Can absolute arterial phase hyperenhancement improve sensitivity of detection of hepatocellular carcinoma in indeterminate nodules on CT?

OBJECTIVES: To determine if quantitative assessment of relative (R) and absolute (A) arterial phase hyperenhancement (APHE) and washout (WO) applied to indeterminate nodules on CT would improve the overall sensitivity of detection of hepatocellular carcinoma (HCC). METHODS: One-hundred and fourteen patients (90 male; mean age, 65 years) with 210 treatment-naïve HCC nodules (190 HCCs, 20 benign) who underwent 4-phase CT were included in this retrospective study. Four radiologists independently assigned a qualitative LR (LI-RADS) category per nodule. LR-3/4 nodules were then quantitatively analyzed by the 4 readers, placing ROIs within nodules and adjacent liver parenchyma. A/R-APHE and WO were calculated, and per-reader sensitivity and specificity updated. Interobserver agreement and AUCs were calculated per reader. RESULTS: Qualitative readers 1-4 categorized 57, 69, 57, and 63 nodules as LR-3/4 respectively with moderate to substantial agreement in LR category (kappa 0.56-0.69, p < 0.0001); their diagnostic performances in the detection of HCC were 80%, 73.2%, 77.4%, and 77.4% sensitivity, and 100%, 95%, 70%, and 100% specificity, respectively. A threshold of ≥ 20 HU for A-APHE increased overall sensitivity of HCC detection by 0.5-3.1% without changing specificity for the subset of nodules APHE - /WO + on qualitative read, with 2, 6, 6, and 1 additional HCC detected by readers 1-4. Relative and various A-WO formulae and thresholds all increased sensitivity, but with a drop in specificity for some/all readers. CONCLUSION: Quantitatively assessed A-APHE showed potential to increase sensitivity and maintain specificity of HCC diagnosis when selectively applied to indeterminate nodules demonstrating WO without subjective APHE. Quantitatively assessed R and A-WO increased sensitivity, however reduced specificity. CLINICAL RELEVANCE STATEMENT: A workflow using selective quantification of absolute arterial enhancement is routinely employed in the CT assessment of renal and adrenal nodules. Quantitatively assessed absolute arterial enhancement is a simple tool which may be used as an adjunct to help increase sensitivity and maintain specificity of HCC diagnosis in indeterminate nodules demonstrating WO without subjective APHE. KEY POINTS: • In indeterminate nodules categorized as LI-RADS 3/4 due to absent subjective arterial phase hyperenhancement, a cut-off for absolute arterial phase hyperenhancement of ≥ 20 HU may increase the overall sensitivity of detection of HCC by 0.5-3.1% without affecting specificity. • Relative and various absolute washout formulae and cut-offs increased sensitivity of HCC detection, but with a drop in specificity for some/all readers.

COVID-19: What if immunity wanes?

Using a simple economic model in which social distancing reduces contagion, we study the implications of waning immunity for the epidemiological dynamics and social activity. If immunity wanes, we find that COVID-19 likely becomes endemic and that social distancing is here to stay until the discovery of a vaccine or cure. But waning immunity does not necessarily change optimal actions on the onset of the pandemic. Decentralized equilibria are virtually independent of waning immunity until close to peak infections. For centralized equilibria, the relevance of waning immunity decreases in the probability of finding a vaccine or cure, the costs of infection (e.g., infection-fatality rate), the degree of partial immunity and the presence of other NPIs that lower contagion (e.g., quarantining and mask use). In simulations calibrated to July 2020, our model suggests that waning immunity is virtually unimportant for centralized equilibria until at least 2021. This provides vital time for individuals and policy-makers to learn about immunity against SARS-CoV-2 before it becomes critical.

