A clinical predictive model of candidaemia by Candida auris in previously colonized critically ill patients.

OBJECTIVES: Candida auris is an emerging multidrug-resistant fungus that has been associated with nosocomial outbreaks with high rates of mortality and transmission. The aim of this study was to perform a retrospective cohort analysis of risk factors and to build a scoring method for estimating the risk of candidaemia in colonized critically ill patients. METHODS: We performed a retrospective observational cohort study of patients aged ≥15 years colonized by C. auris in the 3-year period between March 2016 and March 2019. Epidemiological, clinical, laboratory and microbiological data were collected. We developed a predictive model for candidaemia using elastic net multivariable logistic regression techniques, assessed its discriminative capacity, and internally validated it using bootstrap resampling. RESULTS: Two-hundred and six patients were enrolled in the cohort for derivation and internal validation. Thirty-seven out of 206 patients developed candidaemia. Total parenteral nutrition was the foremost risk factor (adjusted OR 3.73); previous surgery (adjusted OR 1.03), sepsis (adjusted OR 1.75), previous exposure to antifungal agents (adjusted OR 1.17), arterial catheters (adjusted OR 1.46), central venous catheters (adjusted OR 1.21), presence of advanced chronic kidney disease (adjusted OR 1.35) and multifocal colonization (adjusted OR of unifocal colonization 0.46) were proven to be independent predictors of candidaemia in our cohort. The corresponding area under the curve (AUC) of the elastic net regularized predictive model was 0.89 (95%CI 0.826; 0.951). After performing the internal validation by generating 500 bootstrap replications, the model still showed great accuracy, with a resulting AUC of 0.84. CONCLUSION: Our study provides evidence on the independent predisposing factors for candidaemia. It may help predict its estimated risk and may identify a high-risk population that could benefit from early or prophylactic antifungal treatment after external validation in other cohorts.

[Repetitive resection and intrasurgery radiation therapy of brain malignant gliomas: history of question and modern state of problem]. / Povtornaia rezektsiia i intraoperatsionnaia luchevaia terapiia zlokachestvennykh gliom golovnogo mozga: istoricheskii ékskurs i sovremennoe sostoianie problemy.

Numerous studies have shown that the degree of primary resection of malignant gliomas of the brain (MG) directly correlates with rates of relapse-free and overall patient survival. Currently, there is no unequivocal opinion regarding the indications and effectiveness of repeated resection in relapse of MG after combined treatment. Surgical intervention, taking into account the pathomorphological features of these tumors, is not healing and should be supplemented with certain methods of adjuvant treatment. The article reviews and analyzes publications devoted to repeated resection and various methods of intraoperative radiation therapy in the treatment of MG. Based on the analysis, the authors of the article came to the conclusion that it is advisable to start their own research on the use of intraoperative balloon brachytherapy in the treatment of recurrent MG based on modern technological solutions.

Maternal n-6 and n-3 fatty acid status during pregnancy is related to infant heart rate and heart rate variability: An exploratory study.

Early life heart rate (HR) and heart rate variability (HRV) reflect autonomic system maturation. Intervention with n-3 long chain polyunsaturated fatty acids (LCPUFAs) during pregnancy favorably affects fetal HR and HRV, complementing previous observations for n-3 LCPUFA intervention during infancy. The relationship between maternal fatty acid status during pregnancy and infant HR/HRV has not previously been assessed. The aim of this study was to explore associations between maternal n-6 and n-3 fatty acid status during pregnancy and infant HR and HRV at 2 weeks, 4 months, and 6 months of age using linear regression models. Maternal n-3 fatty acids were inversely related to infant HR and positively related to HRV. Conversely, maternal n-6 fatty acids were positively related to infant HR and inversely related to HRV. These data build on existing literature evidencing a role for n-3 fatty acids in accelerating autonomic development and link n-6 fatty acids to HR/HRV.

Update on the diagnosis of invasive fungal infection.

