Ο αυξητικός παράγοντας των ινοβλαστών 23 (FGF-23) στην ομόζυγο β-θαλασσαιμία

Η ομόζυγος β-θαλασσαιμία (βΜΑ) αποτελεί μία κληρονομική αιματολογική νόσο που απαντάται σχετικά συχνά στην Ελλάδα. Χαρακτηρίζεται από εκτεταμένη αιμόλυση, βαριά αναιμία, υπερφόρτωση του οργανισμού με κυτταροτοξικό σίδηρο λόγω συχνών μεταγγίσεων αίματος και πολλαπλές συνοδές επιπλοκές, μέρος των οποίων αποτελεί μία σοβαρή μορφή οστικής νόσου που ταλαιπωρεί την πλειοψηφία των πασχόντων. Μέχρι σήμερα ο μεταβολισμός του φωσφόρου δεν έχει μελετηθεί ικανοποιητικά στους συγκεκριμένους ασθενείς, μολονότι σε μεγάλο αριθμό μελετών υποστηρίζεται η επίδραση των συγκεντρώσεων του κυκλοφορούντος σιδήρου στα επίπεδα και τη δράση του FGF23. Καθώς η βΜΑ αποτελεί μία κατάσταση χρόνιας αιμοσιδήρωσης, είναι πολύ πιθανό στο έδαφος αυτής να ευνοείται η αύξηση της έκκρισης ή/και της δράσης του FGF23 και να ευοδώνεται έτσι η ανάπτυξη φωσφατουρίας, η οποία θα μπορούσε να επιδρά στα παθοφυσιολογικά μονοπάτια της οστικής νόσου της βΜΑ (ΟΝΘ). Η παρούσα διατριβή ερευνά εάν υφίστανται σημαντικές διαφοροποιήσεις στο ακέραιο κλάσμα του FGF23 (iFGF23), στο καρβοξυτελικό θραύσμα αυτού (C-FGF23) και στην πρωτεΐνη Klotho στον ορό των θαλασσαιμικών ασθενών σε σύγκριση με τον υγιή πληθυσμό. Επιπρόσθετα αναζητά πιθανές συσχετίσεις των τριών αυτών παραγόντων με το βαθμό αιμοσιδήρωσης, τη βαρύτητα της ΟΝΘ και το σχήμα αποσιδήρωσης των πασχόντων. Για τον έλεγχο αυτών των ερωτημάτων στρατολογήθηκαν 40 πάσχοντες από βΜΑ και 41 υγιείς μάρτυρες παρόμοιων δημογραφικών χαρακτηριστικών. Από τις συγκρίσεις μεταξύ των ομάδων παρατηρήθηκε ότι οι πάσχοντες εμφανίζουν σε στατιστικά σημαντικό βαθμό χαμηλότερα επίπεδα C-FGF23 στον ορό από τους μάρτυρες. Επιπρόσθετα είχαν υψηλότερες τιμές iFGF23 και χαμηλότερες τιμές Klotho, μολονότι αυτές οι διαφορές δεν κατέστησαν στατιστικά σημαντικές. Τέλος, δε φάνηκε να συσχετίζονται σημαντικά ο βαθμός αιμοσιδήρωσης, η βαρύτητα της ΟΝΘ και το σχήμα αποσιδήρωσης με τα επίπεδα των τριών πρωτεϊνικών παραγόντων στον ορό. Αν και τα ως άνω δεδομένα δεν καταδεικνύουν δυναμικές αλληλεπιδράσεις μεταξύ της βΜΑ και του iFGF23, υποστηρίζουν ότι η αιμοσιδήρωση επιδρά στον FGF23, πιθανότατα αναστέλλοντας την πρωτεολυτική του διάσπαση και οδηγώντας σε μείωση των επιπέδων του C-FGF23. Προτείνεται λοιπόν να διενεργηθούν περαιτέρω παρόμοιες μελέτες σε μεγαλύτερους αριθμούς ασθενών, με σκοπό να διαφωτίσουν πλήρως τη συμμετοχή του FGF23 και της πρωτεΐνης Klotho στην ανάπτυξη της ΟΝΘ.Homozygous beta-thalassemia (βTh) represents an inherited blood disorder relatively common in Greece. It is characterized by extensive hemolysis, severe anemia and cytotoxic iron deposition in the tissues, due to frequent red-cell transfusions. The disease is accompanied by numerous complications, which include a serious form of bone disease that affects the majority of patients. Phosphorus metabolism has not been studied adequately in thalassemic patients until now. As supported by a large number of studies, the serum levels and action of FGF23 are seriously affected by iron concentration in the circulation. Since βTh is characterized by a high iron burden, it is very possible that this condition could increase the secretion and/or action of FGF23, leading to the development of phosphaturia and thereby affecting the pathogenetic pathways of βΤh-bone-disease (TBD). The present dissertation attempts to answer if there are significant differences of intact FGF23 (iFGF23), carboxyl-terminal fragment of FGF23 (C-FGF23) and Klotho protein levels in the serum of patients with βTh compared to the healthy population. In addition, we investigate if any relationship exists between the above factors with the degree of hemosiderosis, the severity of TBD and the iron chelation regimens of the patients. In order to answer these questions, 40 βTh-patients and 41 healthy controls of similar demographic characteristics were recruited in a prospective observational case-control study. From the comparisons between the groups it was observed that the thalassemic patients had statistically significantly lower levels of serum C-FGF23 compared to controls. They also had increased iFGF23 and lower Klotho serum levels, but these observations didn’t reach statistically significance. There were also no correlations between the severity of hemosiderosis, chelation therapy and severity of TBD with the serum levels of iFGF23, C-FGF23 and Klotho. Although our data cannot document dynamic interactions between βTh and iFGF23, they indicate that the chronic presence of hemosiderosis actually interferes to some extent with the metabolism of FGF23, possibly by inhibiting the proteolytic cleavage of iFGF23 and resulting in reduced C-FGF23 levels in serum. Due to the many particularities of the βTh discussed in detail in the main text, further similar studies should take place in a greater number of patients in order to shed more light on the involvement of FGF23 and Klotho protein in the development of TBD

