Tolerable rates of visual field progression in a population-based sample of patients with glaucoma.

AIMS: To provide population-based data on the maximum tolerable rate of progression to avoid visual impairment (maxTRoP_VI) and blindness (maxTRoP_BL) from open-angle glaucoma (OAG). METHODS: Participants with OAG in the Thessaloniki Eye Study (cross-sectional, population-based study in a European population) were included in the analysis. Visual impairment was defined as mean deviation (MD) equal to or worse than -12dB and blindness as MD equal to or worse than -24dB. Additional thresholds for visual impairment were tested. For each participant maxTRoP_VI was defined as the rate of progression which would not lead to visual impairment during expected lifetime. MaxTRoP_BL was defined accordingly. Both parameters were calculated for each OAG subject using age, sex, MD and life expectancy data. The eye with the better MD per subject was included in the analysis. RESULTS: Among 135 subjects with OAG, 123 had reliable visual fields and were included in the analysis. The mean age was 73±6 years and the median MD was -3.65±5.28dB. Among those, 69.1% would have a maxTRoP_VI slower than -1dB/year and 18.7% would have a maxTRoP_VI between -1 and -2dB/year. Also, 72.4% would have a maxTRoP_BL slower than -2dB/year. For all tested thresholds for visual impairment, approximately 86% of the OAG study participants would not be able to tolerate a rate of progression equal to or faster than -2dB/year. CONCLUSIONS: The majority of patients with glaucoma in our study would have a maximum tolerable rate of progression slower than -1dB/year in their better eye. Patient-tailored strategies to monitor the visual field are important, but raise the issue of feasibility with regard to the number of visual field tests needed.

Ashtrays and signage as determinants of a smoke-free legislation's success.

INTRODUCTION: Successful smoke-free legislation is dependent on political will, enforcement and societal support. We report the success and pitfalls of a non-enforced nationwide smoke-free legislation in Greece, as well as ways in which compliance and enforcement-related factors, including ashtrays and signage, may impact indoor secondhand smoke (SHS) concentrations. METHODS: A follow-up study of venues (n=150, at baseline, n=75 at 2-year follow-up) in Greece assessed indoor particulate matter with a diameter less than 2.5 micrometers (PM 2.5 ) concentrations attributable to SHS smoke every six months for two years (n=455 venue/measurements). RESULTS: Following the implementation of the 2010 smoke-free legislation, mean PM2.5 concentrations attributable to SHS fell from 175.3 µg/m(3) pre-ban to 84.52 µg/m(3) immediately post-ban, increasing over subsequent waves (103.8 µg/m(3) and 158.2 µg/m(3) respectively). Controlling for potential influential factors such as ventilation, time of day, day of week, city and venue type, all post-ban measurements were still lower than during the pre-ban period (Wave 2 beta: -118.7, Wave 3 beta: -87.6, and Wave 4 beta: -69.9). Outdoor or indoor signage banning smoking was not found to affect SHS concentrations (beta: -10.9, p=0.667 and beta: -18.1, p=0.464 respectively). However, ashtray or ashtray equivalents were strong determinants of the existence of indoor SHS (beta: +67 µg/m(3), p=0.017). CONCLUSIONS: While the public may be supportive of smoke-free legislation, adherence may decline rapidly if enforcement is limited or nonexistent. Moreover, enforcement agencies should also focus on the comprehensive removal of ashtray equivalents that could act as cues for smoking within a venue.

A prospective, non-randomized, no placebo-controlled, phase Ib clinical trial to study the safety of the adipose derived stromal cells-stromal vascular fraction in idiopathic pulmonary fibrosis.

