One year study of efficacy and safety of infliximab in the treatment of patients with ocular and neurological Behçet's disease refractory to standard immunosuppressive drugs

Abstract The aim of the study was to assess the long-term efficacy and safety of Infliximab therapy in the treatment of patients with Behçet’s disease refractory to standard immunosuppressive agents. Twenty-one patients that did not respond to corticosteroids and to at least one immunosuppressant (cyclosporin, methotrexate, azathioprine, cyclophosphamide) for the presence of ocular and/or CNS involvement were enrolled. Eighteen patients completed the study up to 54 weeks. Stable doses of prednisone (<10 mg/day) were permitted, immunosuppressants were discontinued at least 4 weeks prior baseline visit. The patients received three infusions of 5 mg/kg Infliximab (at weeks 0, 2 and 6) and then infusions of 5 mg/kg Infliximab every 8 weeks. At each visit data on clinical symptoms, response to therapy and adverse events were collected. The primary outcome of interest was to assess the clinical efficacy (total or partial recovery) of infliximab. Secondary end points were to evaluate quality of life and to monitor the safety of the drug. Eighteen patients achieved a total remission. Two patients achieved a partial remission and relapsed after 3 months from discontinuation of therapy. Infliximab was well tolerated throughout the study. A case of non-Hodgkin lymphoma was observed within 6 months. Minor side effects were headache, dizziness, tachycardia that regressed spontaneously and did not entail interruption. Anti-nuclear antibodies were not detected during the period of observation

Polypoidal choroidal vasculopathy in pachychoroid: combined treatment with photodynamic therapy and aflibercept

Introduction: To evaluate the effects of combined therapy using intravitreal Aflibercept (IVA) and photodynamic therapy (PDT) on polypoidal choroidal vasculopathy related to pachychoroid disease (PPCV). Methods: Patients with PPCV were treated with PDT combined with 3 IVA injections on a monthly basis, followed by pro re nata criteria. The 12-month follow-up consisted of multiple revaluations of visual acuity and SS-OCT parameters of clinical activity. Results: Nineteen eyes were included in the study; mean age was 65.5&nbsp;years. Visual acuity improved after 12&nbsp;months (0.35 ± 0.25 to 0.2 ± 0.20 logMAR, p = 0.005). Percentage of eyes with intraretinal and subretinal fluid reduced from baseline to the 12-month follow-up (from 52.6 to 10.5%, p = 0.12, and from 89.5 to 5.3% p = 0.0009, respectively). Central retinal and mean macular thicknesses reduced (258 ± 39.6 to 204.8 ± 38.8&nbsp;μm p = 0.04 and 293.8 ± 32.1 to 248.1 ± 29.6&nbsp;μm p = 0.017, respectively). Central choroidal and mean choroidal thicknesses also displayed a reduction (328.6 ± 54.9 to 289.8 ± 44.6&nbsp;μm p = 0.001 and 314.5 ± 55.3 to 287.9 ± 47.6&nbsp;μm p = 0.015, respectively). The mean number of injections was 4.6/year. Conclusion: The results support the use of a combined therapy with Aflibercept and PDT in PPCV. This treatment would act in synergy, with anti-VEGF controlling exudation and PDT closing the aneurysmal vessel and reducing choroidal congestion

Aquafeed production from fermented fish waste and lemon peel

In order to obtain a high-protein-content supplement for aquaculture feeds, rich in healthy microorganisms, in this study, Saccharomyces cerevisiae American Type Culture Collection (ATCC) 4126 and Lactobacillus reuteri ATCC 53608 strains were used as starters for fermenting fish waste supplemented with lemon peel as a prebiotic source and filler. Fermentation tests were carried out for 120 h until no further growth of the selected microorganisms was observed and the pH value became stable. All the samples were tested for proteins, crude lipids, and ash determination, and submitted for fatty acid analysis. Moreover, microbiological analyses for coliform bacteria identification were carried out. At the end of the fermentation period, the substrate reached a concentration in protein and in crude lipids of 48.55 ± 1.15% and 15.25 ± 0.80%, respectively, representing adequate levels for the resulting aquafeed, whereas the ash percentage was 0.66 ± 0.03. The main fatty acids detected were palmitic, oleic, and linoleic acids. Saturated fatty acids concentration was not affected by the fermentation process, whereas monounsaturated and polyunsaturated ones showed an opposite trend, increasing and decreasing, respectively, during the process. Coliform bacteria were not detected in the media at the end of the fermentation, whereas the amount of S. cerevisiae and L. reuteri were around 1011 and 1012 cells per g, respectively

