Role of the mononuclear cell infiltrate in Graves' orbitopathy (GO): results of a large cohort study.

OBJECTIVE: The extent to which mononuclear cells and TSH-receptor autoantibodies (TRAb) contribute to Graves' orbitopathy (GO) is not completely defined. Here we investigated the relationship between the immunohistochemical phenotype of orbital infiltrating cells and GO features in a large number of patients. METHODS: We conducted an observational cohort study in 76 consecutive patients with GO (16 men and 60 women) who underwent orbital decompression over a period of 18 consecutive months. An ophthalmological evaluation was performed in all patients, as well as immunohistochemistry for CD3, CD4, CD8, CD56 (T-cell markers), CD25 (T and B-cell marker), CD20, CD19 (B-cell markers), and CD138 (plasmacell marker) in specimens collected at decompressive surgery. RESULTS: Having established cutoff values for each marker, cell infiltrates were found in 60 patients (78.9%; CD3: 39.4%, CD4 55.2%, CD8 50%, CD56: 0%, CD25: 28.9%, CD20: 51.3%, CD19: 25%, CD138: 26.3%). Eleven (14.4%) stained exclusively for CD138 (plasmacells). Patients with CD4-positive mononuclear cells had a significantly greater GO clinical activity score (CAS) (mean difference 1.07, 95% CI - 0.33 to - 1.82, P = 0.004 by univariate, P = 0.05 by multivariate analysis). CAS as well as the remaining GO features were not affected significantly by the mononuclear cell subpopulations in multivariate analyses. CONCLUSIONS: Mononuclear cell infiltrates are present in the majority of GO patients, with a small percentage represented exclusively by plasmacells. CD4 cells exert a major role on GO activity. These findings may represent a further advancement in the comprehension of GO pathogenesis.

Effect of participation in a park-based afterschool program on cardiovascular disease risk among severely obese youth.

OBJECTIVES: The prevalence of severe obesity in youth is rising, despite reports of obesity rates stabilizing overall. While reports on treatment outcomes for youth with severe obesity (bariatric surgery, behavioral and pharmacological treatments) exist, very few community-based programs have reported changes in health outcomes in this population. We assessed changes in cardiovascular health risk profiles among racial/ethnic minority youth with severe obesity who participated in Fit2Play™, a park-based afterschool health promotion program. STUDY DESIGN: A longitudinal cohort study. METHODS: Children aged 6-14 years (N = 1546, 51% Hispanic, 44% non-Hispanic black) who participated in the Fit2Play™ in one of 34 urban park sites for one school year over five separate school years (2010-2015) had height, weight, four-site skinfold thicknesses, systolic blood pressure (SBP)/diastolic blood pressure (DBP), fitness tests, and a health/wellness knowledge test collected at the beginning and end of the school year. Two-level repeated measures mixed models examined changes in cardiovascular health outcomes (body mass index [BMI], skinfold thickness, systolic/diastolic blood pressure percentile [SBPP/DBPP], cardiorespiratory fitness [PACER]) in youth with severe obesity over 1- and 2-year follow-up. RESULTS: Compared with baseline, BMI decreased 13% (incidence rate ratio [IRR] 95% confidence interval [CI]: 0.83-0.90), sumof skinfold thicknesses decreased 5% (IRR 95% CI: 0.91-0.99), SBPP decreased 5% (IRR 95% CI: 0.90-0.99), DBPP decreased 19% (IRR 95% CI: 0.77-0.86), and PACER scores increased 12% (IRR 95% CI: 1.0-1.27) after two years of participation in the Fit2Play™ program. CONCLUSIONS: Findings here support community/park-based youth programs as effective and accessible treatment options for reducing cardiovascular disease risk among youth with severe obesity.

Antioxidant effects of ß-carotene, but not of retinol and vitamin E, in orbital fibroblasts from patients with Graves' orbitopathy (GO).

