A case of rapid-onset daptomycin-induced neutropenia

A 75-year-old Caucasian woman was transferred to a tertiary academic medical center for management of a foul smelling, non-draining, unstageable sacral pressure ulcer. Upon admission, the patient's laboratory data was notable for a white blood cell count (WBC) of 14.90 x 10-3/[mu]L and absolute neutrophil count of 12.24 x 10-3 /[mu]L. After a complicated hospital course the patient was initiated on daptomycin 6 mg/kg (300 mg) daily in response to wound cultures detecting Enterococcus faecium susceptible only to daptomycin and linezolid. Starting 96 hours after daptomycin initiation, there was a profound reduction in the patient's WBC, reaching a nadir of 1.63 x 10-3 /[mu]L after 12 days of therapy. Prior to documented resolution of her blood dyscrasia the patient was transferred to hospice care and use of antimicrobial therapy was withdrawn. The Naranjo Adverse Drug Reaction Probability Score demonstrated a probable relationship (score equal to 6) between daptomycin and the development of neutropenia. Unlike previous reports of daptomycin-induced neutropenia and/or thrombocytopenia, where patients received prolonged courses of daptomycin with doses ranging from 6-10 mg/kg, this case describes a much more rapid onset of neutropenia that occurred at a dose of 6 mg/kg/day. This case reports highlights the risk for daptomycin to induce neutropenia in patients receiving traditional dosing, not just at higher doses, and within a shorter time-frame than previously documented. Healthcare providers should be cognizant of this adverse reaction, and diligent in monitoring for adverse events, associated with daptomycin use even when used for short courses or at traditional doses

Reduction of CO\u3csub\u3e2\u3c/sub\u3e By a Masked Two-Coordinate Cobalt(I) Complex and Characterization of a Proposed Oxodicobalt(II) Intermediate

Fixation and chemical reduction of CO2 are important for utilization of this abundant resource, and understanding the detailed mechanism of C-O cleavage is needed for rational development of CO2 reduction methods. Here, we describe a detailed analysis of the mechanism of the reaction of a masked two-coordinate cobalt(i) complex, LtBuCo (where LtBu = 2,2,6,6-tetramethyl-3,5-bis[(2,6-diisopropylphenyl)imino]hept-4-yl), with CO2, which yields two products of C-O cleavage, the cobalt(i) monocarbonyl complex LtBuCo(CO) and the dicobalt(ii) carbonate complex (LtBuCo)2(μ-CO3). Kinetic studies and computations show that the κN,η6-arene isomer of LtBuCo rearranges to the κ2N,N′ binding mode prior to binding of CO2, which contrasts with the mechanism of binding of other substrates to LtBuCo. Density functional theory (DFT) studies show that the only low-energy pathways for cleavage of CO2 proceed through bimetallic mechanisms, and DFT and highly correlated domain-based local pair natural orbital coupled cluster (DLPNO-CCSD(T)) calculations reveal the cooperative effects of the two metal centers during facile C-O bond rupture. A plausible intermediate in the reaction of CO2 with LtBuCo is the oxodicobalt(II) complex LtBuCoOCoLtBu, which has been independently synthesized through the reaction of LtBuCo with N2O. The rapid reaction of LtBuCoOCoLtBu with CO2 to form the carbonate product indicates that the oxo species is kinetically competent to be an intermediate during CO2 cleavage by LtBuCo. LtBuCoOCoLtBu is a novel example of a thoroughly characterized molecular cobalt-oxo complex where the cobalt ions are clearly in the +2 oxidation state. Its nucleophilic reactivity is a consequence of high charge localization on the μ-oxo ligand between two antiferromagnetically coupled high-spin cobalt(ii) centers, as characterized by DFT and multireference complete active space self-consistent field (CASSCF) calculations

The Brain Atlas Concordance Problem: Quantitative Comparison of Anatomical Parcellations

Many neuroscientific reports reference discrete macro-anatomical regions of the brain which were delineated according to a brain atlas or parcellation protocol. Currently, however, no widely accepted standards exist for partitioning the cortex and subcortical structures, or for assigning labels to the resulting regions, and many procedures are being actively used. Previous attempts to reconcile neuroanatomical nomenclatures have been largely qualitative, focusing on the development of thesauri or simple semantic mappings between terms. Here we take a fundamentally different approach, discounting the names of regions and instead comparing their definitions as spatial entities in an effort to provide more precise quantitative mappings between anatomical entities as defined by different atlases. We develop an analytical framework for studying this brain atlas concordance problem, and apply these methods in a comparison of eight diverse labeling methods used by the neuroimaging community. These analyses result in conditional probabilities that enable mapping between regions across atlases, which also form the input to graph-based methods for extracting higher-order relationships between sets of regions and to procedures for assessing the global similarity between different parcellations of the same brain. At a global scale, the overall results demonstrate a considerable lack of concordance between available parcellation schemes, falling within chance levels for some atlas pairs. At a finer level, this study reveals spatial relationships between sets of defined regions that are not obviously apparent; these are of high potential interest to researchers faced with the challenge of comparing results that were based on these different anatomical models, particularly when coordinate-based data are not available. The complexity of the spatial overlap patterns revealed points to problems for attempts to reconcile anatomical parcellations and nomenclatures using strictly qualitative and/or categorical methods. Detailed results from this study are made available via an interactive web site at http://obart.info