Theory of Slow Light Enhanced Four-Wave Mixing in Photonic Crystal Waveguides

The equations for Four-Wave-Mixing in a Photonic Crystal waveguide are derived accurately. The dispersive nature of slow-light enhancement, the impact of Bloch mode reshaping in the nonlinear overlap integrals and the tensor nature of the third order polarization are therefore taken into account. Numerical calculations reveal substantial differences with simpler models, which increase with decreasing group velocity. We predict that the gain for a 1.3 mm long, unoptimized GaInP waveguide will exceed 10 dB if the pump power exceeds 1 W.Comment: 6 pages, 4 figures; submitted to Optics Expres

Short and middle term effects of hypocaloric low carbohydrate diet vs hypocaloric Mediterranean diet on endothelial function in obese subjects

Adequate nutritional treatment is required to address the problem of increasing prevalence of obesity in Western countries. The Mediterranean diet style is now acknowledged to have large scientific evidences in terms of cardiovascular prevention. However, many popular diets are diffusing also as self-prescribed treatments. Among those, the efficacy of low-carbohydrate diets (also known as Atkins’ diet in its most popular variety) has been addressed by some investigations. It is generally concluded that the low-carbohydrate diet is able to induce a greater weight loss, at least in the middle term, and a better serum lipid profile than the conventional diet. In this longitudinal, randomised, open study we compared the effects on endothelial function of a hypocaloric low-carbohydrate diet (according to the Atkins’ diet; AD) versus a similarly hypocaloric Mediterranean diet (MD). Overweight-obese (range of BMI: 27-34.9 Kg/m2; range of age: 30-50 years) otherwise healthy, normal glucose tolerant women were enrolled and randomly assigned to one of the two dietary treatments until reaching the final number of 10 women for each group of treatment. So, twenty-five women were enrolled and five of them (3 in the MD group and 2 in the AD group) were subsequently excluded from the study due to intercurrent diseases (1 subject) or declaration of inadequate compliance (2 subjects) or f voluntary drop out (2 subjects). Measurements were performed before (T0), 5-7 days (T5) and 2 months (T60) after starting the diet treatment. Endothelial function was investigated at each time of the study by measuring the brachial artery flow-mediated dilation (FMD). Serum concentrations of insulin, adiponectin, interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and 8-iso-prostaglandin (8-iso-PG) F2α were also assessed at each time of the study. Urinary ketone bodies were observed at T5 only in AD group. Briefly, body weight was not significantly decreased at T5 in both groups; as expected, a higher body weight reduction was observed at T60 in AD group (change in body weight T60 – T0, mean ± sem, MD -4.9 ± 0.6 Kg vs AD -7.6 ± 0.8 Kg, p= 0.014). The FMD was significantly reduced at T5 in the AD group and increased at T60 until reaching the T0 values (T0: 12.2 ± 2.9; T5: 5.2 ± 0.8; T60: 11.0 ± 1.2 %; p< 0.05 T5 vs T0 and T60). On the contrary, the FMD increased significantly at T5 in the MD group and decreased until reaching values comparable to those of T0 at T60 (T0: 10.3 ± 2.3; T5: 14.5 ± 2.8; T60: 10.6 ± 1.9 %; p< 0.05 T5 vs T0 and T60). This trend of FMD change was observed in each subject. Insulin concentrations and HOMA-I decreased significantly at T5 and at T60 in both groups. Adiponectin and TNF-α concentrations remained unchanged in both groups throughout the study. Both IL-6 and 8-iso-PGF2α increased significantly at T5 in the AD group and decreased at T60 to values comparable to T0 (IL-6: T0 57.5 ± 9.0, T5 78.1 ± 10.9, T60 56.6 ± 6.8 pg/ml; T5 vs T0 p< 0,005, T5 vs T60 p< 0,02; 8-iso-PGF2α: T0 171.5 ± 30.6, T5 222.6 ± 35.1, T60 178.7 ± 25.8 pg/ml; T5 vs T0 p< 0,005, T5 vs T60 p< 0,02); no significant change was observed in the MD group. This study suggests that the hypocaloric low-carbohydrate diet induces a significant endothelial dysfunction in the short term (5-7 days) that is reverted in the middle term (2 months) as suggested by both the brachial artery FMD and serum markers of inflammation (IL-6) and oxidative stress (8-iso-PGF2α). On the contrary, the hypocaloric Mediterranean diet is able to improve the endothelial function at least in the short term. These effects are independent of body weight loss. Therefore, this study points out also the potential disadvantages of low-carbohydrate diets when prescribed (or self-prescribed) especially in subjects at high cardiovascular risk