The number of patients at risk of suffering invasive fungal infection (IFI) is increasing. Because of its high mortality, new rapid and accurate diagnostic tools are needed. Last advances in invasive candidiasis diagnosis comprise Peptide Nucleic Acid Fluorescent In-Situ Hybridization (PNA-FISH), direct MALDI-TOF or multiplex acid nucleic testing. While all of them rely in positive blood cultures, T2Candida uses PCR coupled with T2Magnetic resonance detection directly in whole blood, allowing detection of 1-3 UFC/mL of Candida in about four hours. Beyond galactomannan (GM), novelties in IFI caused by molds include the international standardization of PCR techniques, with several commercial kits available. A combination of GM and PCR appears to be a good diagnostic strategy for invasive aspergillosis. PCR coupled to electrospray ionization/mass spectrometry and detection of volatile organic compounds in exhaled air by gas chromatography/mass spectrometry are other promising approaches to IFI diagnostic that still need to be validated.

Pregnant Women in Louisiana Are Not Meeting Dietary Seafood Recommendations.

Background. The 2015-2020 Dietary Guidelines for Americans recommend that pregnant women and women of childbearing ages consume 8-12 oz. of seafood per week. Fish are the major dietary source of omega-3 long chain polyunsaturated fatty acids, which have benefits for the mother and fetus. Methods. In this observational study, we investigated dietary habits of pregnant women in Baton Rouge, Louisiana, USA, to determine if they achieve recommended seafood intake. A print survey, which included commonly consumed foods from protein sources (beef, chicken, pork, and fish), was completed by pregnant women at a single-day hospital convention for expecting families in October 2015. Women (n = 221) chose from six predefined responses to answer how frequently they were consuming each food. Results. Chicken was consumed most frequently (75% of women), followed by beef (71%), pork (65%), and fish (22%), respectively. Consumption frequency for the most consumed fish (catfish, once per month) was similar to or lower than that of the least consumed beef, chicken, and pork foods. Consumption frequency for the most consumed chicken and beef foods was at least once per week. Conclusion. Our data indicate that pregnant women in Louisiana often consume protein sources other than fish and likely fail to meet dietary seafood recommendations.

Intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) in a patient with left breast cancer and pectus excavatum

INTRODUCTION: Pectus excavatum is a frequent anomaly. It represents a challenge for adjuvant radiotherapy in the conservative treatment of breast cancer. Primary objective of this study is to compare dosimetric outcomes, normal tissue complication probability (NTCP), and integral dose using four radiation techniques. Secondary objective is to describe acute toxicity and setup errors. METHODS AND MATERIALS: A 57-year-old female patient with an inner quadrant, left breast, ductal carcinoma in situ, was identified. Whole breast was prescribed with 50 Gy in 25 fractions. Boost planning target volume (PTV) was prescribed with 60 Gy in 30 fractions for sequential boost (SB) plans or 57.5 Gy in 25 fractions in the simultaneous integrated boost (SIB) plan. All plans were normalized to deliver 47.5 Gy to 95 % of the breast PTV. Daily image-guided radiotherapy (IGRT) was performed. Setup deviations were described. RESULTS: Constraints were not accomplished for heart when using intensity modulated radiotherapy (IMRT) + SB or conformal radiotherapy with three photon fields and SB. Left lung constraint was not achieved by any of the techniques in comparison. IMRT + SIB and conformal photons and electrons + SB plan were closer to the objective. Integral doses were lower with IMRT for heart and ipsilateral lung; however, it were higher for contralateral breast and lung. Coverage and tumoral conformity indexes were similar for all techniques in comparison. Greater inhomogeneity was observed with the photons and electrons + SB. IMRT + SIB treatment was administered daily with grade I skin toxicity. The highest setup error was observed in Y direction. CONCLUSION: Planning target volume coverage was similar with the four techniques. Homogeneity was superior with both IMRT plans. A good balance between dose constraints for organs at risk, PTV coverage, homogeneity, and NTCP was observed with IMRT + SIB. The documented daily setup error justifies the use of online IGRT (AU)

[Oncolytic viruses in the therapy of gliomas].