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Replacing Fertilizer with Dried Distillers’ Grains in Stocker Cattle Systems on Southern Great Plains Old World Bluestem, USA

The objective was to examine the effects of dried distillers’ grains supplementation and fertilization strategies on the cattle performance and resource use efficiency of stocker cattle grazing on Plains Old World bluestem. Over 4 consecutive years, heifers and steers (average n = 239) were randomly assigned to 1 of 4 treatments: (1) low input, low stocking density, and no fertilizer or distillers grains supplementation (LOW); (2) high stocking density and no fertilizer with distillers grains supplementation (DDGS); (3) high stocking density and 90 kg of nitrogen/ha with no distillers grains supplementation (NFERT); (4) high stocking density, 90 kg of nitrogen/ha, and 39 kg of phosphorus/ha with no distillers grains supplementation (NPFERT). Cattle grazed in the pastures from mid-May to mid-September each year, except for 2011, when the experiment ended in July due to lack of forage. Data were analyzed using a linear model with fixed effects of treatment, year, and treatment × year (R software). Nitrogen use efficiency (retained/inputs) was affected by a treatment × year interaction, where LOW had the greatest efficiency in all years and DDGS was greater than NFERT and NPFERT in all years except 2012, with NFERT and NPFERT being not different in all years. The estimated total carbon equivalent emissions were greater for DDGS, NFERT, and NPFERT than LOW, but the carbon footprint (kg CO2eq/kg weight gain) was lesser for LOW and DDGS, which were not different, than NFERT and NPFERT, which were also not different. Replacing nitrogen fertilizer with dried distiller’s grains improved the cattle performance and the efficiency of resource use, and could be a viable economic alternative to traditional systems

Surface Microbiology of the iPad Tablet Computer and the Potential to Serve as a Fomite in Both Inpatient Practice Settings as Well as Outside of the Hospital Environment

<div><p>Background</p><p>The use of tablet computers and other touch screen technology within the healthcare system has rapidly expanded. It has been reported that these devices can harbor pathogens in hospitals; however, much less is known about what pathogens they can harbor when used outside the hospital environment compared to hospital practice.</p><p>Methods</p><p>Thirty iPads belonging to faculty with a variety of practice settings were sampled to determine the presence and quantity of clinically-relevant organisms. Flocked nylon swabs and neutralizer solution were used to sample the surface of each iPad. Samples were then plated on a variety of selective agars for presence and quantity of selected pathogens. In addition, faculty members were surveyed to classify the physical location of their practice settings and usage patterns. Continuous variables were compared via an unpaired Student's <i>t</i> test with two-tailed distribution; categorical variables were compared with the Fisher's exact test.</p><p>Results</p><p>Of the iPads sampled, 16 belonged to faculty practicing within a hospital and 14 belonged to a faculty member practicing outside a hospital. More faculty within the hospital group used their iPads at their practice sites (78.6% vs. 31.3%; p = 0.014) and within patient care areas (71.4% vs. 18.8%; p = 0.009) than the non-hospital group. There were no differences in the presence, absence, or quantity of, any of the pathogens selectively isolated between groups. Problematic nosocomial pathogens such as methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), vancomycin-resistant enterococci (VRE), and <i>P. aeruginosa</i> were isolated from both hospital and non-hospital faculty iPads.</p><p>Conclusions</p><p>Gram positive and Gram negative organisms were recovered from the surfaces of iPads regardless of practice setting; these included problematic multidrug-resistant pathogens like MRSA, VRE, and <i>Pseudomonas aeruginosa</i>. Healthcare personnel in all settings should be aware of the potential for tablet computers to serve as a nidus for microorganism transmission.</p></div

Pathogen recovery from various selective media.

<p>All quantities listed are in log CFU/mL organisms recovered from the respective selective media used to isolate the organisms as described in methods.</p><p>*Levine pink/colorless colonies identified non-lactose fermenting <i>Salmonella</i> spp., <i>Shigella</i> spp., and <i>Proteus</i> spp., as per package insert.</p>#<p>Levine blue/black colonies identified <i>Enterobacter</i> spp. or <i>Klebsiella</i> spp., as per package insert.</p>‡<p>All means were only calculated for devices with organism growth.</p><p>Pathogen recovery from various selective media.</p