COVID­19 : et si l'immunité diminuait? À l'aide d'un modèle économique simple dans lequel la distanciation sociale permet de réduire la contagion, nous analysons les conséquences d'une baisse de l'immunité sur les dynamiques épidémiologiques et les activités sociales. Nous constatons que si l'immunité décline, c'est que la COVID­19 devient vraisemblablement endémique et que la distanciation sociale est vouée à perdurer jusqu'à la découverte d'un remède ou d'un vaccin. Néanmoins, une diminution de l'immunité ne modifie pas nécessairement les mesures optimales à prendre dès le début de la pandémie. Les équilibres décentralisés sont théoriquement indépendants d'une baisse de l'immunité jusqu'à l'approche du pic d'infection. Pour les équilibres centralisés, l'importance d'une diminution de l'immunité décroît avec la probabilité de trouver un vaccin ou un remède, avec les coûts imputables à l'infection (par exemple le taux de létalité), avec le taux d'immunité partielle et en présence d'autres interventions non pharmaceutiques (INP) permettant de diminuer la contagion (mises en quarantaine et utilisation du masque notamment). Dans les simulations calibrées sur juillet 2020, notre modèle montre qu'une baisse de l'immunité est pratiquement sans importance sur les équilibres centralisés, et ce au moins jusqu'en 2021. Cette période cruciale permettra aux individus et aux législateurs d'en apprendre davantage sur l'immunité contre le SARS­CoV­2 avant que le virus ne devienne critique.

Proteins from the core genome of Corynebacterium ulcerans respond for pathogenicity and reveal promising vaccine targets for diphtheria.

Corynebacterium ulcerans is an emerging pathogen able to transmit the acute infection diphtheria to humans. Although there is a well-established vaccine based on the toxin produced by Corynebacterium diphtheriae, another species of this genus known to cause the disease, there is still no vaccine formulations described for C. ulcerans; this fact contributes to the increase in cases of infection that has been observed. In this study, we want to provide information at the genomic level of this bacterium in order to suggest proteins as possible vaccine targets. We carried out an in silico prospection of vaccine candidates through reverse vaccinology for targets that exhibit antigenic potential against diphtheria. We found important virulence factors, such as adhesion-related ones, that are responsible for pathogen-host interaction after infection, but we did not find the diphtheria toxin, which is the main component of the currently available vaccine. This study provides detailed information about the exoproteome and hypothetical proteins from the core genome of C. ulcerans, suggesting vaccine targets to be further tested in vitro for the development of a new vaccine against diphtheria.

The added value of contrast-enhanced ultrasound in evaluation of indeterminate small solid renal masses and risk stratification of cystic renal lesions.

OBJECTIVES: To investigate accuracy of contrast-enhanced ultrasound (CEUS) to characterize indeterminate small solid renal masses (sSRMs), excluding lipid-rich AMLs, and cystic renal masses (CRMs) according to the proposed Bosniak Classification 2019 MATERIALS AND METHODS: CEUS of pathology-proven CRMs and sSRMs (without definite enhancement or macroscopic fat on CT/MRI), and CRMs with ≥18 months follow-up were retrospectively reviewed. Two radiologists blindly categorized CRMs according to new Bosniak Classification on CT/MRI. On CEUS, two other radiologists evaluated arterial-phase enhancement of sSRMs relative to renal cortex and categorized CRMs following new Bosniak Classification. Fisher's exact/chi-squared test was used to compare categorical variables, and Cohen κ statistics for inter-observer agreement RESULTS: A total of 237 patients had 241 lesions: 161 pathology-proven sSRMs (122 malignant and 39 benign), 29 pathology-proven CRMs, 51 CRMs with adequate follow-up. Arterial-phase enhancement < renal cortex predicted malignancy with specificity of 97.4% (38/39) (CI 85.6-99.9%), and positive predictive value (PPV) of 98.2% (54/55) (CI 90.4-99.9%). Inter-observer kappa was 0.95. In pathology-proven CRMS, sensitivity of CEUS vs CT/MRI was 100% (15/15) (CI 79.6-100%) vs 60% (9/15) (CI 35.8-80.1%) (p value = .002) and negative predictive value (NPV) 100% (2/2) (CI 17.8-100%) vs 25% (2/8 ) (CI 4.4-59.1%) (p value < 0.0001), with similar specificity (50%) and PPV- 88.2% (15/17) (CI 65.7-97.9%) vs 81.8% (9/11) (CI 52.3-96.8%) ( p value = 0.586). Bosniak Classification inter-observer kappa was 0.92 for CEUS vs 0.68 for CT/MRI (p value = 0.009). CONCLUSION: In our cohort, CEUS had high specificity and PPV to diagnose RCC in sSRMs excluding lipid-rich AML. CEUS had significantly higher sensitivity/NPV to diagnose malignancy in CRMs as compared to CT/MRI. KEY POINTS: • Once lipid-rich AML is excluded by the other modalities, sSRM arterial phase hypo-enhancement relative to renal cortex on CEUS yielded high specificity (97.4%) and PPV (98.2%) to diagnose RCC. • When applying the proposed Bosniak Classification 2019, CEUS showed higher sensitivity compared to CT/MRI (100% vs 60%), p value=.0024, in the stratification of cystic renal masses to diagnose malignancy. • CEUS may reduce the number of CT/MRI Bosniak IIF lesions by assigning them to either II or III/IV categories.

