Elevated serum triglycerides is the strongest single indicator for the presence of metabolic syndrome in patients with type 2 diabetes

BACKGROUND: Patients with diabetes already fulfill one diagnostic criterion for MS according to the existing classifications. Our aim was to identify one single clinical parameter, which could effectively predict the presence of MS in patients with type 2 diabetes. METHODS: We studied all patients with type 2 diabetes who attended our Diabetes Outpatient Clinic during a three-month period. Waist circumference, blood pressure and serum lipids were measured. Establishment of MS diagnosis was based a) on National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria and b) on International Diabetes Federation (IDF) criteria. Receiver operating characteristic (ROC) analysis was applied in order to identify the clinical parameter with the highest predictive capability for MS. Among the 500 participating patients (231 males, 269 females), MS was diagnosed in 364 patients (72.8%) according to the NCEP ATP III criteria and in 408 patients (81.6%) according to the IDF criteria. RESULTS: For the NCEP ATP III classification, serum triglycerides (in the overall population), waist and HDL (in female population) demonstrated the highest predictive capability for MS (AUCs:0.786, 0.805 and 0.801, respectively). For the IDF classification, no single parameter reached an AUC > 0.800 in the overall population. In females, HDL displayed a satisfactory predictive capability for MS with an AUC which was significantly higher than the one in males (0.785 vs. 0.676, respectively, p < 0.05). CONCLUSION: Elevated serum triglycerides strongly indicate the presence of MS in patients with type 2 diabetes. In female patients with type 2 diabetes, central obesity was the second stronger predictor of MS besides hypertriglyceridemia

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

TACI and sepsis in critically ill patients in the ICU: genetic polymorphisms of innate and adaptive immunity as predictors of outcome in critically ill patients