BACKGROUND: Oxidative stress is involved in the pathogenesis of Graves' orbitopathy (GO) and several antioxidant agents, namely, selenium, quercetin, enalapril, vitamin C, N-acetyl-L-cysteine, and melatonin, have been shown to reduce oxidative stress and its consequences in primary culture of orbital fibroblasts. In addition, selenium is effective for the treatment of mild GO. Here, we investigated the action of three additional antioxidants in orbital fibroblasts, namely, retinol, ß-carotene, and vitamin E. METHODS: Primary cultures of orbital fibroblasts were established from GO patients and control subjects. To induce oxidative stress, cells were treated with H2O2, after which glutathione disulfide (GSSG) (a parameter of oxidative stress), cell proliferation, hyaluronic acid, TNFα, IFNγ, and IL1ß were measured. RESULTS: H2O2-dependent oxidative stress (augmented GSSG) was associated with increased cell proliferation and cytokine release. All the three antioxidant substances reduced GSSG in both GO and control fibroblasts. ß-carotene reduced proliferation in GO, but not in control fibroblasts. IL1ß was reduced by all three substances. Retinol reduced IFNγ in GO and control fibroblasts. CONCLUSIONS: Our study supports an antioxidant role of retinol, ß-carotene, and vitamin E in orbital fibroblasts from patients with GO and provides a basis for a possible clinical use these substances.

Action of three bioavailable antioxidants in orbital fibroblasts from patients with Graves' orbitopathy (GO): a new frontier for GO treatment?

OBJECTIVE: Oxidative stress is involved in the pathogenesis of Graves' orbitopathy (GO) and an antioxidant approach has been advocated for GO treatment. Here, we investigated the action of three antioxidants in orbital fibroblasts, namely, vitamin C, N-acetyl-L-cysteine, and melatonin. METHODS: Primary cultures of orbital fibroblasts from six GO patients and six control subjects were established. Cells were treated with H2O2 to induce oxidative stress. Cell vitality assays were performed to determine the non-cytotoxic dose of each antioxidant. The following assays were performed: glutathione disulfide (GSSG), as a measure of oxidative stress, cell proliferation, hyaluronic acid (HA), TNFα, IFNγ, and IL1ß. RESULTS: H2O2 induced oxidative stress (augmented GSSG), increased cell proliferation as well as cytokine release, but did not affect HA release. All of the three antioxidant substances reduced H2O2-dependent oxidative stress. Vitamin C reduced proliferation in GO, but not in control fibroblasts. N-acetyl-L-cysteine reduced proliferation and IFNγ in GO, and HA and IL1ß in both GO and control fibroblasts. Melatonin reduced IL1ß and HA in GO and control fibroblasts, and IFNγ only in GO fibroblasts. CONCLUSIONS: Our study provides evidence in support of an antioxidant role of vitamin C, N-acetyl-L-cysteine and melatonin in orbital fibroblasts. Some of the effects of these compounds are exclusive to GO fibroblasts, whereas some other are observed also in control fibroblasts. Our observations provide a basis for a possible clinical use of these substances in patients with GO.

Synthesis and antioxidant evaluation of lipophilic oleuropein aglycone derivatives.

Oleuropein is the most important phenolic compound present in olive cultivars, but it is scarcely present in extra virgin olive oil (EVOO) due to its high hydrophilicity and degradability. Thus, a set of oleuropein aglycone derivatives were synthesized by transacetylation under mild conditions with the aim of circumventing these drawbacks and making the active moiety in oleuropein suitable to be added to food fats. The oleuropein aglycone (closed ring form) is obtained by hydrolyzing oleuropein using Lewis acid catalysis. Then, the permeation profiles as well as the antioxidant capacity of the oleuropein aglycone derivatives were evaluated by ORAC, DPPH assays and by ROS formation using the SH-SY5Y cell line. The biological activities of the obtained compounds exhibited a dependence on their level of lipophilicity.

Randomized clinical trial of psychological support and sleep adjuvant measures for postoperative sleep disturbance in patients undergoing oesophagectomy.

