Expanding the potential therapeutic options of hemoperfusion in the era of improved sorbent biocompatibility

Hemoperfusion has been considered a promising adjuvant treatment for chronic diseases and some acute states when specific removal of pathogenic factors from the bloodstream is desired. Over the years, advances in adsorption materials (e.g., new synthetic polymers, biomimetic coating, and matrixes with novel structures) have renewed scientific interest and expanded the potential therapeutic indications of hemoperfusion. There is growing evidence to suggest a prominent place for hemoperfusion as an adjuvant treatment in the setting of sepsis or severe coronavirus disease 2019 and as a therapeutic option for chronic complications associated with accumulated uremic toxins in patients with end-stage renal disease. This literature review will describe the principles, therapeutic perspectives, and the emerging role of hemoperfusion as a complementary therapy for patients with kidney disease

Mass Spectrometry Based Molecular 3D-Cartography of Plant Metabolites

Plants play an essential part in global carbon fixing through photosynthesis and are the primary food and energy source for humans. Understanding them thoroughly is therefore of highest interest for humanity. Advances in DNA and RNA sequencing and in protein and metabolite analysis allow the systematic description of plant composition at the molecular level. With imaging mass spectrometry, we can now add a spatial level, typically in the micrometer-to-centimeter range, to their compositions, essential for a detailed molecular understanding. Here we present an LC-MS based approach for 3D plant imaging, which is scalable and allows the analysis of entire plants. We applied this approach in a case study to pepper and tomato plants. Together with MS/MS spectra library matching and spectral networking, this non-targeted workflow provides the highest sensitivity and selectivity for the molecular annotations and imaging of plants, laying the foundation for studies of plant metabolism and plant-environment interactions

The genomic landscape of ANCA-associated vasculitis: Distinct transcriptional signatures, molecular endotypes and comparison with systemic lupus erythematosus

IntroductionAnti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) present with a complex phenotype and are associated with high mortality and multi-organ involvement. We sought to define the transcriptional landscape and molecular endotypes of AAVs and compare it to systemic lupus erythematosus (SLE).MethodsWe performed whole blood mRNA sequencing from 30 patients with AAV (granulomatosis with polyangiitis/GPA and microscopic polyangiitis/MPA) combined with functional enrichment and network analysis for aberrant pathways. Key genes and pathways were validated in an independent cohort of 18 AAV patients. Co-expression network and hierarchical clustering analysis, identified molecular endotypes. Multi-level transcriptional overlap analysis to SLE was based on our published data from 142 patients.ResultsWe report here that “Pan-vasculitis” signature contained 1,982 differentially expressed genes, enriched in leukocyte differentiation, cytokine signaling, type I and type II IFN signaling and aberrant B-T cell immunity. Active disease was characterized by signatures linked to cell cycle checkpoints and metabolism pathways, whereas ANCA-positive patients exhibited a humoral immunity transcriptional fingerprint. Differential expression analysis of GPA and MPA yielded an IFN-g pathway (in addition to a type I IFN) in the former and aberrant expression of genes related to autophagy and mRNA splicing in the latter. Unsupervised molecular taxonomy analysis revealed four endotypes with neutrophil degranulation, aberrant metabolism and B-cell responses as potential mechanistic drivers. Transcriptional perturbations and molecular heterogeneity were more pronounced in SLE. Molecular analysis and data-driven clustering of AAV uncovered distinct transcriptional pathways that could be exploited for targeted therapy.DiscussionWe conclude that transcriptomic analysis of AAV reveals distinct endotypes and molecular pathways that could be targeted for therapy. The AAV transcriptome is more homogenous and less fragmented compared to the SLE which may account for its superior rates of response to therapy

Availability of assisted peritoneal dialysis in Europe : call for increased and equal access

Background Availability of assisted PD (asPD) increases access to dialysis at home, particularly for the increasing numbers of older and frail people with advanced kidney disease. Although asPD has been widely used in some European countries for many years, it remains unavailable or poorly utilized in others. A group of leading European nephrologists have therefore formed a group to drive increased availability of asPD in Europe and in their own countries. Methods Members of the group filled in a proforma with the following headings: personal experience, country experience, who are the assistants, funding of asPD, barriers to growth, what is needed to grow and their top three priorities. Results Only 5 of the 13 countries surveyed provided publicly funded reimbursement for asPD. The use of asPD depends on overall attitudes to PD, with all respondents mentioning the need for nephrology team education and/or patient education and involvement in dialysis modality decision making. Conclusions and call to action Many people with advanced kidney disease would prefer to have their dialysis at home, yet if the frail patient chooses PD most healthcare systems cannot provide their choice. AsPD should be available in all countries in Europe and in all renal centres. The top priorities to make this happen are education of renal healthcare teams about the advantages of PD, education of and discussion with patients and their families as they approach the need for dialysis, and engagement with policymakers and healthcare providers to develop and support assistance for PD.Peer reviewe

