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OBJECTIVES: Mortality rates in intubated coronavirus disease 2019 patients remain markedly elevated. Some patients develop sudden refractory hypercapnia and hypoxemia not explained by worsening pulmonary parenchymal disease. This case series highlights clinical findings and management of coronavirus disease 2019 patients with refractory hypercapnia despite maximal/optimal ventilatory support. Hypercapnia could not be explained by worsening lung disease or other common factors, and thus, a pulmonary vascular etiology was suggested. The pillars of management were targeted to improve pulmonary vascular patency via aggressive anticoagulation and support right ventricular function. DATA SOURCES: Four consecutive patients with confirmed coronavirus disease 2019 infection with sudden hypercapnia and hypoxemia were included. DATA SYNTHESIS: There was sequential development of: 1) severe hypercapnia attributable to marked elevation of dead space without radiographic changes; 2) concomitant coagulopathy manifest by an increase in d-dimer levels; 3) progressive shunt with consequent hypoxemia; and 4) right ventricular dysfunction. Management included extracorporeal Co2 removal, direct thrombin inhibition, pulmonary vasodilators, and inotropic support. Marked improvement in Pao2 allowed reduction in Fio2 in all patients, extracorporeal Co2 removal was discontinued in three patients over the ensuing 3 weeks, and one patient was discharged home. CONCLUSIONS: We speculate that thromboinflammation with pulmonary microvasculature occlusion leads to a sudden increase in dead space and shunt resulting in severe hypercapnia and hypoxemia in coronavirus disease 2019 patients. Early identification of these physiologic and clinical biomarkers could trigger the institution of therapies aiming to reverse the hypercoagulable state and support right ventricular function.

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Nanoparticles (NPs) protected with a ligand monolayer hold promise for a wide variety of applications, from photonics and catalysis to drug delivery and biosensing. Monolayers that include a mixture of ligand types can have multiple chemical functionalities and may also self-assemble into advantageous patterns. Previous work has shown that both chemical and length mismatches among these surface ligands influence phase separation. In this work, we examine the interplay between these driving forces, first by using our previously-developed configurationally-biased Monte Carlo (CBMC) algorithm to predict, then by using our matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) technique to experimentally probe, the surface morphologies of a series of two-ligand mixtures on the surfaces of ultrasmall silver NPs. Specifically, we examine three such mixtures, each of which has the same chemical mismatch (consisting of a hydrophobic alkanethiol and a hydrophilic mercapto-alcohol), but varying degrees of chain-length mismatch. This delicate balance between chemical and length mismatches provides a challenging test for our CBMC prediction algorithm. Even so, the simulations are able to quantitatively predict the MALDI-MS results for all three ligand mixtures, while also providing atomic-scale details from the equilibrated ligand structures, such as patch sizes and co-crystallization patterns. The resulting monolayer morphologies range from randomly-mixed to Janus-like, demonstrating that chain-length modifications are an effective way to tune monolayer morphology without needing to alter chemical functionalities.

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Detection of monolayer morphology on nanoparticles smaller than 10 nm has proven difficult with traditional visualization techniques. Here matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) is used in conjunction with atomistic simulations to detect the formation of Janus-like monolayers on noble metal nanoparticles. Silver metal nanoparticles were synthesized with a monolayer consisting of dodecanethiol (DDT) and mercaptoethanol (ME) at varying ratios. The nanoparticles were then analyzed using MALDI-MS, which gives information on the local ordering of ligands on the surface. The MALDI-MS analysis showed large deviations from random ordering, suggesting phase separation of the DDT/ME monolayers. Atomistic Monte Carlo (MC) calculations were then used to simulate the nanoscale morphology of the DDT/ME monolayers. In order to quantitatively compare the computational and experimental results, we developed a method for determining an expected MALDI-MS spectrum from the atomistic simulation. Experiments and simulations show quantitative agreement, and both indicate that the DDT/ME ligands undergo phase separation, resulting in Janus-like nanoparticle monolayers with large, patchy domains.