BACKGROUND: Major surgery such as oesophagectomy requires a postoperative stay in intensive care. Painful stimuli lead to sleep disturbance and impairment in quality of life. The aim of this study was to evaluate the effect of psychological counselling and sleep adjuvant measures on postoperative quality of sleep and quality of life. METHODS: This RCT was performed between January 2013 and October 2015. Patients undergoing oesophagectomy for cancer were randomized into one of four groups receiving: psychological counselling plus sleep adjuvant measures during the ICU stay; psychological counselling alone; sleep adjuvant measures alone during the ICU stay; or standard care. The primary endpoint was impairment in quality of life measured using the European Organisation for Research and Treatment of Cancer C30-QL2 questionnaire between admission for surgery and discharge from hospital. The secondary endpoint was impairment in quality of sleep assessed by means of the Pittsburgh Sleep Quality Index between admission for surgery and hospital discharge. RESULTS: The local ethics committee approved the early termination of the study because of relevant changes in the ICU setting. Some 87 patients were randomized and 74 patients were evaluated in the analysis. Psychological counselling reduced the impairment in quality of life (odds ratio 0·23, 95 per cent c.i. 0·09 to 0·61) and in quality of sleep (odds ratio 0·27, 0·10 to 0·73). CONCLUSION: Perioperative psychological support reduces impairment in quality of life and quality of sleep after oesophagectomy. Registration number: NCT01738620 (http://www.clinicaltrials.gov).

Does early response to intravenous glucocorticoids predict the final outcome in patients with moderate-to-severe and active Graves' orbitopathy?

PURPOSE: Intravenous glucocorticoids (ivGCs) given as 12-weekly infusions are the first-line treatment for moderate-to-severe and active Graves' orbitopathy (GO), but they are not always effective. In this study, we evaluated whether response at 6 weeks correlated with outcomes at 12 (end of intervention) and 24 (follow-up) weeks, particularly in patients initially unresponsive. METHODS: Our database (Bartalena et al. J Clin Endocrinol Metab 97:4454-4463, 10), comprising 159 patients given three different cumulative doses of methylprednisolone (2.25, 4.98, 7.47 g) was analyzed, pooling data for analyses. Responses at 6 weeks were compared with those at 12 and 24 weeks using three outcomes: overall ophthalmic involvement [composite index (CI)]; quality of life (QoL); Clinical Activity Score (CAS). Responses were classified as "Improved", "Unchanged", "Deteriorated", compared to baseline. RESULTS: Deteriorated patients at 6 weeks for CI (n = 8) remained in the same category at 12 weeks and 7/8 at 24 weeks. Improved patients at 6 weeks for CI (n = 51) remained in the same category in 63% and 53% of cases at 12 and 24 weeks, respectively. Unchanged patients at 6 weeks (n = 100) eventually improved in 28% of cases (CI), 58% (CAS), 32% (QoL). There was no glucocorticoid dose-dependent difference in the influence of early response on later outcomes. CONCLUSIONS: Patients who deteriorate at 6 weeks after ivGCs are unlikely to benefit from continuing ivGCs. Patients unresponsive at 6 weeks still have a significant possibility of improvement later. Accordingly, they may continue ivGC treatment, or, alternatively, possibly stop ivGCs and be switched to a second-line treatment.

Graves' orbitopathy, idiopathic orbital inflammatory pseudotumor and Epstein-Barr virus infection: a serological and molecular study.

OBJECTIVE: One of the hypotheses on the pathogenesis of autoimmune diseases, including Graves' disease (GD) and Graves' orbitopathy (GO), involves bacterial or viral infections. Recently, Epstein-Barr virus (EBV) has been proposed to play a role in the pathogenesis of idiopathic orbital inflammatory pseudotumor (IOIP) in Asians. The aim of the present study was to investigate the possible association of GO with EBV infection/exposure, as compared with IOIP, using serum and tissue samples, as well as primary cultures of orbital fibroblasts. METHODS: Thirty-one patients were studied, including four with IOIP, ten with GO, nine with GD without GO and eight control patients without IOIP, GD and GO. All patients with IOIP and GO underwent orbital decompression. Control patients underwent palpebral surgery. Fibroadipose orbital tissue samples were collected. Serum anti-EBV antibodies were measured in all patients. EBV-DNA was measured in blood samples, orbital tissue samples and primary cultures of orbital fibroblasts. RESULTS: Serum assays showed that the vast majority of patients have had a previous exposure to EBV, but no one had an acute infection. EBV-DNA was detected in ~40% of blood samples from GO, GD and control patients, but in none of the IOIP samples. EBV-DNA was not detected in any of the orbital tissue samples tested or in primary cultures of orbital fibroblasts. CONCLUSIONS: EBV infection does not seem to be associated with GD, GO and IOIP in Caucasians. Whether EBV is involved in IOIP in Asians or other populations remains to be confirmed.