Objective: Our study investigated potential associations of genetic polymorphisms of innate and adaptive immunity factors with development of sepsis and mortality of patients admitted in an intensive care unit (ICU).Methods: All patients admitted in our 8-bed medical/surgical ICU were prospectively followed until the ICU outcome (discharge from the ICU, death in the ICU). For innate immunity, we studied two single-nucleotide polymorphisms (SNPs) of toll-like receptor 4 (TLR4-D299G and TLR4-T399I) and one SNP causing complement deficiency (C2del28bp). For adaptive immunity, we studied two SNPs of BAFF-R (BAFF-R-H159Y and BAFF-R-P21R) and one SNP of TACI (TACI-C104R). Polymorphisms were detected by allele-specific polymerase chain reaction followed by restriction fragment length polymorphism.Results: Two hundred fifteen patients (148 males, 67 females) were included in the study (94 medical, 46 surgical and 75 trauma patients). Age (mean±SD) was 54.1±19.7 years, APACHE II score at admission in the ICU 22.0±6.0 and SOFA score at admission in the ICU 9.7±3.5. ICU-acquired sepsis was recorded in 108 patients (50.2%) and ICU mortality was 20.5% [95% confidence interval (CI) 15.0–25.9]. TLR4 SNPs were detected in a co-segregated state. Carriage of either TLR4 SNP and carriage of BAFFR-P21R were independently associated with lower probability of ICU-acquired sepsis compared with wild-type homozygotes [adjusted odds ratios 0.32, 95%CI 0.12–0.86, p=0.024 for TLR4-T399I, 0.34, 95%CI 0.13–0.94, p=0.037 for TLR4-T399I and 0.44, 95%CI 0.20–0.97, p=0.044 for BAFFR-P21R]. This inverse association of TLR4 SNPs with sepsis applied to medical and trauma patients, while in surgical patients no association was recorded. Carriage of TACI-C104R SNP was an independent predictor of ICU mortality after adjustment for significant confounders [hazard ratio 5.01 (1.14–22.03, p=0.033). BAFFR-H159Y SNP displayed no significant associations with ICU-acquired sepsis or ICU mortality, while C2del28bp was not detected in our patient sample.Conclusions: In our sample of critically ill patients TLR4 polymorphisms and BAFFR-P21R predicted a lower probability of ICU-acquired sepsis and TACI-C104R polymorphism was an independent predictor of ICU mortality. Innate and adaptive immunity genetic polymorphisms may influence the outcome of critically ill patients.Σκοπός: ο προσδιορισμός των γενετικών πολυμορφισμών των μορίων TACI, BAFF και TLR4 και η διερεύνηση πιθανής συσχέτισής τους με την εμφάνιση σήψης και τη θνητότητα σε ασθενείς που εισάγονται στη ΜΕΘ. Ασθενείς-Μέθοδος: Προοπτική μελέτη παρακολούθησης όλων των ασθενών που εισήχθησαν στη Μονάδα Εντατικής Θεραπείας μέχρι την έκβαση (έξοδος, θάνατος). Για τη φυσική ανοσία μελετήθηκαν δύο πολυμορφισμοί του toll-like receptor 4 (ΤLR4-D299G και TLR4-T399I) και ένας πολυμορφισμός του C2 που προκαλεί ανεπάρκεια συμπληρώματος (C2del28bp). Για την επίκτητη ανοσία μελετήθηκαν δύο πολυμορφισμοί του BAFF-R (BAFF-R-H159Y και BAFF-R-P21R) και ένας του TACI (TACI-C104R). Η ανίχνευση των πολυμορφισμών έγινε με αλυσιδωτή αντίδραση πολυμεράσης και ανάλυση με ενδονουκλεάσες περιορισμού (PCR-RFLP). Αποτελέσματα: Στη μελέτη συμπεριελήφθησαν 215 ασθενείς (148 άνδρες και 67 γυναίκες). Η ηλικία (μέσος ± SD) ήταν 54,1±19,7 έτη, APACHE II score εισαγωγής στη ΜΕΘ 22,0±6,0 και SOFA score εισαγωγής στη ΜΕΘ 9,7±3,5. Σήψη στη ΜΕΘ βρέθηκε σε 108 ασθενείς (50,2%) και η θνητότητα στη ΜΕΘ ήταν 20,5% [95% διάστημα αξιοπιστίας 15,0–25,9]. Οι SNPs του TLR4 βρέθηκαν σε συζευγμένη κατάσταση. Οι φορείς κάποιου TLR4 SNP και οι φορείς του BAFFR-P21R συσχετίστηκαν ανεξάρτητα με χαμηλότερη πιθανότητα σήψης στη ΜΕΘ συγκριτικά με τους wild-type ομοζυγώτες [διορθωμένα odds ratios 0,32, 95%CI 0,12–0,86, p=0,024 για τον TLR4-T399I, 0,34, 95%CI 0,13–0,94, p=0,037 για τον TLR4-T399I and 0,44, 95%CI 0,20–0,97, p=0,044 για τον BAFFR-P21R]. Από την ανάλυση υποομάδων, φάνηκε ότι η συσχέτιση αυτή αφορούσε στους παθολογικούς ασθενείς και οριακά στους τραυματίες, ενώ στους χειρουργικούς ασθενείς δεν παρατηρήθηκε συσχέτιση. Η φορεία του TACI-C104R SNP είχε καλή προβλεπτική αξία μετά από διόρθωση ως προς συγχυτικούς παράγοντες [hazard ratio 5,01 (1,14–22,03, p=0,033). Ο BAFFR-H159Y SNP δεν συσχετίστηκε με την εμφάνιση σήψης και τη θνητότητα, ενώ ο πολυμορφισμός C2del28bp δεν ανευρέθηκε στο δείγμα της μελέτης.Συμπεράσματα: Η μελέτη μας έδειξε ότι σε βαρέως πάσχοντες ασθενείς ΜΕΘ, οι πολυμορφισμοί TLR4-D299G (rs4986790), TLR4-T399I (rs4986791) και TNFRSF13C/BAFFR-P21R (rs77874543) ασκούν προστατευτική επίδραση αναφορικά με την εμφάνιση σήψης, ενώ ο πολυμορφισμός TNFRSF13B/TACI-C104R (rs34557412) συσχετίζεται σημαντικά με αύξηση της θνητότητας στη ΜΕΘ. Ο πολυμορφισμός TNFRSF13C/BAFFR-H159Y (rs61756766) δεν συσχετίστηκε με την εμφάνιση σήψης ή τη θνητότητα στη ΜΕΘ. Διαπιστώθηκε ανισορροπία σύνδεσης για τους πολυμορφισμούς TLR4-D299G (rs4986790) και TLR4-T399I (rs4986791) και για τους πολυμορφισμούς TNFRSF13C/BAFFR-P21R (rs77874543) και TNFRSF13C/BAFFR-H159Y (rs61756766). Ο πολυμορφισμός C2-c.841_849+19del28 (rs9332736) δεν ανιχνεύτηκε στο δείγμα των ασθενών της μελέτης

Weaning Failure in Critically Ill Patients Is Related to the Persistence of Sepsis Inflammation

Introduction: Septic patients undergoing mechanical ventilation (MV) often experience difficulty in weaning. Th aim of this study was to determine whether inflammatory biomarkers of sepsis could be indicative of the failure or success of spontaneous breathing trial (SBT) in these patients. Methods: Sixty-five patients on MV (42 septic and 23 intubated for other reasons) fulfilling the criteria for SBT were included in the study. Blood samples were collected right before, at the end of (30 min) and 24 h after the SBT. Serum inflammatory mediators associated with sepsis (IL-18, IL-18BP, TNF) were determined and correlated with the outcome of SBT. Results: A successful SBT was achieved in 45 patients (69.2%). Septic patients had a higher percentage of SBT failure as compared to non-septic patients (85% vs. 15%, p = 0.026), with an odds ratio for failing 4.5 times (OR = 4.5 95%CI: 1.16&ndash;17.68, p 0.022). IL-18 levels and the relative mRNA expression in serum were significantly higher in septic as compared to non-septic patients (p &lt; 0.05). Sepsis was independently associated with higher serum IL-18 and TNF levels in two time-point GEE models (53&ndash;723, p = 0.023 and 0.3&ndash;64, p = 0.048, respectively). IL-18BP displayed independent negative association with rapid shallow breathing index (RSBI) (95% CI: &minus;17.6 to &minus;4, p = 0.002). Conclusion: Sustained increased levels of IL-18 and IL-18BP, acknowledged markers of sepsis, were found to be indicative of SBT failure in patients recovering from sepsis. Our results show that, although subclinical, remaining septic inflammation that sustaines for a long time complicates the weaning procedure. Biomarkers for the estimation of the septic burden and the right time for weaning are needed

