Dosing of caspofungin based on a pharmacokinetic/pharmacodynamic index for the treatment of invasive fungal infections in critically ill patients on continuous venovenous haemodiafiltration

Introduction

The study objective was to evaluate the efficacy of different dosages of caspofungin in the treatment of invasive candidiasis and aspergillosis, in relation to the probability of pharmacokinetic/pharmacodynamic (PK/PD) target attainment, using modelling and Monte Carlo simulations in critically ill adult patients on continuous haemodiafiltration.

“Does this Look Infected to You?” Social Network Predictors of Dental Help-Seeking Among Mexican Immigrants

Compared to U.S. born Latinos, Mexican immigrants (MAs) have diminished health care access and face substantial barriers to accessing needed dental health services. However, little research has examined how MAs social networks shape their use of dental health services. Using data from 332 Mexican immigrants to the Midwest, this research examines the significance of individual and egocentric network characteristics on two measures of dental health service utilization. Findings reveal that network size, network dental service utilization, and the frequency with which MAs discuss acute problems with network ties, positively correspond to use of oral health services. Conversely, embeddedness in networks where ties hassle egos about dental issues and have low levels of dental health knowledge correspond to lower odds of using these services. This research is among the first to use ego network data and methods to examine the ways network characteristics shape oral health behaviors among this underserved population.     

Digital breast tomosynthesis and contrast‐enhanced dual‐energy digital mammography alone and in combination compared to 2D digital synthetized mammography and MR imaging in breast cancer detection and classification

To compare diagnostic performance of contrast‐enhanced dual‐energy digital mammography (CEDM) and digital breast tomosynthesis (DBT) alone and in combination compared to 2D digital mammography (MX) and dynamic contrast‐enhanced MRI (DCE‐MRI) in women with breast lesions. We enrolled 100 consecutive patients with breast lesions (BIRADS 3‐5 at imaging or clinically suspicious). CEDM, DBT, and DCE‐MRI 2D were acquired. Synthetized MX was obtained by DBT. A total of 134 lesions were investigated on 111 breasts of 100 enrolled patients: 53 were histopathologically proven as benign and 81 as malignant. Nonparametric statistics and receiver operating characteristic (ROC) curve were performed. Two‐dimensional synthetized MX showed an area under ROC curve (AUC) of 0.764 (sensitivity 65%, specificity 80%), while AUC was of 0.845 (sensitivity 80%, specificity 82%) for DBT, of 0.879 (sensitivity 82%, specificity 80%) for CEDM, and of 0.892 (sensitivity 91%, specificity 84%) for CE‐MRI. DCE‐MRI determined an AUC of 0.934 (sensitivity 96%, specificity 88%). Combined CEDM with DBT findings, we obtained an AUC of 0.890 (sensitivity 89%, specificity 74%). A difference statistically significant was observed only between DCE‐MRI and CEDM (P = .03). DBT, CEDM, CEDM combined to tomosynthesis, and DCE‐MRI had a high ability to identify multifocal and bilateral lesions with a detection rate of 77%, 85%, 91%, and 95% respectively, while 2D synthetized MX had a detection rate for multifocal lesions of 56%. DBT and CEDM have superior diagnostic accuracy of 2D synthetized MX to identify and classify breast lesions, and CEDM combined with DBT has better diagnostic performance compared with DBT alone. The best results in terms of diagnostic performance were obtained by DCE‐MRI. Dynamic information obtained by time‐intensity curve including entire phase of contrast agent uptake allows a better detection and classification of breast lesions.     

Best practices to optimize utilization of the National Living Donor Assistance Center for the financial assistance of living organ donors

Living organ donors face direct costs when donating an organ, including transportation, lodging, meals, and lost wages. For those most in need, the National Living Donor Assistance Center (NLDAC) provides reimbursement to defray travel and subsistence costs associated with living donor evaluation, surgery, and follow‐up. While this program currently supports 9% of all US living donors, there is tremendous variability in its utilization across US transplant centers, which may limit patient access to living donor transplantation. Based on feedback from the transplant community, NLDAC convened a Best Practices Workshop on August 2, 2018, in Arlington, VA, to identify strategies to optimize transplant program utilization of this valuable resource. Attendees included team members from transplant centers that are high NLDAC users; the NLDAC program team; and Advisory Group members. After a robust review of NLDAC data and engagement in group discussions, the workgroup identified concrete best practices for administrative and transplant center leadership involvement; for individuals filing NLDAC applications at transplant centers; and to improve patient education about potential financial barriers to living organ donation. Multiple opportunities were identified for intervention to increase transplant programs’ NLDAC utilization and reduce financial burdens inhibiting expansion of living donor transplantation in the United States.     