Implementación y evaluación de un programa de gestión de calidad para el monitoreo de glucómetros en un hospital universitario / Implementation and evaluation of a management program quality for monitoring glucometers in a hospital academic

Introducción: El uso de dispositivos portátiles para controlar la glucemia se ha extendido en los últimos años a las entidades hospitalarias, porque proporcionan un resultado rápido al realizarse al lado de la cama del paciente (point-of-care testing). Objetivo: Describir el proceso y los resultados de la implementación de un programa de gestión de calidad para el control de glucómetros hospitalarios. Materiales y Métodos: Se presenta la implementación de un programa de gestión de calidad para evaluar 50 glucómetros pertenecientes a siete áreas críticas del Hospital Italiano de Buenos Aires (Unidad Coronaria, Terapia Intensiva de Adultos y Pediátrica, Terapia Intermedia, Central de Emergencias de Adultos y Pediátrica, Unidad de Cuidados Intensivos Neonatológicos), desde el 1 de enero de 2014 hasta la actualidad, basado en tres estrategias: control diario, análisis mensual (precisión y exactitud) y control de muestras paralelas. Resultados: Luego de instaurar este programa y analizar los datos de los primeros 17 meses, se requirió un recambio total de 292 glucómetros: 150 debido al control de calidad diario, 119 por el análisis mensual y 23 por el control de muestras paralelas. Esto implicó retirar 17/50 glucómetros por mes. Conclusiones: Si bien estos dispositivos son útiles por su rápida respuesta, el 34,6% debió ser reemplazado por no haber superado alguno de los requisitos planteados en las estrategias de evaluación. La peor performance fue en los niveles de hipoglucemia, situación de interés para la rápida toma de decisiones. Es importante destacar la necesidad de aplicación de un plan de calidad para glucómetros sobre la base de un diseño propio y a medida de la institución para garantizar la seguridad del paciente.(AU)

Introduction: The use of portable devices for glycemic control has been extended in recent years to hospital entities, because they provide a rapid result when they are performed at or near the patient's bedside (point of care testing). Objective: To describe the process and results of the implementation of a quality management program to control of hospital glucometers. Materials and Methods: We present the implementation of a quality management program to evaluate 50 glucometers belonging to seven critical areas of Hospital Italiano de Buenos Aires (Coronary Unit, Adult and Pediatric Intensive Care Unit, Intermediate Therapy, Adult and Pediatric Emergency Center, Unit of Neonatal Intensive Care), from January 1, 2014 to the present, based on three strategies: Daily Control, Monthly Analysis and Control of Parallel Samples. Results: After implementing this program and analyzing the first 17 months, the substitution of 292 glucometers was required: 150 due to daily quality control, 119 per monthly analysis and 23 due to control parallel samples. This involved withdrawing 17/50 glucometers monthly. Conclusions: Although these devices are useful because of their rapid response, 34.6% had to be replaced because they exceeded the requirements presented in the evaluation strategies. The worst performance was in levels of hypoglycemia, a situation of interest for rapid decision-making. It is important to emphasize the need to apply a quality plan for glucometers based on an own design and suitable for the institution to guarantee the safety of the patient.(AU)

Long-term outcome of Graves' orbitopathy following high-dose intravenous glucocorticoids and orbital radiotherapy.

OBJECTIVE: Intravenous (iv) glucocorticoids (GC) (ivGC) and orbital radiotherapy (ORT) are commonly used in active Graves' orbitopathy (GO), with favorable outcomes in up to 80% of patients. However, little is known on the factors that may affect GO outcome in the long term, an issue that we investigated here. METHODS: We studied retrospectively 96 untreated patients with GO, identified out of 787 consecutive patients who came to our GO Clinic for a follow-up visit between September 2010 and June 2013. After the first observation, patients were treated with ivGC and ORT and were then re-examined after a median period of 55.5 months. The primary end-point was the possible relation between GO outcome and several individual variables. RESULTS: Exophthalmometry, eyelid aperture, CAS, diplopia and visual acuity (the latter only in patients with an initial reduction) improved significantly after treatment. Overall, 67.7% of patients had improved and were considered as responders, whereas the remaining (29.1% stable and 4.5% worsened) were considered as non-responders. Age, smoking, thyroid volume, thyroid treatment, serum anti-TSH receptor autoantibodies and individual GO features at first observation did not affect the outcome of GO, which, in contrast, was affected by gender and by the time elapsed between first and last observation. Thus, the prevalence of responders was higher in females (76.4 vs 48% in males, P = 0.02) and the time elapsed between first and last observation was greater in responders (58 vs 39 months in non-responders, P = 0.02). Whereas the prevalence of responders and non-responders was similar up to 36 months, there was an increase in responders beginning between 37 and 48 months and reaching a peak of ~80% between 61 and 72 months, to plateau thereafter. CONCLUSIONS: Given the limitations of retrospective investigations, our study confirms that the combination of GC and ORT is effective in GO and shows that females have greater chances to respond to treatment. The notorious tendency of GO to improve spontaneously with time most likely contributes the long-term outcome of the eye syndrome.