INTRODUCTION: Regenerative medicine and particular adult stem cells represent an alternative option with several fruitful therapeutic applications in patients suffering from chronic lung diseases including idiopathic pulmonary fibrosis (IPF). Nevertheless, lack of knowledge regarding the origin and the potential of mesenchymal stem cells (MSCs) to differentiate into fibroblasts has limited their use for the treatment of this dismal disease. PATIENTS AND METHODS: To this end, we conducted a phase Ib, non-randomized, clinical trial to study the safety of three endobronchial infusions of autologous adipose derived stromal cells (ADSCs)-stromal vascular fraction (SVF) (0.5 million cells per kgr of body weight per infusion) in patients with IPF (n=14) of mild to moderate disease severity (forced vital capacity -FVC>50% predicted value and diffusion lung capacity for carbon monoxide-DLCO>35% of predicted value). Our primary end-point was incidence of treatment emergent adverse events within 12 months. Alterations of functional, exercise capacity and quality of life parameters at serial time points (baseline, 6 and 12 months after first infusion) were exploratory secondary end-points. RESULTS: No cases of serious or clinically meaningful adverse events including short-term infusional toxicities as well as long-term ectopic tissue formation were recorded in all patients. Detailed safety monitoring through several time-points indicated that cell-treated patients did not deteriorate in both functional parameters and indicators of quality of life. CONCLUSIONS: The clinical trial met its primary objective demonstrating an acceptable safety profile of endobronchially administered autologous ADSCs-SVF. Our findings accelerate the rapidly expanded scientific knowledge and indicate a way towards future efficacy trials.

Increased incidence of autoimmune markers in patients with combined pulmonary fibrosis and emphysema.

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is an umbrella term encompassing upper lobe emphysema and lower lobe pulmonary fibrosis with pathogenesis elusive. The aim of our study was to investigate the incidence of autoimmune markers in patients with CPFE. METHODS: In this multicenter study we retrospectively evaluated records from patients with CPFE (n=40) and IPF (n=60) without emphysema. Baseline demographic characteristics, high-resolution computed tomography (HRCT), spirometry, histopathological, treatment, serum immunologic and survival data were investigated. B cell presence was estimated with CD20 immunostaining in representative lung biopsy samples from CPFE patients and control subjects. RESULTS: A statistically significant increased number of CPFE patients with elevated serum ANA with or without positive p-ANCA titers compared to patients with IPF without emphysema was observed. Patients with CPFE and positive autoimmune markers exhibited improved survival compared to patients with a negative autoimmune profile. A massive infiltration of clusters of CD20+ B cells forming lymphoid follicles within the fibrotic lung in CPFE patients with positive serum immunologic profile compared to patients with negative profile, was noted and positively correlated with improved survival. CONCLUSIONS: A significant proportion of patients with CPFE may present with underlying auto-immune disorders that may reside insidiously and be associated with favorable prognosis. Early identification of these patients using a panel of auto-antibodies may lead to more targeted and effective therapeutic applications.

Development and validation of the Greek version of the MNREAD acuity chart.

BACKGROUND: The aim of this study was to develop MNREAD acuity charts in the Greek language (MNREAD-GR) and establish their repeatability in a normal-sighted population. METHODS: One hundred and eighty Greek sentences were constructed based on the design principles of the Minnesota Low Vision Reading Test. The software used to validate them for width was adjusted to the parameters of the non-Latin characters used in the Greek language (MNTest-GR) and width-validated sentences were then checked for literacy by two language teachers. Pilot testing followed in 20 adults and two groups of 20 children. Subsequently, three versions of the MNREAD-GR chart were printed and validated for repeatability: 20 adults read MNREAD-GR charts 1, 2 and 3 in random order over two sessions. A linear mixed-model analysis was performed for near visual acuity (VA), maximum reading speed and critical print size to identify the contribution of each source (individual subject, session, chart and residual error) to the total variance. Subject variance determined the intraclass correlation coefficient. RESULTS: One hundred of the initial 180 sentences were validated with MNTest-GR and approved for literacy correctness. Of those, 57 sentences were selected after pilot testing, and used in the final printed chart in random distribution among three versions. The intraclass correlation coefficients were 0.72 for VA, 0.87 for maximum reading speed and 0.46 for critical print size. The between-charts within-session within-subject component accounted for a maximum five per cent of the variance. The between-sessions within-subject component had a maximum of one per cent. The coefficient of repeatability was 0.08 logMAR for VA, 46.96 words per minute for maximum reading speed and 0.10 logMAR for critical print size. CONCLUSION: The created MNREAD-GR acuity chart is a standardised clinical test that can be used reliably to measure near acuity, reading speed and critical print size in Greek-speaking literate patients of all ages.

Insulin resistance and risk of renal cell cancer: a case-control study.