Evaluation of Crohn Disease Activity Using a Potential Abbreviated MRE Protocol Consisting of Balanced Steady-State Free Precession MRI Only Versus Full-Protocol MRE.

OBJECTIVE. The purpose of the present study was to compare the diagnostic performance of an abbreviated MR enterography (MRE) protocol consisting of balanced steady-state free-precession (b-SSFP) imaging only versus standard full-protocol MRE for the evaluation of Crohn disease activity. MATERIALS AND METHODS. This single-center retrospective study included 112 patients with Crohn disease (66 women and 46 men; age range, 18-84 years) who underwent MRE between January 2017 and March 2018. Utilizing binary and 5-point Likert confidence scales, two blinded readers independently interpreted and scored disease activity on b-SSFP sequences only and on full-protocol MRE images. Interreader and intrareader agreement on confidence regarding disease activity were calculated using weighted kappa indexes. Correlation between MRE findings of Crohn disease and the Harvey-Bradshaw index was also performed. RESULTS. Perfect intrareader agreement and strong interreader agreement on disease activity were observed (intrareader agreement: κ = 0.97, 0.96, and 0.96 for reader A, reader B, and both readers combined; interreader agreement: κ = 0.82 for b-SSFP imaging only and κ = 0.81 for MRE). For detecting active Crohn disease, b-SSFP sequences had a sensitivity and specificity of 97% and 100%, respectively, for reader A and 98% and 86%, respectively, for reader B. Strong-to-perfect intrareader agreement was achieved between b-SSFP imaging only and MRE for identification of penetrating disease (κ = 0.80 and 0.97) and stenosing disease (κ = 0.87 and 0.95). Perfect intrareader agreement was also obtained between b-SSFP imaging only and MRE for detecting abnormal bowel segments (κ = 0.91 for reader A; κ = 0.98 for reader B). Weak agreement was noted between both b-SSFP imaging only and MRE versus the Harvey-Bradshaw index (κ = 0.08 of reader A; κ = 0.04 for reader B). CONCLUSION. Robust agreement was observed between b-SSFP imaging only and full-protocol MRE for the assessment of Crohn disease activity and complications. An abbreviated MRE protocol that exclusively uses b-SSFP sequences appears feasible and has significant implications for health care resources.

CT Noise-Reduction Methods for Lower-Dose Scanning: Strengths and Weaknesses of Iterative Reconstruction Algorithms and New Techniques.

Iterative reconstruction (IR) algorithms are the most widely used CT noise-reduction method to improve image quality and have greatly facilitated radiation dose reduction within the radiology community. Various IR methods have different strengths and limitations. Because IR algorithms are typically nonlinear, they can modify spatial resolution and image noise texture in different regions of the CT image; hence traditional image-quality metrics are not appropriate to assess the ability of IR to preserve diagnostic accuracy, especially for low-contrast diagnostic tasks. In this review, the authors highlight emerging IR algorithms and CT noise-reduction techniques and summarize how these techniques can be evaluated to help determine the appropriate radiation dose levels for different diagnostic tasks in CT. In addition to advanced IR techniques, we describe novel CT noise-reduction methods based on convolutional neural networks (CNNs). CNN-based noise-reduction techniques may offer the ability to reduce image noise while maintaining high levels of image detail but may have unique drawbacks. Other novel CT noise-reduction methods are being developed to leverage spatial and/or spectral redundancy in multiphase or multienergy CT. Radiologists and medical physicists should be familiar with these different alternatives to adapt available CT technology for different diagnostic tasks. The scope of this article is (a) to review the clinical applications of IR algorithms as well as their strengths, weaknesses, and methods of assessment and (b) to explore new CT image reconstruction and noise-reduction techniques that promise to facilitate radiation dose reduction. ©RSNA, 2021.