Despite the advances of modern medicine, malignant glioblastoma cure remains an elusive goal. Both the invasive nature and location in vital areas of the brain make this type of tumors difficult for surgical treatment, while the current adjuvant therapy is not as successful as expected. Frequent recurrence and invasiveness of malignant gliomas is due to resistance of glioma stem cells to conventional radiation and chemotherapy. Technological advances in constructing recombinant viruses have allowed creating strains with high oncolytic activity toward glial tumors. Many of these strains have passed Phase I of clinical trials and demonstrated high safety. Despite the obvious potential of the approach, efficiency of the existing strains is still far from being sufficient for effectively curing the disease and require further improvement. The review summarizes results obtained with the most successful variants of oncolytic viruses that come down to the clinical trials and discusses the prospects for new approaches in virotherapy of malignant gliomas.

Reduction of simian-human immunodeficiency virus 89.6P viremia in rhesus monkeys by recombinant modified vaccinia virus Ankara vaccination.

Since cytotoxic T lymphocytes (CTLs) are critical for controlling human immunodeficiency virus type 1 (HIV-1) replication in infected individuals, candidate HIV-1 vaccines should elicit virus-specific CTL responses. In this report, we study the immune responses elicited in rhesus monkeys by a recombinant poxvirus vaccine and the degree of protection afforded against a pathogenic simian-human immunodeficiency virus SHIV-89.6P challenge. Immunization with recombinant modified vaccinia virus Ankara (MVA) vectors expressing SIVmac239 gag-pol and HIV-1 89.6 env elicited potent Gag-specific CTL responses but no detectable SHIV-specific neutralizing antibody (NAb) responses. Following intravenous SHIV-89.6P challenge, sham-vaccinated monkeys developed low-frequency CTL responses, low-titer NAb responses, rapid loss of CD4+ T lymphocytes, high-setpoint viral RNA levels, and significant clinical disease progression and death in half of the animals by day 168 postchallenge. In contrast, the recombinant MVA-vaccinated monkeys demonstrated high-frequency secondary CTL responses, high-titer secondary SHIV-89.6-specific NAb responses, rapid emergence of SHIV-89.6P-specific NAb responses, partial preservation of CD4+ T lymphocytes, reduced setpoint viral RNA levels, and no evidence of clinical disease or mortality by day 168 postchallenge. There was a statistically significant correlation between levels of vaccine-elicited CTL responses prior to challenge and the control of viremia following challenge. These results demonstrate that immune responses elicited by live recombinant vectors, although unable to provide sterilizing immunity, can control viremia and prevent disease progression following a highly pathogenic AIDS virus challenge.

Immunization with recombinant canarypox vectors expressing membrane-anchored glycoprotein 120 followed by glycoprotein 160 boosting fails to generate antibodies that neutralize R5 primary isolates of human immunodeficiency virus type 1.

Antibodies generated by candidate HIV-1 vaccines in a phase I clinical trial were assessed for neutralizing activity with a panel of eight well-characterized, genetically diverse clade B primary isolates having an R5 phenotype. The vaccines consisted of one of three different recombinant canarypox vectors expressing membrane-anchored HIV-1(MN)gp120 (ALVAC vCP205, vCP1433, and vCP1452) followed by boosting with a soluble gp160 hybrid consisting of MNgp120 and the majority of gp41 from strain IIIB. Serum samples from a subset of volunteers in each arm of the trial, containing moderate to high titers of neutralizing antibodies to HIV-1 MN, were analyzed. Competition assays with peptides revealed that the majority of neutralizing activity was specific for the MN-V3 loop. Despite MN-specific neutralization titers that sometimes exceeded 1:500, no neutralization of primary isolates was detected and, in some cases, mild infection enhancement was observed. In addition, little or no neutralization of the HIV-1 IIIB heterologous T cell line-adapted strain of virus was detected. These results reinforce the notion that monovalent HIV-1 ENV is a poor immunogen for generating cross-reactive neutralizing antibodies.

Correlation of DNA fragmentation and chromatin condensation in apoptotic nuclei of the Ser 6 mouse retina.