OBJECTIVE: Obesity and diabetes are considered risk factors for Renal Cell Carcinoma (RCC). We aimed to explore whether insulin resistance (IR) plays an independent role in the development of RCC. DESIGN: In a hospital-based case-control study, we analyzed serum glucose, insulin, leptin and adiponectin levels among 60 incident RCC patients and 236 age- and gender-matched healthy controls. We assessed insulin resistance according to insulin levels, alone or controlled for diabetes mellitus (DM). An alternative measure of insulin resistance, such as the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index, was also assessed with and without controlling for history of DM. We used logistic regression to estimate odds ratios (ORs) adjusted for possible confounders. RESULTS: The positive association of DM and waist to hip ratio as a measure of obesity with RCC was evident in the data set. Insulin levels controlled or not controlled for DM, however, were inversely associated with the risk for RCC; notably, an approximately 40% higher risk was observed in the 1st tertile when compared with the 2nd and 3rd tertile levels of insulin resistance. Similar results were obtained when HOMA-IR was alternatively used. The inverse associations persisted and were even strengthened after controlling for potential confounding factors in multivariate analyses. CONCLUSIONS: Our curdata suggest that insulin resistance may be inversely associated with RCC risk, independently of obesity, DM, lifestyle and hormonal confounding variables. Given the close interconnections among metabolic, inflammatory and immune pathways in RCC causation, it is difficult to infer which process actually initiates a pathologic cascade. The findings should be considered as preliminary data that need to be further confirmed in more appropriate study designs.

Five-year trends of second-hand smoke exposure in Greece: a comparison between complete, partial, and prelegislation levels.

BACKGROUND: Our aim was to assess second-hand smoke (SHS) exposure in hospitality venues after the smoke-free legislation implemented in September 2010 in Greece and to compare with when a partial ban was in place and in 2006 when no ban was in place. METHODS: Hospitality venues were prospectively assessed for their indoor concentrations of particulate matter (PM(2.5)) during the partial ban phase (n=149) and the complete ban phase (n=120, 80% followed up), while overall and matched by venue comparisons were also performed (no ban vs. partial ban vs. complete ban). Comparisons with previously collected data in 2006 when no ban was in place also was performed. RESULTS: Indoor air levels of PM(2.5) attributable to SHS dropped following the transition from a partial to a complete ban by 34% (137 µg/m(3) vs. 90 µg/m(3), p=0.003). This drop was larger in bars (from 195 µg/m(3) to 121 µg/m(3)), than in cafes (124 µg/m(3) vs. 87 µg/m(3)) or restaurants (42 µg/m(3) vs. 39 µg/m(3)). PM(2.5) concentrations between 2006 (no ban) and the partial ban of 2010 were also found to decrease by 94 µg/m(3); however, among matched venues, the levels of indoor air pollution were not found to change significantly (218 µg/m(3) vs. 178 µg/m(3), p=0.58). Comparing the 2010 complete ban results (n=120) with previously collected data from 2006 when no ban was in place (n=43), overall PM(2.5) concentrations were found to fall from 268 µg/m(3) to 89 µg/m(3), while a matched analysis found a significant reduction in PM(2.5) concentrations (249 µg/m(3) vs. 46 µg/m(3), p=0.011). CONCLUSION: The complete ban of smoking in hospitality venues in Greece led to a reduction in SHS exposure, in comparison to when the partial ban or no ban was in place; however, exposure to SHS was not eliminated indicating the need for stronger enforcement.

Stem cell therapy in pulmonary fibrosis.

PURPOSE OF REVIEW: In the last years, we have witnessed an explosion in preclinical data relating to the isolation, differentiation and application of mesenchymal stem cells (MSCs) as a treatment option in animal models of lung fibrosis and inflammation. The scope of this review is to summarize current knowledge regarding the roles of MSCs in lung tissue repair and regeneration and to highlight future therapeutic perspectives and clinical applications in safety and efficacy trials. RECENT FINDINGS: Although there have been interesting studies of cell therapy for diseases of many systems, there has been a paucity of preclinical and clinical studies regarding pulmonary fibrosis. Today, we have made progress with respect to the understanding of the mechanisms of action and application of MSCs in animal models of lung fibrosis as regulators of tissue remodeling and immune response. There are only a few ongoing clinical trials involving MSCs in chronic lung diseases and extrapolation of these data to underline future therapeutic applications in patients with idiopathic pulmonary fibrosis. SUMMARY: Adult MSCs may prove to be a valuable therapeutic option in lung tissue rescue and repair based on their ready availability, immunomodulatory effects and capacity for cell differentiation.