BigO: A public health decision support system for measuring obesogenic behaviors of children in relation to their local environment

Obesity is a complex disease and its prevalence depends on multiple factors related to the local socioeconomic, cultural and urban context of individuals. Many obesity prevention strategies and policies, however, are horizontal measures that do not depend on context-specific evidence. In this paper we present an overview of BigO (http://bigoprogram.eu), a system designed to collect objective behavioral data from children and adolescent populations as well as their environment in order to support public health authorities in formulating effective, context-specific policies and interventions addressing childhood obesity. We present an overview of the data acquisition, indicator extraction, data exploration and analysis components of the BigO system, as well as an account of its preliminary pilot application in 33 schools and 2 clinics in four European countries, involving over 4,200 participants.Comment: Accepted version to be published in 2020, 42nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Montreal, Canad

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Gunshot wounds: A review of ballistics related to penetrating trauma

Civilian gunshot injuries from handgun and rifle ammunition vary in severity depending on the anatomic location involved and the different effects from the ballistic properties of the penetrating projectiles. Ballistic factors such as the impact velocity and energy should not be considered in isolation, as their specific effects are determined by the interaction between the projectile and tissues. Increased tissue damage can result from tumbling of non-deforming rifle bullets and deformation of expanding bullets. Both of these mechanisms increase substantially the energy transfer to the wound and its diameter, also producing a pulsating temporary cavity associated with pressure changes within tissue

A contemporary therapeutic approach to bone disease in beta-thalassemia - a review.

Homozygous beta-thalassemia represents a serious hemoglobinopathy, in which an amazing prolongation in the survival rate of patients has been achieved over recent decades. A result of this otherwise positive evolution is the fact that bone problems have become a major issue in this group of patients. Through an in-depth review of the related literature, the purpose of this study is to present and comment on the totality of the data that have been published to date pertaining to the prevention and treatment of thalassemia bone-disease, focusing on: the contribution of diet and lifestyle, the treatment of hematologic disease and its complications, the management of hypercalciuria, the role of vitamins and minerals and the implementation of anti-osteoporosis medical regimen. In order to comprehensively gather the above information, we mainly reviewed the international literature through the PubMed database, searching for the preventive and therapeutic data that have been published pertaining to thalassemia bone-disease over the last twenty-nine years. There is no doubt that thalassemia bone-disease is a complication of a multi-factorial etiopathology, which does not follow the rules of classical postmenopausal osteoporosis. Bisphosphonates have been the first line of treatment for many years now, with varied and usually satisfactory results. In addition, over the last few years, more data have arisen for the use of denosumab, teriparatide, and other molecules that are in the clinical trial phase, in beta-thalassemia

BigO : A public health decision support system for measuring obesogenic behaviors of children in relation to their local environment

Obesity is a complex disease and its prevalence depends on multiple factors related to the local socioeconomic, cultural and urban context of individuals. Many obesity prevention strategies and policies, however, are horizontal measures that do not depend on context-specific evidence. In this paper we present an overview of BigO (http://bigoprogram.eu), a system designed to collect objective behavioral data from children and adolescent populations as well as their environment in order to support public health authorities in formulating effective, context-specific policies and interventions addressing childhood obesity. We present an overview of the data acquisition, indicator extraction, data exploration and analysis components of the BigO system, as well as an account of its preliminary pilot application in 33 schools and 2 clinics in four European countries, involving over 4,200 participants.</p

Surgical site infection after gastrointestinal surgery in children : an international, multicentre, prospective cohort study

Introduction Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings. Methods A multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI). Results Of 1159 children across 181 hospitals in 51 countries, 523 (45 center dot 1%) children were from high HDI, 397 (34 center dot 2%) from middle HDI and 239 (20 center dot 6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12 center dot 8% (51/397) in middle HDI and 24 center dot 7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI. Conclusion The odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.Peer reviewe