Terapia nadczynności tarczycy jodem promieniotwórczym jest bezpieczna u chorych na chorobę Gravesa i Basedowa z orbitopatią — badanie prospektywne

Introduction: Radioactive iodine (RAI) therapy may induce or worsen orbitopathy (GO) in Graves’ disease (GD). The aim of this study was a prospective assessment of the risk of GO exacerbation in a GD patients cohort submitted to RAI therapy for hyperthyroidism.Material and methods: 208 consecutive GD patients treated with 131I in 2007 were enrolled. The analysis was performed on 156 patients strictly monitored for one year. Glucocorticosteroid (GCS) prophylaxis was administered if GO symptoms or GO history were present, and in cases of tobacco smokers even without GO symptoms. Clinical and biochemical evaluation at one, three, six, and 12 months after therapy was performed in the whole group, then at 24 months in 138 patients.Results: There was no severe GO progression in patients without GO symptoms at the time of RAI treatment. The risk of severe GO worsening for preexisting GO patients (demanding systemic GCS administration) during the 12-month follow-up after RAI therapy was 10%. 12 and 24 months after 131I administration, stable improvement compared to the initial GO status had been achieved in most (98–96%) patients.Conclusions:1. In patients with mild GO, the risk of severe GO worsening after RAI therapy is acceptable, as long as RAI therapy is applied with GCS cover.2. In patients without GO symptoms at the time of RAI therapy but with a history of GO and with subclinical GO diagnosed by MRI only, the risk of severe progression is minimal.3. Distant outcomes of RAI treatment confirmed its safety in GO patients. (Endokrynol Pol 2014; 65 (1): 40–45)Wstęp: Leczenie jodem promieniotwórczym (131I) może indukować lub nasilać objawy orbitopatii u pacjentów z rozpoznaniem choroby Graves-Basedowa (CHGB). Celem pracy była prospektywna ocena ryzyka zaostrzenia orbitopatii w grupie chorych leczonych 131I z powodu nadczynności tarczycy.Materiał i metody: Do badania włączono 208 kolejnych pacjentów z rozpoznaniem CHGB leczonych 131I w 2007. Do analizy włączono 156 chorych ściśle monitorowanych przez rok. Osłona glikokortykoidowa (GCS) była stosowana w przypadku występowania objawów orbitopatii, dodatniego wywiadu w kierunku orbitopatii i u palaczy tytoniu, także bez objawów orbitopatii. Kliniczna i biochemiczna ocena była przeprowadzona w całej grupie 1, 3, 6 i 12 miesięcy po leczeniu 131I i u 138 chorych po 24 miesiącach.Wyniki: Nie obserwowano poważnego zaostrzenia orbitopatii u chorych bez objawów GO w chwili leczenia 131I. Ryzyko istotnej progresji orbitopatii (wymagającej stosowania GKS systemowych) w ciągu 12 miesięcznej obserwacji wynosiło u chorych z wyjściowymi objawami orbitopatii 10%. U większości chorych 12 i 24 miesiące po leczeniu 131I poprawa orbitopatii w porównaniu ze stanem wyjściowym była trwała.Wnioski:1. Ryzyko istotnej progresji objawów po leczeniu 131I u chorych z orbitopatią o umiarkowanym nasileniu jest akceptowalne.2. Ryzyko progresji orbitopatii u chorych bez objawów w chwili leczenia 131I, ale z dodatnim wywiadem w kierunku orbitopatii i z subklinicznymi objawami (obecnymi tylko w badaniu NMR) jest minimalne.3. Odległa ocena potwierdza bezpieczeństwo terapii radiojodem u chorych z orbitopatią. (Endokrynol Pol 2014; 65 (1): 40–45

Predictors for prolonged hospital stay solely to complete intravenous antifungal treatment in patients with candidemia: Results from the ECMM candida III multinational European observational cohort study

Background To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates of azole resistance among non-albicans Candida spp. continue to increase. The objective of this sub-analysis of the European multicenter observational cohort study Candida III was to describe demographical and clinical characteristics of the cohort requiring prolonged hospitalization solely to complete intravenous (iv) antifungal treatment (AF Tx). Methods Each participating hospital (number of eligible hospitals per country determined by population size) included the first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, and treating physicians answered the question on whether hospital stay was prolonged only for completion of intravenous antifungal therapy. Descriptive analyses as well as binary logistic regression was used to assess for predictors of prolonged hospitalization solely to complete iv AF Tx. Findings Hospital stay was prolonged solely for the completion of iv AF Tx in 16% (100/621) of candidemia cases by a median of 16 days (IQR 8 – 28). In the multivariable model, initial echinocandin treatment was a positive predictor for prolonged hospitalization to complete iv AF Tx (aOR 2.87, 95% CI 1.55 – 5.32, p < 0.001), while (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, (iv) total parenteral nutrition, and (v) C. parapsilosis as causative pathogen were found to be negative predictors (aOR 0.22 – 0.45; p < 0.03). Interpretation Hospital stays were prolonged due to need of iv AF Tx in 16% of patients with candidemia. Those patients were more likely to receive echinocandins as initial treatment and were less severely ill and less likely infected with C. parapsilosis