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

Social Movements and International Relations: A Relational Framework

Social movements are increasingly recognized as significant features of contemporary world politics, yet to date their treatment in international relations theory has tended to obfuscate the considerable diversity of these social formations, and the variegated interactions they may establish with state actors and different structures of world order. Highlighting the difficulties conventional liberal and critical approaches have in transcending conceptions of movements as moral entities, the article draws from two under-exploited literatures in the study of social movements in international relations, the English School and Social Systems Theory, to specify a wider range of analytical interactions between different categories of social movements and of world political structures. Moreover, by casting social movement phenomena as communications, the article opens international relations to consideration of the increasingly diverse trajectories and second-order effects produced by social movements as they interact with states, intergovernmental institutions, and transnational actors

Biosynthesis and catabolism of platelet activating factor (paf) in patients with idiopathic glomerulonefritis: in vivo study

The platelet activating factor (PAF) is one of the most potent inflammatory mediators suggesting a potential role during renal injury. The PAF levels depend on biosynthesis and catabolism rate of PAF. The aim of this study is the assessment of PAF, lyso-PAF-acetyl-transferase (lyso-PAF-AT) (enzyme of PAF biosynthesis) and PAF-acetyl-hydrolase (PAF-AH) (enzyme of PAF catabolism) levels, in blood and urine samples of patients with idiopathic glomerulonephritis. Twenty patients with idiopathic glomerulonephritis were included in the study (diagnosis was made by renal biopsies) and 20 healthy subjects as a control group. In the total of the participants the PAF levels were estimated in blood and urine samples by thin-layer chromatographic (TLC) system, PAF identification made by HPLC and PAF quantitification by biological test). The activity of lyso-PAF-AT was measured in blood leucocytes as well as PAF-ΑΗ activity in serum and urine samples. Additionaly the activity of PAF-ΑΤ and PAF-ΑΗ were measured in renal tissue of patients with idiopathic glomerulonephritis and healthy renal tissue of nephrectomised patients with kidney tumor. Acetyl-transferase activity in plasma and urine samples and renal tissue was measured by the trichloroacetid acid precipitation method . Results are as follows: a. PAF levels in patients’ blood were increased compared to control group (p=0,02). b. Lyso-PAF-AT activity in blood leucocytes was not different in patients and control group (p=0,06) a fact which suggests similar PAF biosynthesis in blood leukocytes in these two groups. c. PAF-AH activity in serum samples was increased in patients’ group (p=0,001) as a result of the catabolism of higher PAF blood levels. d. Lyso-PAF-AT activity of renal tissue was increased in patients’ group (p=0,03) a fact which suggests increased PAF biosynthesis in injured renal tissue. PAF-AH activity in renal tissue was not statistically different in these two groups (p=0,14). e. PAF levels and PAF-AH activity was increased in urine samples of patients’ group (p=0,01 και p=0,02, respectively). PAF-AH was positively related with proteinuria (p=0,001). In conclusion the increased PAF levels in patients with idiopathic glomerulonephritis is probably related to increased biosynthesis of PAF in renal tissue and not in blood cells.Ο παράγοντας ενεργοποίησης των αιμοπεταλίων (PAF) είναι ένας ισχυρός φλεγμονώδης μεσολαβητής ο οποίος εμπλέκεται στην πρόκληση της νεφρικής βλάβης. Τα επίπεδα του PAF στον οργανισμό καθορίζονται από το ρυθμό βιοσύνθεσης και αποικοδόμησής του. Σκοπός της μελέτης είναι η μέτρηση των επιπέδων του PAF, του ενζύμου βιοσύνθεσής του, λυσο-PAF-ακετυλοτρασνφεράση (λυσο-PAF-AT) και του ενζύμου αποικοδόμησής του, PAF-ακετυλουδρολάση (PAF-AH), στο αίμα και στα ούρα ασθενών με ιδιοπαθή σπειραματονεφρίτιδα (ΙΣΝ). Στη μελέτη συμμετείχαν 20 ασθενείς με ΙΣΝ (διάγνωση και με βιοψία νεφρού) και 20 υγιείς εθελοντές. Σε όλους τους συμμετέχοντες μετρήθηκαν τα επίπεδα του PAF σε αίμα και ούρα (με χρωματογραφική μέθοδο λεπτού στρώματος (TLC), ταυτοποίησή του με HPLC και ποσοτικοποίησή του έγινε με βιολογικό test). Επίσης μετρήθηκε η δραστικότητα της λυσο-PAF-AT στα λευκοκύτταρα του αίματος καθώς και η δραστικότητα της PAF-ΑΗ στον ορό και στα ούρα. Επιπρόσθετα, προσδιορίσθηκαν η δραστικότητα της λύσο-PAF-ΑΤ και PAF-ΑΗ σε νεφρικό ιστό ασθενών με ΙΣΝ καθώς και σε υγιή νεφρικό ιστό ασθενών που υποβλήθηκαν σε νεφρεκτομή. Η δραστικότητα της ακετυλοτρανσφεράσης στο πλάσμα, στα ούρα και το νεφρικό ιστό έγινε με τη μέθοδο καθίζισης κατόπιν προσθήκης τριχλωροξεικού οξέως. Τα αποτελέσματα έδειξαν: α) ότι τα επίπεδα του PAF στο αίμα των ασθενών ήταν αυξημένα σε σχέση με τους υγιείς εθελοντές (p=0,02) β) η δραστικότητα της λυσο-PAF-AT στα λευκοκύτταρα του αίματος δεν είχε διαφορά (p=0,06) στις δύο ομάδες - ένδειξη παρόμοιας βιοσύνθεσης γ)δραστικότητα PAF-AH του ορού μεγαλύτερη στους ασθενείς (p=0,001) - στην προσπάθεια αποικοδόμησης των αυξημένων επίπεδων PAF δ)δραστικότητα της λυσο-PAF-AT στο νεφρικό ιστό των ασθενών μεγαλύτερη της αντίστοιχης σε υγιή νεφρικό ιστό (p=0,03) - ένδειξη αυξημένης παραγωγής στον πάσχοντα ιστό -, ενώ η PAF-AH δεν είχε διαφορά (p=0,14). ε)τέλος τα επίπεδα του PAF και η δραστικότητα της PAF-AH στα ούρα των ασθενών ήταν υψηλότερα (p=0,01 και p=0,02, αντίστοιχα), ενώ η PAF-AH σχετίζονταν θετικά με τη λευκωματουρία (p=0,001). Συμπερασματικά τα αυξημένα επίπεδα PAF στους ασθενείς με ΙΣΝ φαίνεται ότι οφείλονται σε αυξημένη βιοσύνθεση του στο επίπεδο του νεφρικού ιστού και όχι στα κύτταρα του αίματος