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Patients with primary or metastatic brain tumors are at increased risk of developing venous thromboses. However, the potential benefit of therapeutic anticoagulation in these patients must be weighed against the deadly complication of intracranial hemorrhage. In this review, we summarize available evidence and recent studies of intracranial bleeding risks in primary and metastatic tumors and the impact of therapeutic anticoagulation. We find that for the majority of primary and treated metastatic brain tumors, the risk of spontaneous bleeding is acceptable and not further increased by careful therapeutic anticoagulation with low molecular weight heparin or direct oral anticoagulants, although thrombocytopenia (platelet count less than 50,000/µL) and other coagulopathies are relative contraindications. Patients with brain metastasis from melanoma, renal cell carcinoma, choriocarcinoma, thyroid carcinoma, and hepatocellular carcinoma have a higher tendency to bleed spontaneously than noted in patients with other malignancies, and thus warrant routine brain imaging and alternative strategies such as inferior vena cava filter placement in the acute setting of venous thromboembolism before consideration of therapeutic anticoagulation. IMPLICATIONS FOR PRACTICE: Malignant gliomas are associated with increased risks of both venous thromboses and intracranial hemorrhage, but the additional bleeding risk associated with therapeutic anticoagulation appears acceptable, especially after treatment of primary tumors. Most patients with treated brain metastasis have a low risk of intracranial hemorrhage associated with therapeutic anticoagulation, and low molecular weight heparin is currently the preferred agent of choice. Patients with untreated brain metastasis from melanoma, renal cell carcinoma, thyroid cancer, choriocarcinoma, and hepatocellular carcinoma have a higher propensity for spontaneous intracranial bleeding, and systemic anticoagulation may be contraindicated in the acute setting of venous thromboembolism.

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Silver nanoparticles with mixed ligand self-assembled monolayers were synthesized from dodecanethiol and another ligand from a homologous series of alkanethiols (butanethiol, pentanethiol, heptanethiol, octanethiol, nonanethiol, decanethiol, undecanethiol, or dodecanethiol[D25]). These were hypothesized to exhibit ligand phase separation that increases with degree of physical mismatch between the ligands based on the difference in the number of carbons in the two ligands. Dodecanethiol/dodecanethiol[D25] was expected to exhibit minimal phase separation as the ligands have only isotopic differences, while dodecanethiol/butanethiol was hypothesized to exhibit the most phase separation due to the difference in chain length. Phase separation of all other ligand mixtures was expected to fall between these two extremes. Matrix-assisted laser desorption ionization (MALDI) mass spectroscopy provided a value for ligand phase separation by comparison with a binomial (random) model and subsequent calculation of the sum-of-squares error (SSR). These nanoparticle systems were also modeled using the Scheutjens and Fleer self-consistent mean-field theory (SCFT), which determined the most thermodynamically favorable arrangement of ligands on the surface. From MALDI, it was found that dodecanethiol/dodecanethiol[D25] formed a well-mixed monolayer with SSR = 0.002, and dodecanethiol/butanethiol formed a microphase separated monolayer with SSR = 0.164; in intermediate dodecanethiol/alkanethiol mixtures, SSR increased with increasing ligand length difference as expected. For comparison with experiment, an effective SSR value was calculated from SCFT simulations. The SSR values obtained by experiment and theory show good agreement and provide strong support for the validity of SCFT predictions of monolayer structure. These approaches represent robust methods of characterization for ligand phase separation on silver nanoparticles.

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MALDI mass-spectrometry measurements are combined with self-consistent mean-field (SCF) calculations to detect and predict ligand phase separation on Ag nanoparticles. The experimental and theoretical techniques complement each other by enabling quantification of the nearest-neighbor distribution of a ligand mixture in a monolayer shell. By tracking a characteristic metallic fragment family, analysis of a MALDI spectrum produces a frequency distribution corresponding to specific ligand patterning. Inherent to the SCF calculation is the enumeration of local interactions that dictate ligand assembly. Interweaving MALDI and SCF facilitates a comparison between the experimentally and theoretically derived frequency distributions as well as their deviation from a well-mixed state. Thus, we combine these techniques to detect and predict phase separation in monolayers that mix uniformly or experience varying degrees of de-mixing, including microphase separation and stripe formation. Definition of MALDI removed as this is a commonly recognized technique.

