Intermediate-risk pulmonary embolism: echocardiography predictors of clinical deterioration.

BACKGROUND: We determine the predictive value of transthoracic echocardiographic (TTE) metrics for clinical deterioration within 5 days in adults with intermediate-risk pulmonary embolism (PE). METHODS: This was a prospective observational study of intermediate-risk PE patients. To determine associations of TTE and clinical predictors with clinical deterioration, we used univariable analysis, Youden's index for optimal thresholds, and multivariable analyses to report odds ratios (ORs) or area under the curve (AUC). RESULTS: Of 306 intermediate-risk PE patients, 115 (37.6%) experienced clinical deterioration. PE patients who had clinical deterioration within 5 days had greater baseline right ventricle (RV) dilatation and worse systolic function than the group without clinical deterioration as indicated by the following: RV basal diameter 4.46 ± 0.77 versus 4.20 ± 0.77 cm; RV/LV basal width ratio 1.14 ± 0.29 versus 1.02 ± 0.24; tricuspid annular plane systolic excursion (TAPSE) 1.56 ± 0.55 versus 1.80 ± 0.52 cm; and RV systolic excursion velocity 10.40 ± 3.58 versus 12.1 ± 12.5 cm/s, respectively. Optimal thresholds for predicting clinical deterioration were: RV basal width 3.9 cm (OR 2.85 [1.64, 4.97]), RV-to-left ventricle (RV/LV) ratio 1.08 (OR 3.32 [2.07, 5.33]), TAPSE 1.98 cm (OR 3.3 [2.06, 5.3]), systolic excursion velocity 10.10 cm/s (OR 2.85 [1.75, 4.63]), and natriuretic peptide 190 pg/mL (OR 2.89 [1.81, 4.62]). Significant independent predictors were: transient hypotension 6.1 (2.2, 18.9), highest heart rate 1.02 (1.00, 1.03), highest respiratory rate 1.02 (1.00, 1.04), and RV/LV ratio 1.29 (1.14, 1.47). By logistic regression and random forest analyses, AUCs were 0.80 (0.73, 0.87) and 0.78 (0.70, 0.85), respectively. CONCLUSIONS: Basal RV, RV/LV ratio, and RV systolic function measurements were significantly different between intermediate-risk PE patients grouped by subsequent clinical deterioration.

Comprehensive curation and analysis of fungal biosynthetic gene clusters of published natural products.

Microorganisms produce a wide range of natural products (NPs) with clinically and agriculturally relevant biological activities. In bacteria and fungi, genes encoding successive steps in a biosynthetic pathway tend to be clustered on the chromosome as biosynthetic gene clusters (BGCs). Historically, "activity-guided" approaches to NP discovery have focused on bioactivity screening of NPs produced by culturable microbes. In contrast, recent "genome mining" approaches first identify candidate BGCs, express these biosynthetic genes using synthetic biology methods, and finally test for the production of NPs. Fungal genome mining efforts and the exploration of novel sequence and NP space are limited, however, by the lack of a comprehensive catalog of BGCs encoding experimentally-validated products. In this study, we generated a comprehensive reference set of fungal NPs whose biosynthetic gene clusters are described in the published literature. To generate this dataset, we first identified NCBI records that included both a peer-reviewed article and an associated nucleotide record. We filtered these records by text and homology criteria to identify putative NP-related articles and BGCs. Next, we manually curated the resulting articles, chemical structures, and protein sequences. The resulting catalog contains 197 unique NP compounds covering several major classes of fungal NPs, including polyketides, non-ribosomal peptides, terpenoids, and alkaloids. The distribution of articles published per compound shows a bias toward the study of certain popular compounds, such as the aflatoxins. Phylogenetic analysis of biosynthetic genes suggests that much chemical and enzymatic diversity remains to be discovered in fungi. Our catalog was incorporated into the recently launched Minimum Information about Biosynthetic Gene cluster (MIBiG) repository to create the largest known set of fungal BGCs and associated NPs, a resource that we anticipate will guide future genome mining and synthetic biology efforts toward discovering novel fungal enzymes and metabolites.

Delay in Time to Antibiotics for De Novo Inpatient Neutropenic Fever May Not Impact Overall Survival for Patients With a Cancer Diagnosis.

Neutropenic fever (NF) is an oncologic emergency for which expert consensus recommends that anti-pseudomonas antibiotics be administered within 60 minutes of detection. This study investigated whether delays in time to antibiotics (TTA) impacted overall survival (OS) for patients with hematological malignancies who developed inpatient NF via a retrospective cohort study of 187 de novo NF cases categorized by TTA (<1, 1-2, 2-3, 3-4 and >4 hours). OS at 180 days post-NF episode was compared using Kaplan-Meier estimates and multivariable Cox proportional hazards model. TTA did not significantly affect OS (P = 0.420). Patients with Charleston Comorbidity Indexes ≥3, a measure of overall health, had higher hazard (hazard ratio [HR] = 2.728, 95% confidence interval, 1.265-5.882, P = 0.010). TTA delays in the hospital may not be long enough to cause significant patient harm. Larger studies may be needed to detect small, but significant mortality differences.

Gender disparities among leadership in academic surgical publishing over the past decade.

BACKGROUND: Women account for 19 % of practicing surgeons in the United States, with representation decreasing with higher academic rank. Less is known about the proportion of women in editorial leadership positions at surgical journals. The objective of this study was to examine gender representation among editorial leadership at high-impact surgical journals. METHODS: The five journals with the highest impact factors in general, cardiothoracic, plastics, otolaryngology, orthopedics, urology, vascular, and neurosurgery were identified. Data were abstracted on the proportion of women editors-in-chief (EIC) and editorial board members between 2010 and 2020 to determine how these demographics changed over time. RESULTS: Multiple fields had no women EIC over the past decade (orthopedics, urology, cardiothoracic, neurosurgery). In all other fields, women were a minority of EIC. In 2020, women made up 7.9 % of EIC and 11.1 % of editorial boards in surgical journals. CONCLUSIONS: Women remain under-represented among leadership at high-impact surgical journals, with varying improvement over the past decade among different subspecialties.

Commensal Microbes Induce Serum IgA Responses that Protect against Polymicrobial Sepsis.

Serum immunoglobulin A (IgA) antibodies are readily detected in mice and people, but the mechanisms underlying the induction of serum IgA and its role in host protection remain uncertain. We report that select commensal bacteria induce several facets of systemic IgA-mediated immunity. Exposing conventional mice to a unique but natural microflora that included several members of the Proteobacteria phylum led to T cell-dependent increases in serum IgA levels and the induction of large numbers of IgA-secreting plasma cells in the bone marrow. The resulting serum IgA bound to a restricted collection of bacterial taxa, and antigen-specific serum IgA antibodies were readily induced after intestinal colonization with the commensal bacterium Helicobacter muridarum. Finally, movement to a Proteobacteria-rich microbiota led to serum IgA-mediated resistance to polymicrobial sepsis. We conclude that commensal microbes overtly influence the serum IgA repertoire, resulting in constitutive protection against bacterial sepsis.