Antibody tests: They are more important than we thought.

Antibody testing is a non-pharmaceutical intervention - not recognized so far in the literature - to prevent COVID-19 contagion. I show this in a simple economic model of an epidemic in which agents choose social activity under health state uncertainty. In the model, susceptible and asymptomatic agents are more socially active when they think they might be immune. And this increased activity escalates infections, deaths, and welfare losses. Antibody testing, however, prevents this escalation by revealing that those agents are not immune. Through this mechanism, I find that antibody testing prevents about 12% of COVID-19 related deaths within 12 months.

The small molecule AZD6244 inhibits dengue virus replication in vitro and protects against lethal challenge in a mouse model.

Dengue virus (DENV) is the most common mosquito-borne viral disease. The World Health Organization estimates that 400 million new cases of dengue fever occur every year. Approximately 500,000 individuals develop severe and life-threatening complications from dengue fever, such as dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF), which cause 22,000 deaths yearly. Currently, there are no specific licensed therapeutics to treat DENV illness. We have previously shown that the MEK/ERK inhibitor U0126 inhibits the replication of the flavivirus yellow fever virus. In this study, we demonstrate that the MEK/ERK inhibitor AZD6244 has potent antiviral efficacy in vitro against DENV-2, DENV-3, and Saint Louis encephalitis virus (SLEV). We also show that it is able to protect AG129 mice from a lethal challenge with DENV-2 (D2S20). The molecule is currently undergoing phase III clinical trials for the treatment of non-small-cell lung cancer. The effect of AZD6244 on the DENV life cycle was attributed to a blockade of morphogenesis. Treatment of AG129 mice twice daily with oral doses of AZD6244 (100 mg/kg/day) prevented the animals from contracting dengue hemorrhagic fever (DHF)-like lethal disease upon intravenous infection with 1 × 105 PFU of D2S20. The effectiveness of AZD6244 was observed even when the treatment of infected animals was initiated 1-2 days postinfection. This was also followed by a reduction in viral copy number in both the serum and the spleen. There was also an increase in IL-1ß and TNF-α levels in mice that were infected with D2S20 and treated with AZD6244 in comparison to infected mice that were treated with the vehicle only. These data demonstrate the potential of AZD6244 as a new therapeutic agent to treat DENV infection and possibly other flavivirus diseases.

State of the Art in Abdominal CT: The Limits of Iterative Reconstruction Algorithms.

The development and widespread adoption of iterative reconstruction (IR) algorithms for CT have greatly facilitated the contemporary practice of radiation dose reduction during abdominal CT examinations. IR mitigates the increased image noise typically associated with reduced radiation dose levels, thereby maintaining subjective image quality and diagnostic confidence for a variety of clinical tasks. Mounting evidence, however, points to important limitations of this method involving radiologists' ability to perform low-contrast diagnostic tasks, such as the detection of liver metastases or pancreatic masses. Radiologists need to be aware that use of IR can result in a decline of spatial resolution for low-contrast structures and degradation of low-contrast detectability when radiation dose reductions exceed approximately 25%. This article will review the principles of IR algorithm technology, describe the various commercial implementations of IR in CT, and review published studies that have evaluated the ability of IR to preserve diagnostic performance for low-contrast diagnostic tasks. In addition, future developments in CT noise reduction techniques and methods to rigorously evaluate their diagnostic performance will be discussed.

Different strategies to kill the host presented by Metarhizium anisopliae and Beauveria bassiana.