Total thyroidectomy for Graves' disease treatment.

OBJECTIVES: Graves' disease (GD) is the most common cause of hyperthyroidism, and accounts worldwide for 60-80% of all cases. The diagnosis is based on clinical findings, and is confirmed by the presence of TRAB, suppression of TSH, and elevation of free thyroxin (free T4), and triiodinethyronin (free T3). GD can be treated by antithyroid drugs, radioactive iodine, or surgery. The aim of this study was to review retrospectively the surgical management, in terms of safety and efficacy, in 50 patients operated in the Department of Surgical Sciences since 2005 through 2010 and followed up at the Endocrinology Unit A of the Experimental Medicine Department. We assessed postoperative complications, which included the presence, persistence and development of ophthalmopathy, transient hypocalcemia, permanent hypoparathyroidism and recurrent laryngeal nerve palsy. MATERIALS AND METHODS: We analyzed data from 50 patients with GD who were eligible and underwent Total Thyroidectomy (TT). Thirty-nine patients underwent TT for recurrent hyperthyroidism after medical therapy and eleven patients for severe ophtalmopathy. The mean follow up was 41 months (range: 10-70). RESULTS: Eleven patients had ophtalmopathy before surgery. Four patients developed an ophtalmopathy after surgery. Eleven patients presented hypocalcemia, transient in ten patients and permanent in one patient. Five patients developed a transient disphony. Conclusions. Total thyroidectomy is a safe and radical procedure in Graves' disease treatment. Complications of TT are not different than subtotal thyroidectomy if it's performed by expert surgeons.

Surgical strategies in patients with medullary thyroid carcinoma.

OBJECTIVES: Aim of the study was to identify, in 59 operated patients affected by medullary thyroid carcinoma (MTC), the recurrence rate, survival, mortality and incidences of surgically derived hypoparathyroidism and recurrent laryngeal nerve injury (RLNI). MATERIALS AND METHODS: Based on pre-surgical diagnosis of the 59 patients included in the study, 35 underwent total thyroidectomy with central neck dissection (Group A), 14 total thyroidectomy, central neck dissection and monolateral functional neck dissection (Group B) and 10 total thyroidectomy central neck dissection, bilateral functional neck dissection (Group C). Overall survival, recurrences, incidence of hypoparathyroidism and RLNI were evaluated. RESULTS: The survival and recurrences were not statistically different among the three Groups. In Group B there was major probability of re-operation (p=0.042). The mortality rate was clearly major in Group C (p=0.003) due to the stage of pathology. Group C showed a high number of hypoparatiroidism compared to Group B, and B compared to A. In Group A there was only one unexpected RLNI; in 5 cases, 3 in Group B and 2 in Group C, there were a necessity laringeal section due to nerve tumor involvement. CONCLUSIONS: From our data it appears clearly that disease outcome following the different surgical approaches is mainly determinated by the stage of the disease at diagnosis. However, the finding that patients in Group A and B showed a high rate of local-regional recurrences may suggest that homolateral lymphadenectomy in Group A patients and bilateral lymphadenectomy in Group B patients should be always performed.

Anti-inflammatory effect of 3,4-DHPEA-EDA [2-(3,4 -hydroxyphenyl) ethyl (3S, 4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate] on primary human vascular endothelial cells.