Relationship between albumin excretion rate and aortic stiffness in untreated essential hypertensive patients

OBJECTIVES: To evaluate, in a group of nondiabetic essential hypertensive patients with normal renal function, the relationship between albumin excretion rate (AER) and carotid-femoral pulse wave velocity (PWV), as an index of aortic stiffness. DESIGN: Cross-sectional study. SETTING: Outpatient hypertension clinic. SUBJECTS: Seventy patients with mild-to-moderate essential hypertension, aged 42 +/- 8 years, never pharmacologically treated. All subjects underwent routine laboratory tests, 24-h ambulatory blood pressure (BP) monitoring, measurement of carotid-femoral PWV, by means of a computerized method, and AER. RESULTS: Microalbuminuric patients (AER > or = 20 microg min(-1); n = 19), when compared with normoalbuminuric subjects, showed more elevated 24-h BP (136/88 +/- 10/10 vs. 128/83 +/- 7/6 mmHg; P < 0.001 and P = 0.013, for systolic and diastolic BP respectively) and higher values of carotid-femoral PWV (10.4 +/- 2 m s(-1) vs. 9.2 +/- 1.3; P = 0.006). This latter difference remained statistically significant, even after correction by ancova for 24-h systolic and diastolic BP, and body mass index (BMI, P = 0.016). Univariate regression analysis disclosed a tight correlation between AER and carotid-femoral PWV (r = 0.42; P = 0.0003). This association was confirmed in a multiple regression model (beta = 0.35; P = 0.009) in which, as independent variables, besides PWV, 24-h BP, age, serum glucose values, smoking status, gender and BMI, were added. CONCLUSIONS: Our results seem to confirm that microalbuminuria may represent the early renal manifestation of a widespread vascular dysfunction, and therefore it is an integrated marker of cardiovascular risk

Screening and Management of Coronary Artery Disease in Kidney Transplant Candidates

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD), especially in end-stage renal disease (ESRD) patients and during the first year after transplantation. For these reasons, and due to the shortage of organs available for transplant, it is of utmost importance to identify patients with a good life expectancy after transplant and minimize the transplant peri-operative risk. Various conditions, such as severe pulmonary diseases, recent myocardial infarction or stroke, and severe aorto-iliac atherosclerosis, need to be ruled out before adding a patient to the transplant waiting list. The effectiveness of systematic coronary artery disease (CAD) treatment before kidney transplant is still debated, and there is no universal screening protocol, not to mention that a nontailored screening could lead to unnecessary invasive procedures and delay or exclude some patients from transplantation. Despite the different clinical guidelines on CAD screening in kidney transplant candidates that exist, up to today, there is no worldwide universal protocol. This review summarizes the key points of cardiovascular risk assessment in renal transplant candidates and faces the role of noninvasive cardiovascular imaging tools and the impact of coronary revascularization versus best medical therapy before kidney transplant on a patient’s cardiovascular outcome