SARS-CoV-2 and Placenta: New Insights and Perspectives

The study of SARS-CoV-2 positive pregnant women is of some importance for gynecologists, obstetricians, neonatologists and women themselves. In recent months, new works have tried to clarify what happens at the fetal–placental level in women positive for the virus, and different pathogenesis mechanisms have been proposed. Here, we present the results of a large series of placentas of Coronavirus disease (COVID) positive women, in a reference center for COVID-positive pregnancies, on which we conducted histological, immunohistochemical and electron microscopy investigations. A case–control study was conducted in order to highlight any histopathological alterations attributable to SARS-CoV-2. The prevalence of maternal vascular malperfusion was not significantly different between cases and controls (54.3% vs. 43.7% p = 0.19), whereas the differences with regard to fetal vascular malperfusion (21.1% vs. 4.2% p < 0.001) were significant. More frequent in cases with respect to controls were decidual arteriopathy (40.9% vs. 1.4% p < 0.0001), decidual inflammation (32.4% vs. 0.7% p < 0.0001), perivillous fibrin deposition (36.6% vs. 3.5% p < 0.0001) and fetal vessel thrombi (22.5% vs. 0.7% p < 0.0001). No significant differences in the percentage of terminal villous hyperplasia and chorioamnionitis were observed between the two groups. As the pandemic continues, these studies will become more urgent in order to clarify the possible mechanism of maternal–fetal transmission of the virus.     

Is the First of the Two Born Saved? A Rare and Dramatic Case of Double Placental Damage from SARS-CoV-2

The current coronavirus pandemic has affected, in a short time, various and different areas of medicine. Among these, the obstetric field has certainly been touched in full, and the knowledge of the mechanisms potentially responsible for placental damage from SARS-CoV-2 occupy a certain importance. Here we present here a rare case of dichorionic twins born at 30 weeks and 4 days of amenorrhea, one of whom died in the first few hours of life after placental damages potentially related to SARS-CoV-2. We also propose a brief review of the current literature giving ample emphasis to similar cases described.     

Small genome of the fungus Escovopsis weberi,a specialized disease agent of ant agriculture

Many microorganisms with specialized lifestyles have reduced genomes. This is best understood in beneficial bacterial symbioses, where partner fidelity facilitates loss of genes necessary for living independently. Specialized microbial pathogens may also exhibit gene loss relative to generalists. Here, we demonstrate that Escovopsis weberi, a fungal parasite of the crops of fungus-growing ants, has a reduced genome in terms of both size and gene content relative to closely related but less specialized fungi. Although primary metabolism genes have been retained, the E. weberi genome is depleted in carbohydrate active enzymes, which is consistent with reliance on a host with these functions. E. weberi has also lost genes considered necessary for sexual reproduction. Contrasting these losses, the genome encodes unique secondary metabolite biosynthesis clusters, some of which include genes that exhibit up-regulated expression during host attack. Thus, the specialized nature of the interaction between Escovopsis and ant agriculture is reflected in the parasite’s genome.The highly evolved agricultural lifestyle of leaf-cutting ants has attracted particular attention because these ants cultivate a symbiotic fungus that serves as their major food source. These ants cut leaves, preprocess them into small pieces, and feed them to the cultivated fungus (1). The capacity of the cultivated fungus to break down plant material gives ant agriculturalists access to the vast nutrient stores locked within neotropical plants (Fig. 1A) (2–5). The symbiosis between fungus-growing ants and their cultivated fungi has persisted for at least 50 million years (6).Open in a separate windowFig. 1.Escovopsis weberi, a specialized mycoparasite of the fungus-growing ant symbiosis, has a small genome compared with other Pezizomycotina fungi. (A) Both fungus-growing ants and the mycoparasite E. weberi use the ants’ cultivated fungi as their primary food source. The ability of the cultivated fungi to efficiently break down plant material gives both consumers access to the biomass of neotropical plants. (B) Size and protein-coding gene content of genomes of diverse fungi in the Pezizomycotina. Bayesian phylogeny estimated using partial amino acid alignments of three genes (Rpb1, Rpb2, ef1-α). All posterior probabilities are greater than 0.95. Phylogeny is rooted with Sacchormyces cervesiae (not shown). (C) Relationship between genome size and gene content. A list of genomes included in this panel is in SI Appendix, Table S1.Like human agriculture, ant agriculture is hampered by disease. The ants’ fungal crops are attacked and consumed by fungal parasites of the genus Escovopsis (Ascomycota, Pezizomycotina: anamorphic Hypocreales) (Fig. 1A) (7), which have evolved in association with the ants and their cultivated fungi (8). Escovopsis infection can have detrimental impacts on garden health and, consequently, on the survival of ant colonies (9, 10). Such mycoparasitism, the phenomenon whereby one fungus is parasitic on another fungus, is rare. It is most well-known for species from the genus Trichoderma, some of which are used as biocontrol agents for fungal diseases and others of which attack human-cultivated fungi (11–13). In contrast to Trichoderma species, however, Escovopsis species grow poorly in their hosts’ absence (SI Appendix, Figs. S1 and S2).Escovopsis species have never been isolated outside of fungus-growing ant colonies, and different strains of Escovopsis are capable of attacking the fungi grown by different fungus-growing ant species (8, 14, 15). The long-term, specialized evolutionary history of the association between Escovopsis and their hosts provides a unique venue to explore the consequences of host specialization on pathogen genome evolution. Here, we assemble and annotate the genome of a strain of Escovopsis weberi. Consistent with expectations under an evolutionary transition toward using a narrow host range, and similar to many other specialized, host-associated microbes (16, 17), E. weberi exhibits gene loss. Contrasting other fungal pathogens, the large genomes of which are expanded with genetic elements that influence host adaptation (18), the genome size of Escovopsis is small compared with those of its closest sequenced relatives.