Diets in which fat is significantly provided by olive oil and are relatively rich in vegetables, have been associated with a low incidence of cardiovascular diseases, mostly due to the presence of several phenolic compounds which have anti-oxidant and antiinflammatory properties. [1]. In this work, we describe the anti-inflammatory effect of 3,4-DHPEA-EDA in a cell model that we developed to mimic inflammatory injury of endothelium. This was based on the production of the proinflammatory chemokine CCL2, following in vitro stimulation of primary human endothelial cells. Pre-treatment of cells with 3,4-DHPEA-EDA resulted in a dose-dependent inhibition of CCL2 secretion. The effect of 3,4-DHPEA-EDA on CCL2 expression was observed at the transcriptional level. Functional data have shown that 3,4-DHPEA-EDA diminished monocyte adhesion to HUVECs. These results point on the use of 3,4- DHPEA-EDA as a novel drug aimed to prevent or reduce inflammation of endothelium.

Subfascial endoscopic perforator surgery (SEPS) in chronic venous insufficiency. A 14 years experience.

INTRODUCTION: Subfascial Endoscopic Perforator Surgery (SEPS) enables the direct visualization and section of perforating veins. Morbidity and duration of hospitalization are both less than with conventional open surgery (Linton's or Felder's techniques). PATIENTS AND METHODS: A total of 322 legs from 285 patients with a mean age of 56 years (range 23-90) were treated at our Department from May 1996 to January 2010. In 309 cases, an endoscope (ETM Endoskopische Technik GmbH, Berlin, Germany) was introduced through a transverse incision approximately 1.5 cm in length and 10 cm from the tibial tuberosity, as with Linton's technique. A spacemaker balloon dissector for SEPS, involving a second incision 6 cm from the first, was used in only 13 cases. RESULTS: The procedure used in each case was decided on the basis of preoperative evaluation. SEPS and stripping were performed in 238 limbs (73.91%), SEPS and short stripping in 7 limbs (2.17%), SEPS and crossectomy in 51 limbs (15.84%), and SEPS alone in 26 limbs (8.07%). 103 patients presented a total of 158 trophic ulcers; the healing time was between 1 and 3 months, with a healing rate of 82.91% after 1 month and 98.73% after 3 months. CONCLUSION: Subfascial ligature of perforating veins is superior to sclerotherapy and minimally invasive suprafascial treatment for the treatment of CVI. It is easy to execute, minimally invasive and has few complications.

Centrifugation speed affects light transmission aggregometry.

BACKGROUND: Light transmission aggregometry (LTA) is considered the gold standard for investigating platelet activity ex vivo. However, LTA protocols are not standardized, and differences in LTA procedure are a potential source of variance in results. Centrifugation speed is an essential component of platelet preparation in LTA, has yet to be standardized, and may affect platelet aggregation results. We sought to investigate the effect of relative centrifugal force (RCF) intensity on LTA results. METHODS: Ten healthy controls had venous blood drawn and centrifuged at 150, 200, 300, and 500 g for 10 min. Cell counts in whole blood and platelet-rich plasma (PRP) were measured using a hematology analyzer. LTA was performed using 1.0 µm adenosine diphosphate (ADP) and 0.4 µm epinephrine as an agonist. Aggregation (%) was compared at 60, 120, 180, and 300 s and at maximum aggregation. RESULTS: Centrifugation speed was associated with decreasing platelet count (P < 0.001) and decreasing mean platelet volume (P < 0.001) in PRP. Maximum aggregation decreased with increasing speeds for ADP 1.0 µm (150 g- 89%, 200 g- 93%, 300 g- 71%, 500 g- 17%; P < 0.001). Similar findings were noted at 120 s (150 g- 69%, 200 g- 50%, 300 g- 35%, 500 g- 12%; P < 0.001), 180 s (150 g- 82%, 200 g- 74%, 300 g- 44%, 500 g- 13%; P < 0.001), and 300 s (150 g- 85%, 200 g- 88%, 300 g- 55%, 500 g- 14%; P < 0.001). Consistently, platelet aggregation in response to epinephrine 0.4 µm decreased significantly with increasing centrifuge RCF at 60, 120, 180, 300 s and at maximum aggregation (P < 0.05 for each comparison). CONCLUSION: Our data demonstrate the importance of centrifugation speed in the interpretation of LTA results, supporting the need for standardization of centrifugation RCF in LTA protocols.