Studies conducted over the last decades have shown the potential of entomopathogenic fungi for the biocontrol of some insect pests. Entomopathogenic fungi infect their host through the cuticle, so they do not need to be ingested to be effective. These fungi also secrete secondary metabolites and proteins that are toxic to insect pests. In this context, we analyzed the pathogenicity of Metarhizium anisopliae (Metschn.) strains IBCB 384 and IBCB 425 and Beauveria bassiana (Bals.-Criv.) Vuill. strains E 1764 and E 3158 against Galleria mellonella (Linn.) larvae, during pre-invasion and post-invasion phases. The results showed M. anisopliae, especially strain IBCB 384, was most virulent in the pre-invasion phase against G. mellonella, whereas B. bassiana, especially strain E 1764, was most virulent in the post-invasion phase. During in vivo development and in the production of toxic serum, B. bassiana E 3158 was the most virulent. Different fungal growth (or toxin) strategies were observed for studied strains. Metarhizium anisopliae IBCB 425 prioritizes the growth strategy, whereas strain IBCB 384 and B. bassiana strains E 1764 and E 3158 have a toxic strategy. All strains have pathogenicity against G. mellonella, indicating their possible use for biocontrol.

Current State-of-the-Art MRI for Comprehensive Evaluation of Potential Living Liver Donors.

OBJECTIVE: This review focuses on the role of state-of-the-art MRI-based techniques for comprehensive evaluation of living donors providing single-visit assessment of the liver vasculature via MR angiography, of the biliary tract via conventional T2-weighted MR cholangiography and T1-weighted gadoxetate disodium-enhanced MR cholangiography, and of hepatic steatosis via T2*-corrected multiecho chemical shift-based water-fat separation MRI and high-speed T2-corrected multiecho MR spectroscopy. CONCLUSION: By using current state-of-the-art techniques, MRI can provide a one-stop-shop method for evaluation of the potential living liver donors.

SIMBA: a web tool for managing bacterial genome assembly generated by Ion PGM sequencing technology.

BACKGROUND: The evolution of Next-Generation Sequencing (NGS) has considerably reduced the cost per sequenced-base, allowing a significant rise of sequencing projects, mainly in prokaryotes. However, the range of available NGS platforms requires different strategies and software to correctly assemble genomes. Different strategies are necessary to properly complete an assembly project, in addition to the installation or modification of various software. This requires users to have significant expertise in these software and command line scripting experience on Unix platforms, besides possessing the basic expertise on methodologies and techniques for genome assembly. These difficulties often delay the complete genome assembly projects. RESULTS: In order to overcome this, we developed SIMBA (SImple Manager for Bacterial Assemblies), a freely available web tool that integrates several component tools for assembling and finishing bacterial genomes. SIMBA provides a friendly and intuitive user interface so bioinformaticians, even with low computational expertise, can work under a centralized administrative control system of assemblies managed by the assembly center head. SIMBA guides the users to execute assembly process through simple and interactive pages. SIMBA workflow was divided in three modules: (i) projects: allows a general vision of genome sequencing projects, in addition to data quality analysis and data format conversions; (ii) assemblies: allows de novo assemblies with the software Mira, Minia, Newbler and SPAdes, also assembly quality validations using QUAST software; and (iii) curation: presents methods to finishing assemblies through tools for scaffolding contigs and close gaps. We also presented a case study that validated the efficacy of SIMBA to manage bacterial assemblies projects sequenced using Ion Torrent PGM. CONCLUSION: Besides to be a web tool for genome assembly, SIMBA is a complete genome assemblies project management system, which can be useful for managing of several projects in laboratories. SIMBA source code is available to download and install in local webservers at http://ufmg-simba.sourceforge.net .

Production and chemical characterization of pigments in filamentous fungi.

Production of pigments by filamentous fungi is gaining interest owing to their use as food colourants, in cosmetics and textiles, and because of the important biological activities of these compounds. In this context, the objectives of this study were to select pigment-producing fungi, identify these fungi based on internal transcribed spacer sequences, evaluate the growth and pigment production of the selected strains on four different media, and characterize the major coloured metabolites in their extracts. Of the selected fungal strains, eight were identified as Aspergillus sydowii (CML2967), Aspergillus aureolatus (CML2964), Aspergillus keveii (CML2968), Penicillium flavigenum (CML2965), Penicillium chermesinum (CML2966), Epicoccum nigrum (CML2971), Lecanicillium aphanocladii (CML2970) and Fusarium sp. (CML2969). Fungal pigment production was influenced by medium composition. Complex media, such as potato dextrose and malt extract, favoured increased pigment production. The coloured compounds oosporein, orevactaene and dihydrotrichodimerol were identified in extracts of L. aphanocladii (CML2970), E. nigrum (CML2971), and P. flavigenum (CML2965), respectively. These results indicate that the selected fungal strains can serve as novel sources of pigments that have important industrial applications.

