 12 biomarkers. The MBDA score not only reflects disease activity in RA, but also is predictive for radiographic progression and risk of flare after drug reduction. Here we review usefulness of the MBDA score in RA.

Assessment of disease activity in rheumatoid arthritis by multi-biomarker disease activity (MBDA) score.

For assessing clinical disease activity in rheumatoid arthritis (RA), several composite measures of physical findings, patents'/evaluators' visual analog scales, and acute phase reactants has been used, contributing to advance in therapies through many clinical trials. However, more objective indices have been desired due to subjectivity in conventional indices. The Multi-Biomarker Disease Activity (MBDA) score is a novel blood-test based disease activity score of single integer ranging 1-100, derived from pre-specified algorithms in combination with 12 serum biomarkers (VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, YKL-40, MMP-1, MMP-3, leptin, resistin, SAA, CRP). The MBDA score not only reflects disease activity in RA, but also is predictive for radiographic progression and risk of flare after drug reduction. Herein we review clinical usefulness of the MBDA score in RA.

The assessment of the prognostic value of tumor markers and cytokines as SCCAg, CYFRA 21.1, IL-6, VEGF and sTNF receptors in patients with squamous cell cervical cancer, particularly with early stage of the disease.

The aim of this study is to determine the prognostic value of tumor markers, as squamous cell carcinoma antigen (SCCAg) and cytokeratin-19 fragment (CYFRA 21.1) and interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), soluble tumor necrosis factor receptor I (sTNF RI), and sTNF RII in patients with squamous cell carcinoma of the cervix. The subjects of analysis were 138 patients with stage I-IVA according to the International Federation of Gynecology and Obstetrics (FIGO) classification. The collected research material comes from one oncology center. During the 10 years of follow-up, 56 relapses and 53 deaths were observed, and recurrent disease in early stage was confirmed in 45 % of patients. The pretreatment serum levels of SCCAg and CYFRA 21.1, and cytokines IL-6, VEGF, sTNF RI, and sTNF RII were determined in all patients. The probability of disease-free survival (DFS) and overall survival (OS) was evaluated using the log-rank test and the Cox regression model. Based on the ROC curve analysis for patients with recurrence, the largest area under the curve was demonstrated for SCCAg and IL-6 and for patients who died, for SCCAg and VEGF. Cox analysis demonstrated that independent prognostic factor for DFS was only SCCAg and for OS cytokine IL-6 and SCCAg, but in patients with early stage the prognostic value for DFS was VEGF, whereas IL-6 and CYFRA 21.1 for OS. Serum level of VEGF, CYFRA 21.1 and IL-6 before treatment in patients with early stage cervical cancer appears to be an important prognostic factor.

Assessment of angiogenesis modulators in pregnant women with pre-eclampsia: a case-control study.

PURPOSE: This study aimed to evaluate the serum concentration of factors associated with placental angiogenesis in pre-eclamptic and normotensive pregnant women. METHODS: This was a prospective, cross-sectional, case-control study in which the pro-angiogenic factors PlGF, VEGF and IL-10, and the anti-angiogenic factors IL-6, IL-17 and TNF-α of 55 pregnant women (31 with pre-eclampsia-PE and 24 normotensive), with gestational age ≥20 weeks, were measured in maternal blood through the enzyme-linked immunosorbent assay (ELISA). The Mann-Whitney and Kruskal-Wallis tests were used for comparison between groups. RESULTS: Serum PIGF was reduced in the group of pregnant women with PE when compared with the normotensive women (493.2 ± 55.1 pg/mL vs. 4.4 ± 26.5 pg/mL; p < 0.001). There was no significant difference in PlGF levels in the pre-eclamptic pregnant women in relation to gestational age or proteinuria levels (p > 0.05). The serum levels of VEGF, IL-17, IL-10 and TNF-α were lower in the pregnant women with PE when compared with their normotensive peers, while the IL-6 levels were higher; however, this difference was not statistically significant (p > 0.05). CONCLUSION: Serum PlGF levels were reduced in the pregnant women with PE and were unrelated to disease severity. Serum levels of VEGF, IL-17, IL-10 and TNF-α were reduced in the pre-eclamptic pregnant women when compared with their normotensive peers, without statistically significant differences.