Weaning Failure in Critically Ill Patients Is Related to the Persistence of Sepsis Inflammation

Introduction: Septic patients undergoing mechanical ventilation (MV) often experience difficulty in weaning. Th aim of this study was to determine whether inflammatory biomarkers of sepsis could be indicative of the failure or success of spontaneous breathing trial (SBT) in these patients. Methods: Sixty-five patients on MV (42 septic and 23 intubated for other reasons) fulfilling the criteria for SBT were included in the study. Blood samples were collected right before, at the end of (30 min) and 24 h after the SBT. Serum inflammatory mediators associated with sepsis (IL-18, IL-18BP, TNF) were determined and correlated with the outcome of SBT. Results: A successful SBT was achieved in 45 patients (69.2%). Septic patients had a higher percentage of SBT failure as compared to non-septic patients (85% vs. 15%, p = 0.026), with an odds ratio for failing 4.5 times (OR = 4.5 95%CI: 1.16-17.68, p 0.022). IL-18 levels and the relative mRNA expression in serum were significantly higher in septic as compared to non-septic patients (p &lt; 0.05). Sepsis was independently associated with higher serum IL-18 and TNF levels in two time-point GEE models (53-723, p = 0.023 and 0.3-64, p = 0.048, respectively). IL-18BP displayed independent negative association with rapid shallow breathing index (RSBI) (95% CI: -17.6 to -4, p = 0.002). Conclusion: Sustained increased levels of IL-18 and IL-18BP, acknowledged markers of sepsis, were found to be indicative of SBT failure in patients recovering from sepsis. Our results show that, although subclinical, remaining septic inflammation that sustaines for a long time complicates the weaning procedure. Biomarkers for the estimation of the septic burden and the right time for weaning are needed

Searching for genetic biomarkers for hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE)

Existing evidence indicates that modifier genes could change the phenotypic outcome of the causal SERPING1 variant and thus explain the expression variability of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE). To further examine this hypothesis, we investigated the presence or absence of 18 functional variants of genes encoding proteins involved in the metabolism and function of bradykinin, the main mediator of C1-INH-HAE attacks, in relation to three distinct phenotypic traits of patients with C1-INH-HAE, i.e., the age at disease onset, the need for long-term prophylaxis (LTP), and the severity of the disease. Genetic analyses were performed by a validated next-generation sequencing platform. In total, 233 patients with C1-INH-HAE from 144 unrelated families from five European countries were enrolled in the study. Already described correlations between five common functional variants [F12-rs1801020, KLKB1-rs3733402, CPN1-rs61751507, and two in SERPING1 (rs4926 and rs28362944)] and C1-INH-HAE severity were confirmed. Furthermore, significant correlations were found between either the age at disease onset, the LTP, or the severity score of the disease and a series of other functional variants (F13B-rs6003, PLAU-rs2227564, SERPINA1-rs28929474, SERPINA1-rs17580, KLK1-rs5515, SERPINE1-rs6092, and F2-rs1799963). Interestingly, correlations uncovered in the entire cohort of patients were different from those discovered in the cohort of patients carrying missense causal SERPING1 variants. Our findings indicate that variants other than the SERPING1 causal variants act as independent modifiers of C1-INH-HAE severity and could be tested as possible prognostic biomarkers

Tigecycline in the treatment of infections from multi-drug resistant gram-negative pathogens

Objective: This observational retrospective study aims to present early experience with tigecycline (TIG) in the treatment of infections due to multi-drug resistant (MDR) microorganisms. Methods: Adult patients included, received TIG for &gt;5 days either as monotherapy (M group) or as presumed active monotherapy (PAM group). In the PAM group, all co-administered antimicrobial(s) were resistant in vitro against the targeted pathogen(s) or had been clinically and microbiologically failing after &gt;5 days of therapy despite in vitro susceptibility. Results: Forty-five patients (35 in ICU) were treated for 28 Acinetobacter baumannii and 23 Klebsiella pneumoniae infections [21 ventilator-associated and healthcare-acquired pneumonia (VAP/HCAP), 10 bloodstream infections (BSI) and 14 surgical infections (SI)]. Successful overall clinical outcome was 80%, i.e. 81.8% in M group, 78.3% in PAM group, 90.5% in VAP/HCAP, 80% in BSI, 64.3% in SI and 85% in the cases with septic shock. Superinfections from Enterobacteriaceae inherently resistant to tigecycline occurred in 31.8% of M and 13% of PAM group (p&lt;0.001). Conclusion: TIG represents a promising option in infections from MDR pathogens, however, further clinical experience is required. (c) 2009 The British Infection Society. Published by Elsevier Ltd. All rights reserved