Secretome Analysis of Metarhizium anisopliae Under Submerged Conditions Using Bombyx mori Chrysalis to Induce Expression of Virulence-Related Proteins.

The entomopathogenic fungus Metarhizium anisopliae is used to control insect pests. This species is specialized for the secretion of an enzymatic complex consisting of proteases, lipases, and chitinases related to pathogenicity and virulence. In this context, the secretomes of strains IBCB 167 and IBCB 384 of M. anisopliae var. anisopliae, grown under submerged fermentation in the presence of chrysalis as an inducer, were analyzed. Analysis of two-dimensional gels showed qualitative and quantitative differences between secreted proteins in both isolates. Around 102 protein spots were analyzed, and 76 % of the corresponding proteins identified by mass spectrometry were grouped into different classes (hydrolases, oxidases, reductases, isomerases, kinases, WSC domains, and hypothetical proteins). Thirty-three per cent of all the proteins analyzed were found to be common in both strains. Several virulence-related proteins were identified as proteases and mannosidases. Endo-N-acetyl-ß-D-glucosaminidase expression was observed to be 10.14-fold higher for strain IBCB 384 than for strain IBCB 167, which may be an important contributor to the high virulence of IBCB 384 in Diatraea ssaccharalis. These results are important for elucidation of the host-pathogen relationship and the differences in virulence observed between the two strains.

Retinoblastoma in a pediatric oncology reference center in Southern Brazil.

BACKGROUND: Retinoblastoma (Rb) is the most common intraocular tumor diagnosed in children in Brazil. However, detailed information is lacking regarding patient clinical demographics. This study aimed to determine the clinical profile of patients with Rb who were treated in a public university hospital in southern Brazil from 1983 to 2012. METHODS: Patients' medical records were reviewed to retrospectively identify patients with a principal diagnosis of Rb. Rb was classified as hereditary or non-hereditary. Clinical staging was reviewed by an ophthalmologist. Statistical analysis was performed using SPSS. RESULTS: Of 165 patients with a diagnosis of Rb during this period, 140 were included in the study. Disease was unilateral in 65.0 % of patients, bilateral in 32.9 %, and trilateral in 2.1 %. The mean age at onset of the first sign/symptom was 18.1 month, and 35.7 % of patients were diagnosed during the first year of life. The most common presenting signs were leukocoria (73.6 %) and strabismus (20.7 %). The mean age at diagnosis was 23.5 months, and time to diagnosis was 5.4 months. In patients with clinical features of hereditary Rb, both onset of the first sign/symptom and diagnosis were at an earlier age than in patients without these features (12.3 vs 21.6 months [P = 0.001] and 15.9 vs 28.0 months [P < 0.001], respectively). However, there was no significant difference in overall survival between the two groups. Ocular stage at diagnosis was advanced in 76.5 % (Reese V) and 78.1 % (International Classification D or E). Of patients with unilateral and bilateral disease, 35.2 % and 34.8 %, respectively, had extraocular disease at diagnosis; 10.7 % had metastatic disease at diagnosis. Enucleation was observed in 88.1 % and exenteration in 11.9 % of patients; 93.6 % patients were followed until 2012, and 22.9 % relapsed. Overall survival was 86.4 %. CONCLUSIONS: Most Rb diagnoses are still diagnosed in advanced stages of the disease, considerably reducing overall survival time and the rate of eye and vision preservation.

Treatment of Disseminated Leishmaniasis With Liposomal Amphotericin B.