Novel Genome-Wide Association Study-Based Candidate Loci for Differentiated Thyroid Cancer Risk

Context: Genome-wide association studies (GWASs) on differentiated thyroid cancer (DTC) have identified robust associations with single nucleotide polymorphisms (SNPs) at 9q22.33 (FOXE1), 14q13.3 (NKX2-1), and 2q35 (DIRC3). Our recently published GWAS suggested additional susceptibility loci specific for the high-incidence Italian population. Objective: The purpose of this study was to identify novel Italian-specific DTC risk variants based on our GWAS and to test them further in low-incidence populations. Design: We investigated 45 SNPs selected from our GWAS first in an Italian population. SNPs that showed suggestive evidence of association were investigated in the Polish and Spanish cohorts. Results: The combined analysis of the GWAS and the Italian replication study (2260 case patients and 2218 control subjects) provided strong evidence of association with rs10136427 near BATF (odds ratio [ OR] = 1.40, P = 4.35 x 10(-7)) and rs7267944 near DHX35 (OR = 1.39, P = 2.13 x 10(-8)). A possible role in DTC susceptibility in the Italian populations was also found for rs13184587 (ARSB) (P = 8.54 x 10(-6)) and rs1220597 (SPATA13) (P = 3.25 x 10(-6)). Only the associations between rs10136427 and rs7267944 and DTC risk were replicated in the Polish and the Spanish populations with little evidence of population heterogeneity (GWAS and all replications combined, OR = 1.30, P = 9.30 x 10(-7) and OR = 1.32, P = 1.34 x 10(-8), respectively). In silico analyses provided new insights into the possible functional consequences of the SNPs that showed the strongest association with DTC. Conclusions: Our findings provide evidence for novel DTC susceptibility variants. Further studies are warranted to identify the specific genetic variants responsible for the observed associations and to functionally validate our in silico predictions

Kinetic models of swelling and thermal stability of silver/poly(vinyl alcohol)/chitosan/graphene hydrogels

Silver nanoparticles (AgNPs) were synthesized by in situ electrochemical reduction of Ag+ ions in poly(vinyl alcohol)/chitosan/graphene (PVA/CHI/Gr) hydrogel matrices with different concentrations of chitosan. The physicochemical properties of nanocomposite hydrogels were investigated by UV–vis spectroscopy (UV–vis), dynamic light scattering (DLS), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM) and Fourier-transform infrared spectroscopy (FT-IR), thermal characteristics were determined by differential scanning calorimetry (DSC) and mechanical properties were measured by tensile test. The swelling studies were carried out in phosphate buffer to simulate natural physiological environment and data were fitted by several kinetic models to determine the diffusion mechanism and diffusion coefficients of the swelling medium through the hydrogel matrices. It was shown that the presence of silver nanoparticles increased the uptake capability and equilibrium swelling degree of the composite hydrogels. The antibacterial activity was confirmed against Escherichia coli and Staphylococcus aureus, while the hydrogels without AgNPs exhibited antibacterial properties due to the presence of chitosan. With the addition of AgNPs, the samples showed stronger activity and fast reduction in the number of colonies, confirming the synergistic effect of chitosan and AgNPs on the antibacterial activity.Published version [http://technorep.tmf.bg.ac.rs/handle/123456789/4239]This is the peer-reviewed version of the following article: Nešović K, Janković A, Perić-Grujić A, Vukašinović-Sekulić M, Radetić T, Živković L, Park SJ, Rhee KY, Mišković-Stanković V. Kinetic models of swelling and thermal stability of silver/poly(vinyl Check far alcohol)/chitosan/graphene hydrogels. in Journal of Industrial and Engineering Chemistry. 2019;77:83-96. [doi:10.1016/j.jiec.2019.04.022

Conserved and Novel Functions for Arabidopsis thaliana MIA40 in Assembly of Proteins in Mitochondria and Peroxisomes