Lady Windermere syndrome after cardiac surgery procedure: a case of Mycobacterium avium complex pneumonia.

We present a patient with Lady Windermere syndrome after coronary bypass operation. To avoid the sternal pain that occurred after every cough episode, this patient used to receive large doses of antitussive drugs. In a poorly drained lung, this usage leads to the development of regions of colonization with Mycobacterium avium complex. It is concerning that the lack of diagnosis for 18 months in this patient occurred because of the insidious symptoms that mimic bronchitis. This case emphasizes how important it is for patients after a median sternotomy to receive adequate analgesic and physiotherapeutic support in order to avoid chronic inflammation and infection of the lungs.

Human bocavirus infections in hospitalized Greek children.

INTRODUCTION: The epidemiology of human bocavirus (HBoV) infections has not been described in Greece, a south-eastern European country. To define the epidemiological profile and the clinical characteristics associated with HBoV infection in a population of children hospitalized with respiratory tract infection. MATERIAL AND METHODS: During a one-year period throat swab samples were collected from 370 previously healthy children, aged 14 days to 13 years, admitted to two different paediatric wards because of respiratory tract infection. Samples were tested for HBoV by PCR amplifying a part of the NS1 gene. RESULTS: Human bocavirus was detected in 12 children (3.2%). Four of the 12 cases were co-infections, 3 of them with influenza A and 1 with coronavirus OC43. Cases were observed only during the cold months. The mean age of children was 1.8 years (range 2 months to 4 years). The most common symptoms were fever, cough and various degrees of respiratory distress. All children were clinically diagnosed as having lower respiratory tract infections, mainly pneumonia and acute laryngotracheobronchitis, and recovered uneventfully. CONCLUSIONS: HBoV infections occur in Greece mostly among very young children. They accounted for 3.2% of children hospitalized with acute respiratory disease. Cases were observed only in late autumn to early spring.

First detection of Rickettsia slovaca in Greece.

Seven hundred and three ticks collected in November and June of 2004-2006 from domestic animals in four localities of Halkidiki prefecture, Northern Greece, were tested for the presence of ricketsial DNA. Rickettsia slovaca was detected in one pool of Rhipicephalus bursa ticks, representing the first report of detection of R. slovaca in Greece.

Suspected Crimean Congo Haemorrhagic Fever cases in Albania.

During 2003 to 2006 samples from 34 Albanian patients with suspected Crimean Congo Hemorrhagic Fever (CCHF) were tested by serology and PCR for CCHF virus; negative samples were further tested for hantaviruses, Leptospira spp. and Rickettsia spp. CCHF virus was detected in 38.2% of cases, hantaviruses in 11.7%, and leptospirosis and rickettsiosis were diagnosed in 29.4% and 2.9% of cases, respectively. There is a seasonal and clinical overlapping among the 4 diseases in Albania, suggesting that testing for these agents is necessary in cases with fever and haemorrhagic manifestations.

Genetic study of the distribution of Greek goat encephalitis virus in Greece.

Tick-borne encephalitis virus (TBEV) and Louping ill virus (LIV) are viruses in the Mammalian tick-borne virus group/genus Flavivirus, causing central nervous system disease. Greek goat encephalitis virus (GGEV), which was isolated from the brain of a newborn goat with neurological symptoms, is currently classified in the TBEV group. The vector of GGEV has not yet been specifically identified but is considered likely to be Ixodes ricinus. A total of 3,144 Ixodidae ticks collected during 2003-2006 from goats and sheep in rural areas of Northern Greece were tested by reverse transcription-polymerase chain reaction (RT-PCR) for the presence of TBEV-specific RNA. Two pools of I. ricinus ticks were shown to be RNA-positive. Sequence analysis showed that the virus was GGEV. The RNA-positive ticks were detected in regions where high prevalence of TBE antibodies in humans was present. Prevalence in ticks varied according to year, season, and geographic region. TBEV is not endemic in Greece, and most probably the seroprevalence of TBE antibodies in humans is due to cross-reactivity to GGEV.