Assessment of follicular and serum VEGF and IGF-1 in ICSI patients: hMG vs rFSH.

PURPOSE: To investigate the effect of recombinant follicular stimulating hormone (r-FSH) and human menopausal gonadotropin (hMG) on follicular microenvironment via assessment of follicular and serum vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) levels in intracytoplasmic sperm injection (ICSI) cycles. MATERIALS AND METHODS: Designed as a prospective cohort study. Twenty-five patients underwent controlled ovarian hyperstimulation (COH) with r-FSH and 20 patients underwent with hMG. RESULTS: Both groups were comparable regarding the women's mean age and body mass index (BMI). The amount of VEGF (pg/ml) in serum and follicular fluid in the group I and II were comparable (275 ± 135.3 vs 330.7 ± 190.0; p > 0.05 and 2,081.1 ± 1095.1 vs 1,971.1 ± 975.6; p > 0.05, respectively). The amount of IGF-1 (ng/ml) in serum and follicular fluid in the group I and II were also comparable (225.3 ± 69.3 vs 204.1 ± 56.3, p > 0.05 and 176.1 ± 67.2 vs 185.8 ± 48.7, p > 0.05, respectively). Pregnancy rates were also comparable between groups. CONCLUSIONS: The hMG and r-FSH in COH produced comparable follicular microenvironment regarding follicular VEGF and IGF-l.

Early effects of liver regeneration on endocrine pancreas: in vivo change in islet morphology and in vitro assessment of systemic effects on ß-cell function and viability in the rat model of two-thirds hepatectomy.

Liver and pancreas share key roles in glucose homeostasis. Liver regeneration is associated with systemic modifications and depends especially on pancreatic hormones. The aim of the study was to investigate the role of systemic factors released after two-thirds hepatectomy (2/3H) on early possible consequences of liver regeneration on endocrine pancreas structure and function. The pancreas and serum were harvested 1, 2, or 3 days after 2/3H or sham operation in Lewis rats. The HGF and VEGF serum concentrations and plasma microparticles levels were measured. The fate of endocrine pancreas was examined through islets histomorphometry and function in sham and 2/3H rats. ß-Cell line RIN-m5F viability was assessed after 24 h of growth in media supplemented with 10% serum from 2/3H or sham rats instead of FCS. Three days after surgery, the pancreas was heavier in 2/3H compared to sham rats (0.56 vs. 0.40% of body weight, p < 0.05) and the proportion of islets of intermediate size was lower in 2/3H rats (5 vs. 15%, p < 0.05). Compared to Sham, sera obtained 3 days after hepatectomy were more efficient to maintain the viability of RIN-m5F cells (99 vs. 67%, p < 0.01). Three days after surgery, no significant differences in serum HGF, a trend to significant increase in VEGF concentration and a significant increase in microparticles levels, were observed in 2/3H vs. sham rats (9.8 vs. 6.5 nM Phtd Ser Eq., p < 0.05). Liver regeneration is associated with early effects on islets and could influence ß-cell viability and function by systemic effect.

Reparative therapy for acute ischemic stroke with allogeneic mesenchymal stem cells from adipose tissue: a safety assessment: a phase II randomized, double-blind, placebo-controlled, single-center, pilot clinical trial.