The form of cell death known as apoptosis was first described in thymocytes. The hallmarks of apoptosis include chromatin condensation, membrane blebbing, formation of apoptotic bodies, and DNA fragmentation. DNA fragmentation can be visualized morphologically by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method that labels the cut DNA ends. However, at the light microscopic (LM) level, TUNEL-positive nuclei cannot readily be correlated with the other hallmarks of apoptosis. In the retina, chromatin condensation and DNA fragmentation are the major features of developmental cell death as well as photoreceptor degeneration. We performed TUNEL at the electron microscopic (EM) level, which permitted correlation of DNA fragmentation with chromatin condensation. We studied the retinas of transgenic mice (Ser 6) expressing the Pro347Ser mutant rhodopsin gene during developmental cell death (age 7 days) and photoreceptor degeneration (age 21 days). We found that 90% of the nuclei showing chromatin condensation were TUNEL positive as well. Our results demonstrated DNA fragmentation and chromatin condensation in the same cells as they underwent apoptosis in vivo, confirming the notion that these processes are concomitant events, and by implication, that activation of an endogenous endonuclease is an important step in the death process of retinal neurons.

Cellular interactions implicated in the mechanism of photoreceptor degeneration in transgenic mice expressing a mutant rhodopsin gene.

Photoreceptors of transgenic mice expressing a mutant rhodopsin gene (Pro347-->Ser) slowly degenerate. The mechanism of degeneration was studied by aggregation of embryos of normal and transgenic mice to form chimeras. In these chimeras, mosaicism was observed in the coat color, retinal pigment epithelium, and retina. In the retina, the genotype of adjacent patches of normal and transgenic photoreceptors was determined by in situ hybridization with a transgene-specific RNA probe. Photoreceptors in the chimeric retina degenerated uniformly, independent of the genotype and similar to the photoreceptors in transgenic mice. However, the chimeric retinas showed varying proportions of normal and transgenic cells. The chimeric retina with a nearly even proportion of normal and transgenic photoreceptors displayed uniform but slower degeneration than that observed in a transgenic mouse of the same age. Our results demonstrate non-autonomy of gene action for the mutated rhodopsin gene and imply that cellular interactions between photoreceptors in the retina probably play a role in degeneration.

Ultrastructural study of Norrie's disease.

We studied the clinicopathologic and ultrastructural features of a full-term infant with Norrie's disease. The infant had bilateral retrolental fibrous vascular masses and retinal detachment with no other apparent physical abnormalities and no family history of ocular defects. A vitrectomy and a membrane peeling were attempted, and specimens of the retina, the retrolental membrane, and a vascularized epiretinal peripheral mass were examined by light and electron microscopy. The retrolental membrane was composed of layered collagenous tissue and contained structures resembling blood vessels. Inner and outer neuroblastic layers were identified in the retinal tissue, but no vessels were present. In the epiretinal mass, portions of retina and cortical vitreous were seen along with primitive vascular structures. The histologic appearance of these specimens suggests that the major pathologic event of Norrie's disease occurs in the retina in the third to fourth gestational month. We believe the subsequent ocular abnormalities found in this patient were secondary to this early retinal malformation and did not represent a progressive ocular disorder.

Detección del cáncer de esófago y enfermedades premalignas mediante citología exfoliativa con balón

Se estudia un grupo de pacientes por medio de citología del esófago tomada con un balón inflable diseñado y construído por el autor, con el fín de conocer su eficacia para diagnosticar la displasia y el cáncer esofágico. Hubo dos grupos de pacientes: sintomáticos (grupo 1), remitidos para estudio de endoscopia y voluntarios asintomáticos ( Grupo 11). La edad promedio de los dos fue de 47 años con límites de 18 y 22 años; hubo 469 mujeres y 217 hombres. En el primer grupo se detectaron por la citología 6 de 7 tumores y 21 casos de displasia únicamente. En total hubo 686 pacientes de los cuales el 4.2 por ciento tenían displasia y el 1 por ciento cáncer. Mediante la citología y la patología, simultáneas, se estudiaron 109 casos y en la displasia la correlación fue el 92.3 por ciento y en el cáncer del 85.7 por ciento. Sólo hubo un falso negativo y no se presentaron falsos positivos. Se revisa la literatura y nuestros hallazgos son compatibles con aquellos descritos en zonas de alto riesgo. Esto nos permite recomendar el método para el estudio rutinario o de tamizado, de las enfermedades malignas y premalignas del esófago con la ventaja de ser esta una técnica fácil, bien tolerada, que proporciona un alto índice de seguridad frente a la endoscopia y la radiología y en consecuencia, por ser más económica, se ajusta a nuestras necesidades