Greek goat encephalitis virus strain isolated from Ixodes ricinus, Greece.

A strain of Greek goat encephaltitis virus was isolated from engorged Ixodes ricinus ticks that had fed on goats in northern Greece. The strain was almost identical to the prototype strain isolated 35 years ago.

Echovirus 15 and autumn meningitis outbreak among children, Patras, Greece, 2005.

BACKGROUND: Enteroviruses are the most common cause of aseptic meningitis, presenting in epidemic or endemic form. OBJECTIVES: To determine the causative agent of an aseptic meningitis outbreak in autumn, 2005 in Patras, Greece. STUDY DESIGN: Cerebrospinal fluid (CSF) samples taken during May 2005-February 2006 from children admitted to the Children Hospital of Patras with signs of aseptic meningitis were tested for the presence of enteroviral RNA. Typing was performed by nucleotide analysis. RESULTS: Enteroviruses were detected in 11 (57.9%) of 19 tested CSF samples. In a 12-day period (27 October-7 November 2005) five aseptic meningitis cases were observed. Echovirus 15 was detected in all five cases, and differed from the prototype strain by 27.6%. Enteroviruses before and after this cluster of cases were of different serotypes (Echovirus 9, Echovirus 6). All patients with Echovirus 15 infection were male with a mean age of 7.7 years (2 months-13 years), all recovered successfully. CONCLUSIONS: This is the first report of a cluster of aseptic meningitis cases caused by Echovirus 15. The causative agent was a new variant of Echovirus 15.

Epidemiological study of tick-borne encephalitis virus in northern Greece.

Serum samples from 921 apparently healthy individuals living in different prefectures of Northern Greece were investigated for the presence of antibodies against tick-borne encephalitis (TBE) virus. In addition, serum and cerebrospinal fluid samples of 302 patients with central nervous system (CNS) infection were tested for the presence of specific IgG and IgM antibodies and TBE virus RNA. Two percent of the general population was found to have antibodies to the virus, with no significant differences among the age groups. Most of the seropositive individuals were male farmers, while seroprevalence varied among different prefectures (0%-5.8%). TBE was not confirmed by laboratory findings in any of the patients with CNS infection. Results of this study revealed that a flavivirus of the TBE serocomplex is circulating in Greece, yet is not a major public health problem.

Epstein-Barr virus DNA in bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis is the most common idiopathic interstitial pneumonia. The human herpesviruses and especially Epstein-Barr virus have been implicated in the etiology of idiopathic pulmonary fibrosis in a number of studies. AIM: The aim of this study was to investigate the potential association between idiopathic pulmonary fibrosis and Epstein-Barr virus. METHODS: Bronchoalveolar lavage fluid and sera were collected from 63 patients out of whom 17 suffered of idiopathic pulmonary fibrosis and 46 of other interstitial lung diseases. Sera from 50 healthy, age-matched individuals were also collected. Antibodies to the early, nuclear, and capsid antigens of Epstein-Barr virus were determined by enzyme immunoassay and indirect immunofluorescence. Additionally polymerase chain reaction was performed in bronchoalveolar lavage fluid in order to investigate the presence of Epstein-Barr virus DNA. Positive polymerase chain reaction results were confirmed by nucleotide sequencing. RESULTS: Statistically significant differences were observed in the frequency of IgA antibodies to viral capsid antigen among patients with idiopathic pulmonary fibrosis, patients with other interstitial lung diseases and healthy controls (60%, 24.4% and 22% respectively, p = 0.013). Epstein-Barr virus DNA was detected in the bronchoalveolar lavage fluid of 3 patients with idiopathic pulmonary fibrosis but in none of the patients with other diseases (p = 0.024). CONCLUSIONS: The results of this study support the association between IPF and EBV, at least in some cases, and provide evidence that BALF is an alternative for the detection of viral DNA in patients with IPF. However further investigation is required concerning the etiology of idiopathic pulmonary fibrosis.