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Using rheo-optical techniques, we investigated the impact of interfacial wetting of symmetric diblock copolymers (BCPs) on the coalescence and aggregation of polydimethylsiloxane (PDMS) droplets in immiscible polyethylene-propylene (PEP) homopolymers. Anionic polymerization was used to synthesize well-defined matrix homopolymers and symmetric 16 kg/mol-to-16 kg/mol PDMS-b-PEP diblock copolymers with low polydispersity (PDI ≈ 1.02) as characterized with size exclusion chromatography and nuclear magnetic resonance spectroscopy. Blends were formulated to match the viscosities between the droplets and the matrix. Moreover, molecular weights of these components were varied to ensure that the inner block of the copolymer inside the droplet was collapsed and dry, whereas the outer block of the copolymer outside of the droplet was stretched and wet. Droplet breakup and coalescence as well as interfacial tensions were measured using rheo-optical experiments with Linkam shearing stage and an optical microscope. Subsequent to droplet breakup at high shear rates, we found that the BCPs mitigated shear-induced coalescence at lower shear rates. Based on surface tension measurements, the stretching of the BCP increased in lower molecular weight matrices, causing the droplet surface to saturate at lower coverage in line with theoretical predictions. Droplet aggregation was detected with further reductions in shear rate, which was attributed to the dewetting or the expulsion of the matrix from a saturated brush. Ultimately, the regions of droplet coalescence and aggregation were scaled by balancing the forces of shear with those due to the attraction between BCP-coated droplets.

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To determine the quality and completeness of the list of home medications documented by nurses using a codified process, authors conducted a comparative study of home medications using a non-codified and codified process for documentation of required data fields including drug, dose, route of administration, frequency, and schedule. Each documented home medication (DHM) was evaluated based on the ability to convert to an inpatient medication order. The home medication was classified as non-convertible if one or more of the required data fields were missing, inaccurate, or incomplete. The study compared 176 patients with 1618 DHM in the non-codified group to 94 patients with 646 DHM in the codified group. All DHM could be converted to inpatient orders for 70% of the patients in the codified group compared with 42% in the non-codified group. Based on each DHM, the codified process resulted in 92% of the DHM being able to convert to inpatient orders compared with 82% for the non-codified process. Authors conclude that use of a codified process to document home medications has the potential to increase the number of complete drug entries and in the number of patients with a DHM list in which all of the medication entries have all of the dosing information.

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Pulmonary involvement and skin involvement are rare complications of plasma cell neoplasms. Here we describe what may be the first reported case of a patient with relapse in both of these sites following autologous peripheral blood stem cell transplantation.

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We quantified the impact of the carbon spacer length (CSL) of immobilized alkoxysilanes initiators on grafting poly(methyl methacrylate) (PMMA) from the surfaces of monodisperse silica nanoparticles. PMMA was grafted using surface-initiated atom transfer radical polymerization (SI-ATRP), a facile technique to produce well-controlled polymer brushes. The polymerizations were carried out in environmentally friendly 4:1 (v/v) methanol-water solutions at room temperature. Monoethoxysilane initiators of 3, 11, and 15 carbon spacer lengths were synthesized and characterized with (1)H NMR and (13)C NMR. The initiators were then used to modify the surfaces of monodisperse silica nanoparticles in methyl isobutyl ketone, producing dense initiator monolayers with site densities between 1.8-3.6 initiators/nm(2). PMMA was subsequently grafted from the functionalized nanoparticles using both CuCl and CuBr catalysts. We found that polymerizations performed with CuBr were uncontrolled, whereas those with CuCl were controlled. PMMA graft densities ranged between 0.10-0.43 polymers/nm(2), which increased with the initiator carbon spacer length (CSL). Interestingly, longer CSLs make nanoparticle surfaces hydrophobic, causing nanoparticle aggregation in methanol-water solutions. Our results indicate that surface hydrophobicity correlates to increases in PMMA graft density through the adsorption of hydrophobic MMA monomers on initiators with longer CSLs. Thus, to augment PMMA graft densities, a subtle balance must be struck between enabling particle stability and increasing MMA adsorption in methanol-water solutions.