Relationship of choroidal thickness with pulsatile hemodynamics in essential hypertensive patients

Controversy exists about the association of choroidal thickness (CTh) with blood pressure (BP) values. There is some evidence suggesting that central hemodynamics changes are associated with microvascular disease. Our study was aimed to assess the relationships between CTh and clinic and 24-h BP and between CTh and estimated 24-h aortic pulse pressure (aPP), 24-h aortic systolic BP (aSBP), and 24-h aortic augmentation index (aAIx) in a group of hypertensive patients. We enrolled 158 hypertensive subjects (mean age 48&nbsp;±&nbsp;13&nbsp;years) all of which underwent evaluation of the choroidal district by Swept-Source optical coherence tomography (SS-OCT) and 24-h BP monitoring, in order to measure peripheral BP and to estimate central hemodynamic parameters. Inverse significant correlations of clinic PP, 24-h aPP, 24-h aSBP, and 24-h aAIx with thicknesses of central ring, inner ring, and outer ring of the choroid and its overall average were found. The strongest of these correlations was that relating 24-h aPP with overall average choroidal thickness (r&nbsp;=&nbsp;−.531; P&nbsp;&lt;.001). When we divided the study population in subjects with 24-h aPP above and below the median value (35&nbsp;mm Hg), CTh were thinner in subjects with higher values of 24-aPP as compared to those with lower ones, even after adjustment for age, and other potential confounders. The relationships of CTh with 24-h aPP remained significant also taking into account the effects of various covariates in linear multiple regression analyses. Our findings support the concept of a cross-talk between macro- and microcirculation

SUBCLINICAL RENAL DAMAGE IS ASSOCIATED WITH A REDUCED CHOROIDAL THICKNESS IN PATIENTS WITH PRIMARY HYPERTENSION

Objective: The retina is considered the easiest accessible window to study the state of the systemic microcirculation, even if the choroid is the most important vascular layer of the eye. Our understanding of the choroid has been greatly increased in last years since the introduction of advanced techniques of optical coherence tomography (OCT). Our study was aimed to assess choroidal thickness by using Swept-Source OCT (SS-OCT) in essential hypertensive patients (EHs) with and without subclinical renal damage (SRD). Design and method: We enrolled 100 EHs of which 65 without kidney damage and 35 with SRD. In all the participants SS-OCT and a routine biochemical work-up were performed. Glomerular filtration rate (GFR) was estimated by the CKD-EPI equation (eGFR). SRD was defined, by the presence of microalbuminuria or eGFR between 30 and 60\u200amL/min/1.73 m2. OCT measurements were performed according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, that divides the macula into 9 subfields. The circular grid consists of 3 concentric rings. The inner and outer rings are further divided into quadrants: temporal, nasal, superior, and inferior. Design and method: Furthermore, we calculated the average of the individuals values of the four quadrants separately for the inner and the outer ring. The average of all the 9 regions of the ETRDS grid (including the inner, the outer and the central rings) was also calculated. Results: EHs with SRD showed thinner choroidal thicknesses than those without kidney damage (all p\u200a<\u200a0.05), even after adjustment for age (figure). Overall choroidal thickness correlated significantly and directly with eGFR (r\u200a=\u200a0.36) and negatively with urinary albumin excretion (r\u200a=\u200a- 0.39). The association of choroidal thickness with SRD was confirmed in multiple logistic regression analyses once the effect of age, anti-hypertensive therapy and triglycerides was accounted for. The odds ratio of having SRD associated with a standard deviation increase of overall choroidal thickness was 0.43 (0.24\u20130.75, 95% confidence interval; p\u200a=\u200a0.007). Conclusions: Our study confirms the close relationships between changes in ocular microcirculation and renal dysfunction