Short-term changes in the optic nerve head and visual field after trabeculectomy.

UNLABELLED: AIMS OR PURPOSE: To evaluate short-term changes in optic nerve head topography and visual field induced by surgical reduction of intraocular pressure. METHODS: A prospective study was performed on 56 eyes of 56 patients with uncontrolled primary open-angle glaucoma despite maximum medical therapy, which underwent trabeculectomy. Optic nerve head evaluations by means of Heidelberg Retina Tomograph, and visual field tests were performed pre-operatively, and at 3 and 6 months after surgery. Differences in intraocular pressure, visual field indices, and Heidelberg Retina Tomograph parameters were evaluated with the t-test for paired data. A linear regression model was calculated to analyze the relationship between intraocular pressure reduction and visual field changes, and optic nerve head changes. RESULTS: Mean intraocular pressure decreased from 24.4 ± 5.0 mm Hg to 12.1 ± 3.1 mm Hg (month 3, P<0.001), and 10.6 ± 2.8 mm Hg (month 6, P<0.001) after trabeculectomy. Mean retinal nerve fiber layer thickness (baseline, 0.19 ± 0.034; month 3, 0.24 ± 0.039, P=0.05; month 6, 0.21 ± 0.037, P=0.05) showed a statistical significant change compared with baseline values. CONCLUSIONS: In this 6-months study, a significant increase in retinal nerve fiber layer thickness was detected after glaucoma filtration surgery.

Carboplatin and gemcitabine combination in metastatic triple-negative anthracycline- and taxane-pretreated breast cancer patients: a phase II study.

Triple-negative breast cancer (TNBC) is characterized by lack of hormone receptors and HER-2 and shares many features with BRCA1-associated cancer. Preclinical data indicate cisplatin sensitivity, suggesting that these tumors may have defects in the BRCA1 pathway. The carboplatin and gemcitabine (CG) combination is active in unselected anthracycline/taxane pretreated metastatic breast cancer patients, so we carried out a phase II study to evaluate the activity of the CG combination in pretreated metastatic TNBC patients. From 10/2004 to 3/2009 we enrolled 31 patients. Median age was 57 years and 29 patients out of 31 had visceral involvement. The overall response rate (ORR) was 32% (1 complete response /9 partial responses), in addition 5 patients obtained stable disease for >12 weeks. After a median follow-up of 34 months, all patients progressed with a median time to progression of 5.5 months and median overall survival of 11 months. Dose reductions, delays and omissions occurred in 75 (60%), 36 (29%) and 22 (18%) cycles. Grade 3/4 neutropenia occurred in 17 and febrile neutropenia in 4 patients. Ten patients had Grade 3/4 thrombocytopenia. Non hematological toxicities were manageable. The CG combination is a reasonable option for the treatment of metastatic pretreated TNBC patients.

HIV-1 Tat-induced platelet activation and release of CD154 contribute to HIV-1-associated autoimmune thrombocytopenia.

BACKGROUND: Enhanced platelet activation in human immunodeficiency virus (HIV)-1-infected patients has been reported and shown to strongly correlate with plasma viral load. Activated platelets are known to express and to release a variety of proteins that can modulate the immune system. Specifically, platelet-derived CD154 has been shown to be directly involved in the development of autoimmune thrombocytopenia (ITP). The mechanism by which HIV-1 infection leads to platelet activation and the effect of this activation on the development of HIV-1 ITP, however, is not fully understood. OBJECTIVE: We have investigated the effect of HIV-1 Trans activating factor (Tat) on platelet activation. RESULTS: We report that HIV-1 Tat directly interacts with platelets and induces platelet activation resulting in platelet micro-particle release. This activation by Tat requires the chemokine receptor CCR3 and ß3-integrin expression on platelets, as well as calcium flux. Tat-induced activation of platelets releases platelet CD154, an immune modulator. Enhanced B-cell activity is found in mouse spleen B cells co-cultured with platelets treated with Tat in vitro. An early antibody response against adenovirus is found in Tat-injected mouse immunized with adenovirus, suggesting an enhanced immune response in vivo. CONCLUSIONS: We have described a role of Tat-induced platelet activation in the modulation of the immune system, with implications for the development of HIV-1-associated thrombocytopenia.