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Using dynamic light scattering, mechanical rheometry, and visual observation, the static wetting behavior of PDMS-grafted silica spheres (PDMS-g-silica) in PDMS melts is related to their rheology. A phase diagram is mapped out for a constant grafted chain length as a function of grafting density and free polymer chain length. The transition between stable and aggregated regions is determined optically and with dynamic light scattering. It is associated with a first-order wetting transition. In the stable region Newtonian behavior is observed for semidilute suspensions. The hydrodynamic brush thicknesses, deduced from viscosity measurements, correspond closely to values obtained from self-consistent field calculations for the various parameter values. At the transition, the brush collapses suddenly and shear-thinning and thixotropy appear. The rheology indicates a degree of aggregation that increases with increasing length of the free polymer, as suggested by the theory.

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The objective of this retrospective study was to determine the optimal initial antibiotic regimen for hospital-acquired pneumonia using the frequency and sensitivity of Gram negative microorganisms found in sputum cultures. An antibiogram was constructed and compared with the hospital intensive care unit (ICU) antibiogram. The results yielded 191 microorganisms. The study-generated antibiogram showed that the highest percent susceptible antibiotics for all Gram-negative microorganisms were imipenem (75%) and amikacin (84%). Considering only Pseudomonas aeruginosa, the study-generated antibiogram and the hospital ICU antibiogram showed similar results, piperacillin and amikacin (86% and 82%, respectively, vs 91% and 85%, P = nonsignificant for both). The optimal empiric antibiotic regimen in the surgical ICU is different if directed against all possible microorganisms as opposed to the most prevalent microorganism P aeruginosa. Determining initial empiric antibiotic therapy using an ICU and culture-type specific antibiogram would result in a greater likelihood that more patients would receive adequate initial antibiotic therapy.

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BACKGROUND: People with multiple sex partners tend to forget a significant proportion when recalling them. METHODS: Randomized trial of supplementary interviewing techniques during routine partner notification contact interviews for chlamydia, gonorrhea, and syphilis in Colorado Springs, CO. Cases with multiple sex partners in the last 3 months (n = 123) participated. Interviewers prompted nonspecifically and read back the list of elicited partners after cases recalled partners on their own. We then randomly assigned cases to receive 1 of 3 sets of recall cues: (1) an experimental set of cues consisting of locations where people meet partners, role relationships, network ties, and first letters of names; (2) another experimental set including common first names; and (3) control cues referring to individual characteristics (e.g., physical appearance). RESULTS: Nonspecific prompting and reading back the list each increased the number of additional partners elicited and located by 3% to 5% on average. On average, the combined location/role/letter/network cues elicited more additional partners (0.57) than did the first-name (0.29) and individual characteristics (0.28) cues. The location and first-name cues were the most effective in eliciting located partners. The supplementary techniques increased the number of new cases found by 12% and, importantly, identified branches of the sexual network that would not otherwise have been discovered. CONCLUSION: Elicitation of sex partners can be enhanced in contact interviews with simple interviewing techniques, resulting in improved network ascertainment and sexually transmitted disease case finding.

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OBJECTIVE: To provide a critical and comprehensive review of the literature, specifically case reports and observational studies used to support the concept of cross-reactivity between sulfonylarylamines and non-sulfonylarylamines. DATA SOURCES: A list of medications was formulated from several different review articles. A MEDLINE/PubMed search was conducted (1966-March 2004) using the individual medications and the MeSH terms of drug hypersensitivity/etiology, sulfonamides/adverse effects, and/or cross-reaction. STUDY SELECTION AND DATA EXTRACTION: A critical review of the methodology and conclusions for each article found in the search was conducted. The manufacturer's package insert (MPI) for each drug was examined for a statement concerning possible cross-reactivity in patients with a sulfonamide allergy. If indicated, the manufacturers were contacted to obtain any clinical data supporting the statement. DATA SYNTHESIS: A total of 33 medications were identified. Seventeen (51.5%) of the MPIs contained statements of varying degrees concerning use in patients with a "sulfonamide" allergy; 21 case series, case reports, and other articles were found. CONCLUSIONS: After a thorough critique of the literature, it appears that the dogma of sulfonylarylamine cross-reactivity with non-sulfonylarylamines is not supported by the data. While many of the case reports on the surface support the concept of cross-reactivity, on closer examination the level of evidence in many of the cases does not conclusively support either a connection or an association between the observed cause and effect.

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