BACKGROUND: Disseminated leishmaniasis (DL) is a severe and emerging form of American tegumentary leishmaniasis, associated primarily with infection by Leishmania brasiliensis. DL is defined by the presence of ≥10 mixed-type lesions such as inflammatory papules and ulcers, located in ≥2 body parts. Most patients have hundreds of lesions all over the body, and mucosal involvement is detected in up to 44% of cases. DL is a difficult to cure disease and pentavalent antimony (Sb(v)) is used as standard treatment, its highest dosage being 20 mg/kg/day, for 30 days. However, less than 25% of DL cases will be cured after standard therapy, and the majority of cases will require more than one course of Sb(v) for a cure. In this context, new therapies are needed that offer a higher cure rate and a better safety profile, with convenience in drug administration. METHODS: We have evaluated liposomal amphotericin B in 20 patients with DL in an open clinical trial. The total dose ranged from 17 to 37 mg/kg, used in 7 to 14 days of treatment. RESULTS: Cure rate at 3 months after therapy was 70%. One relapse was documented 4 months after treatment, producing a final cure rate of 65%. Although liposomal amphotericin B was considered well tolerated, mild adverse events were documented in 75% of the patients. CONCLUSIONS: Liposomal amphotericin B is an effective therapy for DL, with a higher final cure rate of 75% observed when used in a total dose above 30 mg/kg. CLINICAL TRIALS REGISTRATION: NCT02025491.

Genome informatics and vaccine targets in Corynebacterium urealyticum using two whole genomes, comparative genomics, and reverse vaccinology.

BACKGROUND: Corynebacterium urealyticum is an opportunistic pathogen that normally lives on skin and mucous membranes in humans. This high Gram-positive bacteria can cause acute or encrusted cystitis, encrusted pyelitis, and pyelonephritis in immunocompromised patients. The bacteria is multi-drug resistant, and knowledge about the genes that contribute to its virulence is very limited. Two complete genome sequences were used in this comparative genomic study: C. urealyticum DSM 7109 and C. urealyticum DSM 7111. RESULTS: We used comparative genomics strategies to compare the two strains, DSM 7109 and DSM 7111, and to analyze their metabolic pathways, genome plasticity, and to predict putative antigenic targets. The genomes of these two strains together encode 2,115 non-redundant coding sequences, 1,823 of which are common to both genomes. We identified 188 strain-specific genes in DSM 7109 and 104 strain-specific genes in DSM 7111. The high number of strain-specific genes may be a result of horizontal gene transfer triggered by the large number of transposons in the genomes of these two strains. Screening for virulence factors revealed the presence of the spaDEF operon that encodes pili forming proteins. Therefore, spaDEF may play a pivotal role in facilitating the adhesion of the pathogen to the host tissue. Application of the reverse vaccinology method revealed 19 putative antigenic proteins that may be used in future studies as candidate drug or vaccine targets. CONCLUSIONS: The genome features and the presence of virulence factors in genomic islands in the two strains of C. urealyticum provide insights in the lifestyle of this opportunistic pathogen and may be useful in developing future therapeutic strategies.

Ionizing radiation exposure is still increasing in Crohn's disease: Who should be blamed?

BACKGROUND AND AIM: Crohn's disease (CD) patients undergo many radiological studies employing ionizing radiation for diagnosis and management purposes. Our aim was to assess the total radiation exposure of our patients over the years, to estimate the risk factors for exposure to high doses, and to correlate radiation exposure to immunosuppression. METHODS: The cumulative effective dose of radiation (CEDR) was calculated multiplying the number of imaging studies by the effective dose of each examination. RESULTS: A total of 451 patients with CD (226 female) were followed during 11.0 years (interquartile range [IQR]: 6.0-16.0), with 52.1% of the patients being classified with penetrating (B3) and 38.6% being steroid-dependent. About 16% were exposed to high-radiation dose levels (CEDR >50 mSv) and 4% were exposed to CEDR >100 mSv. The mean CEDR between age 26 and 35 years was 12.539 mSv and a significant dose of radiation (over 50 mSv) was achieved at a median age of 40 (IQR: 29.0-47.0). Abdominal-pelvic computed tomography scan was the examination that contributed the most for CEDR. Patients with B3 phenotype, previous surgery, azathioprine, and anti-tumor necrosis factor (TNF)-α therapy were exposed earlier on the course of the disease to CEDR >50 mSv (p < 0.001). The value of CEDR in the patients under immunosuppression mainly increased in the first year of immunosuppression. CONCLUSION: Penetrating phenotype, abdominal surgery, steroid resistance or steroid dependence, and treatment with anti-TNF-α and azathioprine were predictive factors for high CEDR. It was also demonstrated that immunosuppression and anti-TNF-α treatment were followed by a sustained increment of radiation exposure and that a significant dose of radiation was achieved <40 years of age.