Transforming Growth Factor-beta 1/Smad Signaling in Glomerulonephritis and Its Association with Progression to Chronic Kidney Disease

Introduction: Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine, with diverse roles in fibrosis and inflammation, which acts through Smad signaling in renal pathology. We intended to investigate the expression of TGF-beta/Smad signaling in glomerulonephritis (GN) and to assess its role as risk factor for progression to chronic kidney disease (CKD). Methods: We evaluated the immunohistochemical expression of TGF-beta 1, phosphorylated Smad3 (pSmad3), and Smad7 semiquantitatively and quantitatively using computerized image analysis program in different compartments of 50 renal biopsies with GN, and the results were statistically analyzed with clinicopathological parameters. We also examined the associations among their expressions, the impact of their co-expression, and their role in progression to CKD. Results: TGF-beta 1 expression correlated positively with segmental glomerulosclerosis (p= 0.025) and creatinine level at diagnosis (p = 0.002), while pSmad3 expression with interstitial inflammation (p = 0.024). In glomerulus, concomitant expressions of high Smad7 and medium pSmad3 were observed to be correlated with renal inflammation, such as cellular crescent (p = 0.011), intense interstitial inflammation (p = 0.029), and lower serum complement (C) 3 (p = 0.028) and C4 (p = 0.029). We also reported a significant association between pSmad3 expression in glomerular endothelial cells of proliferative GN (p = 0.045) and in podocytes of nonproliferative GN (p = 0.005). Finally, on multivariate Cox-regression analysis, TGF-beta 1 expression (hazard ratio = 6.078; 95% confidence interval: 1.168-31.627; p = 0.032) was emerged as independent predictor for CKD. Discussion/Conclusion: TGF-beta 1/Smad signaling is upregulated with specific characteristics in different forms of GN. TGF-beta 1 expression is indicated as independent risk factor for progression to CKD, while specific co-expression pattern of pSmad3 and Smad7 in glomerulus is correlated with renal inflammation. (C) 2021 S. Karger AG, Base