BACKGROUND: Few studies have evaluated the possible beneficial effect of the administration of stem cells in the early stages of stroke. Intravenous administration of allogeneic mesenchymal stem cells (MSCs) from adipose tissue in patients with acute stroke could be a safe therapy for promoting neurovascular unit repair, consequently supporting better functional recovery. We aim to assess the safety and efficacy of MSC administration and evaluate its potential as a treatment for cerebral protection and repair. MATERIALS: A Phase IIa, prospective, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Twenty patients presenting acute ischemic stroke will be randomized in a 1:1 proportion to treatment with allogeneic MSCs from adipose tissue or to placebo (or vehicle) administered as a single intravenous dose within the first 2 weeks after the onset of stroke symptoms. The patients will be followed up for 2 years. Primary outcomes for safety analysis: adverse events (AEs) and serious AEs; neurologic and systemic complications, and tumor development. Secondary outcomes for efficacy analysis: modified Rankin Scale; NIHSS; infarct size; and biochemical markers of brain repair (vascular endothelial growth factor, brain-derived neurotrophic factor, and matrix metalloproteinases 9). RESULTS AND CONCLUSIONS: To our knowledge, this is the first, phase II, pilot clinical trial to investigate the safety and efficacy of intravenous administration of allogeneic MSCs from adipose tissue within the first 2 weeks of stroke. In addition, its results will help us define the best criteria for a future phase III study.

Assessment of the differences in pharmacokinetics and pharmacodynamics between four distinct formulations of triamcinolone acetonide.

PURPOSE: To compare the durability of Kenalog, Trivaris, Triesence, and compounding pharmacy preservative-free triamcinolone acetonide in pigmented rabbits with syneretic vitreous using direct visualization, pharmacodynamics, and pharmacokinetics. METHODS: Twenty-five Dutch-belted rabbits were used. Pharmacokinetic experiment: Rabbits were intravitreally injected with one of four 4-mg triamcinolone acetonide formulations. Wide-field imaging was serially performed to document residual drug mass. Pharmacodynamics experiment: Four triamcinolone acetonide groups and one control group received intravitreal recombinant human vascular endothelial growth factor 165 every 2 weeks and were followed with fluorescein angiography to assess vascular endothelial growth factor retinal vasculopathy as a measure of residual steroid effect. Particle size of the formulations was measured with Mastersizer 2000. RESULTS: Remaining triamcinolone acetonide mass after 19 weeks: 12,091 ± 2,512 pixels for the Kenalog group, 1,307.36 ± 695.57 for Trivaris, 5577 ± 1477 for Triesence, and 1,535 ± 329 for compounded preservative-free triamcinolone acetonide. Kenalog suppressed recombinant human vascular endothelial growth factor-induced retinopathy more effectively than the other triamcinolone acetonide groups at Week 39, the final time point assessed. Particle size (90th percentile) was 47 µm for Kenalog, 26 µm for Triesence, and 22 µm for both compounded preservative-free triamcinolone acetonide and Trivaris. CONCLUSION: Triamcinolone acetonide formulations do not have the same pharmacokinetics/pharmacodynamics. Kenalog has the longest vitreous visibility and durability. Particle size appears to correlate with efficacy and durability.

Serum vascular adhesion protein-1 correlates with vascular endothelial growth factor in patients with type II diabetes.

AIMS: To study serum levels of soluble vascular adhesion protein (sVAP)-1 in type II diabetic patients with retinopathy. METHODS: Serum samples were obtained from 53 consecutive patients, including 14 cases with non-angiogenic ocular diseases, i.e., epiretinal membrane (ERM) and idiopathic macular hole (MH), 19 cases with age-related macular degeneration (AMD), and 20 cases with diabetic retinopathy (DR). Protein levels of sVAP-1, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay. Enzymatic activity of semicarbazide-sensitive amine oxidase (SSAO) was also measured. RESULTS: Serum level of sVAP-1 showed a moderate correlation with SSAO activity in all cases. Patients with DR had higher levels of serum sVAP-1 than subjects with ERM and MH, or those with AMD; however, severity of DR is not related to the serum levels of sVAP-1. Serum sVAP-1 correlated positively with VEGF in patients with DR, but not in those with ERM and MH, or those with AMD. Neither soluble ICAM-1 nor VCAM-1 correlated with VEGF, even in subjects with DR. CONCLUSION: The current data demonstrate the elevated serum levels of sVAP-1 and correlation between sVAP-1 and VEGF in patients with type II diabetes.

Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN randomized trial.

PURPOSE: To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD). DESIGN: Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560). PARTICIPANTS: People >50 years of age with untreated nAMD in the study eye who read ≥ 25 letters on the Early Treatment Diabetic Retinopathy Study chart. METHODS: We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review. MAIN OUTCOME MEASURES: The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs. RESULTS: Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P<0.0001) and higher with discontinuous treatment (GMR, 1.23; 95% CI, 1.07 to 1.42; P = 0.004). Continuous and discontinuous treatment costs were £9656 and £6398 per patient per year for ranibizumab and £1654 and £1509 for bevacizumab; bevacizumab was less costly for both treatment regimens (P<0.0001). CONCLUSIONS: The comparison of visual acuity at 1 year between bevacizumab and ranibizumab was inconclusive. Visual acuities with continuous and discontinuous treatment were equivalent. Other outcomes are consistent with the drugs and treatment regimens having similar efficacy and safety. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references.

Assessment of levels of vascular endothelial growth factor in patients with ESRD and its possible role in cardiovascular morbidity and mortality.

Patients with end-stage renal disease (ESRD) are known to have an elevation of a variety of abnormal thrombotic and inflammatory markers associated with high cardiovascular mortality. Vascular endothelial growth factor (VEGF) is also dysregulated in ESRD but not much is known about the serum levels of VEGF in patients with ESRD. Published reports suggest that elevated levels of VEGF may be protective to the kidney during periods of acute injury and may maintain local glomerular function. Impaired production of VEGF may lead to proteinuria, hypertension, and thrombotic microangiopathy. However, its role in chronic kidney disease or ESRD remains undefined. In our study, we analyzed blood samples of 52 patients with ESRD on stable hemodialysis regimen and measured predialysis serum levels of VEGF and compared these with blood samples obtained from 50 healthy volunteers in order to study differences between baseline levels of VEGF and also attempted to determine its role in ESRD-related cardiovascular mortality.

Assessment of serum vascular endothelial growth factor and nail fold capillaroscopy changes in systemic lupus erythematosus with and without cutaneous manifestations.

Angiogenesis and microvascular endothelial injury play a role in the pathogenesis of systemic lupus erythematosus (SLE). Vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, and nail fold capillaroscopy (NFC) have been investigated in few studies in SLE with no reports targeting SLE with cutaneous manifestations. To evaluate NFC changes and VEGF serum level in relation to disease activity in SLE patients with versus without cutaneous manifestations. Thirty SLE patients (15 with cutaneous manifestations [group I], 15 without [group II]) and 15 healthy controls were evaluated for VEGF serum levels, NFC changes and were related to disease activity. VEGF serum levels were significantly higher in patients than controls (median and interquartile range [IQR]: 2110.77, 471.09-4714.30 vs. 60.00, 14-366, respectively, P < 0.0001). VEGF cut-off value to predict SLE patients was more than 293 and to detect moderate and severe SLE activity was more than 422 pg/mL and more than 3800 pg/mL, respectively. Serum VEGF levels increased with increased disease activity (P < 0.05). It was significantly higher in group I than group II (median and IQR: 2624.74, 1801.39-4141.70 vs. 862.50, 180-2426.95, respectively, P < 0.05). Mean serum VEGF was significantly higher with NFC score 3 than 1 (P = 0.008). NFC score and SLE activity were significantly associated in patients (P < 0.05). Serum VEGF is significantly elevated in SLE patients with cutaneous manifestations and its cut-off values to detect different activity grades of SLE are identified. Abnormalities in NFC reflect the extent of microvascular involvement in SLE.