The disulfide relay system of the mitochondrial intermembrane space has been extensively characterized in Saccharomyces cerevisiae. It contains two essential components, Mia40 and Erv1. The genome of Arabidopsis thaliana contains a single gene for each of these components. Although insertional inactivation of Erv1 leads to a lethal phenotype, inactivation of Mia40 results in no detectable deleterious phenotype. A. thaliana Mia40 is targeted to and accumulates in mitochondria and peroxisomes. Inactivation of Mia40 results in an alteration of several proteins in mitochondria, an absence of copper/zinc superoxide dismutase (CSD1), the chaperone for superoxide dismutase (Ccs1) that inserts copper into CSD1, and a decrease in capacity and amount of complex I. In peroxisomes the absence of Mia40 leads to an absence of CSD3 and a decrease in abnormal inflorescence meristem 1 (Aim1), a β-oxidation pathway enzyme. Inactivation of Mia40 leads to an alteration of the transcriptome of A. thaliana, with genes encoding peroxisomal proteins, redox functions, and biotic stress significantly changing in abundance. Thus, the mechanistic operation of the mitochondrial disulfide relay system is different in A. thaliana compared with other systems, and Mia40 has taken on new roles in peroxisomes and mitochondria

Guideline adherence and survival of patients with candidaemia in Europe: results from the ECMM Candida III multinational European observational cohort study

Background: The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes. Methods: In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines. Findings: 632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1·08 [95% CI 1·04-1·11; p&lt;0·0001] in patients with a central venous catheter and 1·09 [1·05-1·13; p&lt;0·0001] in those without one, per one score point decrease). Median duration of hospital stay was 15 days (IQR 4-30) after diagnosis of candidaemia and was extended specifically for completion of parenteral therapy in 100 (16%) of 621 patients. Initial echinocandin treatment was associated with lower overall mortality and longer duration of hospital stay among survivors than treatment with other antifungals. Interpretation: Although overall mortality in patients with candidaemia was high, our study indicates that adherence to clinical guideline recommendations, reflected by higher EQUAL Candida scores, might increase survival. New antifungals, with similar activity as current echinocandins but with longer half-lives or oral bioavailability, are needed to reduce duration of hospital stay. Funding: Scynexis

Matched-paired analysis of patients treated for invasive mucormycosis: standard treatment versus posaconazole new formulations (MoveOn)

International audienceBackground : First-line antifungal treatment for invasive mucormycosis (IM) consists of liposomal amphotericin B. Salvage treatment options are limited and often based on posaconazole oral suspension. With the approval of posaconazole new formulations, patients could benefit from improved pharmacokinetics, safety and tolerability.Objectives: Our aim was to assess the effectiveness of posaconazole new formulations for IM treatment.Methods : We performed a case-matched analysis with proven or probable IM patients from the FungiScope® Registry. First-line posaconazole new formulations (1st-POSnew) and first-line amphotericin B plus posaconazole new formulations (1st-AMB+POSnew) cases were matched with first-line amphotericin B-based (1st-AMB) treatment controls. Salvage posaconazole new formulations (SAL-POSnew) cases were matched with salvage posaconazole oral suspension (SAL-POSsusp) controls. Each case was matched with up to three controls (based on severity, haematological/oncological malignancy, surgery and/or renal dysfunction).Results : Five patients receiving 1st-POSnew, 18 receiving 1st-AMB+POSnew and 22 receiving SAL-POSnew were identified. By day 42, a favourable response was reported for 80.0% (n = 4/5) of patients receiving 1st-POSnew, for 27.8% (n = 5/18) receiving 1st-AMB+POSnew and for 50.0% (n = 11/22) receiving SAL-POSnew. Day 42 all-cause mortality of patients receiving posaconazole new formulations was lower compared with controls [20.0% (n = 1/5) in 1st-POSnew versus 53.3% (n = 8/15) in 1st-AMB; 33.3% (n = 6/18) in 1st-AMB+POSnew versus 52.0% (n = 26/50) in 1st-AMB; and 0.0% (n = 0/22) in SAL-POSnew versus 4.4% (n = 2/45) in SAL-POSsusp].Conclusions : Posaconazole new formulations were effective in terms of treatment response and associated mortality of IM. While posaconazole new formulations may be an alternative for treatment of IM, the limited sample size of our study calls for a cautious interpretation of these observations

Needles in a haystack: Extremely rare invasive fungal infections reported in FungiScopeⓇ—Global Registry for Emerging Fungal Infections

International audienc