Use of bivalirudin after initial heparin management among adult patients on long-term venovenous extracorporeal support as a bridge to lung transplant: A case series.

A growing body of evidence supports the use of bivalirudin as an alternative to unfractionated heparin (UFH) for the prevention of thrombotic events in patients on venovenous (VV) extracorporeal membrane oxygenation (ECMO). However, data in patients bridged to lung transplantation are limited. In this case series, we describe the outcomes of six patients who were transitioned from UFH to bivalirudin during their course of VV ECMO support as a bridge to lung transplantation. All six patients were on VV ECMO support until transplant, with a median duration of 73 days. Bivalirudin demonstrated a shorter time to first therapeutic activated thromboplastin time (aPTT) level. Additionally, time in therapeutic range was longer while patients were receiving bivalirudin compared to UFH (median 92.9% vs. 74.6%). However, major bleeding and thrombotic events occurred while patients were receiving either anticoagulant. Based on our experience, bivalirudin appears to be a viable option for anticoagulation in VV ECMO patients bridged to lung transplantation. Larger studies evaluating the optimal anticoagulation strategy in patients bridged to transplant are needed.

A case series analysis of bicarbonate-based purge solution administration via Impella ventricular assist device.

PURPOSE: The Impella device historically required a heparin-based purge solution to reduce the risk of biomaterial deposition to maintain pump function. In April 2022, the Food and Drug Administration approved utilization of bicarbonate-based purge solutions (BBPS) as an alternative to heparin for patients who are intolerant to heparin or in whom heparin is contraindicated. The purpose of this case series is to report patient outcomes of Impella support with BBPS use at our institution. SUMMARY: Eighteen patients who received BBPS via the Impella CP or Impella 5.5 device were included in our review. Patients were included if they had BBPS administration for greater than 24 hours. All patients were followed for 72 hours after cessation of BBPS. Indications for BBPS were coagulopathy (n = 5, 28%), suspected HIT (n = 2, 11%), confirmed HIT (n = 1, 6%), and major bleeding (n = 10, 56%). Three patients (17%) experienced an Impella complication while on BBPS. One patient required pump exchange, one required removal of the Impella device, and one received alteplase for suspected purge block. Of these, two patients experienced complications greater than 21 days into BBPS therapy. CONCLUSION: This case series adds to the literature describing clinical outcomes for patients on Impella support with BBPS. While BBPS offers a viable option for the management of patients on Impella devices who are unable to tolerate heparin-based purge solutions, further data is needed to determine the longevity of the Impella device with BBPS to minimize risk of Impella complications.

Comparison of Sedation and Analgesia Requirements in Patients With SARS-CoV-2 Versus Non-SARS-CoV-2 Acute Respiratory Distress Syndrome on Veno-Venous ECMO.

BACKGROUND: Increased analgosedation requirements have been described in patients with acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO) support due to unique pharmacokinetic challenges. There is a paucity of data comparing sedation requirements in patients on ECMO for ARDS secondary to SARS-CoV-2 versus other etiologies of respiratory failure. OBJECTIVE: To compare sedation and analgesia requirements in adult patients with SARS-CoV-2 versus non-SARS-CoV-2 ARDS requiring veno-venous (VV) ECMO support. METHODS: We performed a retrospective cohort study of adult patients receiving sedation and analgesia on VV-ECMO support. Patients were excluded if cannulated at an outside hospital for greater than 24 hours, expired within 48 hours of ECMO cannulation, or received neuromuscular blocking agents for greater than 7 consecutive days following ECMO cannulation. RESULTS: We evaluated 108 patients on VV-ECMO support, including 44 with non-SARS-CoV-2 ARDS and 64 with SARS-CoV-2 ARDS. The median daily dexmedetomidine requirements were significantly higher in the SARS-CoV-2 cohort (16.7 vs 13.4 mcg/kg/day, P = 0.03), while the median propofol daily requirements were significantly higher in the non-SARS-CoV-2 cohort (40.3 vs 53.5 mg/kg/day, P < 0.01). There was no difference in daily requirements of opioids, benzodiazepines, and ketamine between groups. Use of adjunct agents to facilitate weaning was significantly higher in the SARS-CoV-2 cohort (78.1% vs 43.2%, P < 0.01). CONCLUSION AND RELEVANCE: Patients with ARDS on VV-ECMO support require multiple analgosedative agents with concomitant use of nonparenteral adjunct agents. Further studies are needed to evaluate optimal analgosedation strategies in patients on ECMO support.

Extensively Drug-Resistant Myroides odoratus in Critically Ill Patients: A Case Series and Literature Review.

The bacterial genus Myroides, like other members of the Flavobacteriaceae family, consists of aerobic, non-motile, Gram-negative bacilli. Myroides spp. is considered predominantly opportunistic pathogens as, historically, most documented infections have been in immunocompromised individuals. Along with advancements in molecular assay testing, there are growing reports of clinically relevant Myroides spp. infections in immunocompetent individuals. These organisms display broad antimicrobial resistance, and while research into their mechanisms of resistance is progressing, genetic testing has revealed metallo-ß-lactamases present in their genome. The sporadic identification of Myroides spp. and ongoing clarification of resistance patterns make empiric treatment difficult. This report documents two cases of extensively drug-resistant Myroides odoratus isolated from critically ill but otherwise immunocompetent patients followed by a review of available literature on Myroides spp. antibiotic sensitivities. Our findings indicate that minocycline and moxifloxacin have the highest documented in vitro activity against Myroides spp.

Impact of Established and Emerging Software Tools on the Metabolite Identification Landscape.

Scientists' ability to detect drug-related metabolites at trace concentrations has improved over recent decades. High-resolution instruments enable collection of large amounts of raw experimental data. In fact, the quantity of data produced has become a challenge due to effort required to convert raw data into useful insights. Various cheminformatics tools have been developed to address these metabolite identification challenges. This article describes the current state of these tools. They can be split into two categories: Pre-experimental metabolite generation and post-experimental data analysis. The former can be subdivided into rule-based, machine learning-based, and docking-based approaches. Post-experimental tools help scientists automatically perform chromatographic deconvolution of LC/MS data and identify metabolites. They can use pre-experimental predictions to improve metabolite identification, but they are not limited to these predictions: unexpected metabolites can also be discovered through fractional mass filtering. In addition to a review of available software tools, we present a description of pre-experimental and post-experimental metabolite structure generation using MetaSense. These software tools improve upon manual techniques, increasing scientist productivity and enabling efficient handling of large datasets. However, the trend of increasingly large datasets and highly data-driven workflows requires a more sophisticated informatics transition in metabolite identification labs. Experimental work has traditionally been separated from the information technology tools that handle our data. We argue that these IT tools can help scientists draw connections via data visualizations and preserve and share results via searchable centralized databases. In addition, data marshalling and homogenization techniques enable future data mining and machine learning.

How to approach the study of syndromes in macroevolution and ecology.

Syndromes, wherein multiple traits evolve convergently in response to a shared selective driver, form a central concept in ecology and evolution. Recent work has questioned the existence of some classic syndromes, such as pollination and seed dispersal syndromes. Here, we discuss some of the major issues that have afflicted research into syndromes in macroevolution and ecology. First, correlated evolution of traits and hypothesized selective drivers is often relied on as the only evidence for adaptation of those traits to those hypothesized drivers, without supporting evidence. Second, the selective driver is often inferred from a combination of traits without explicit testing. Third, researchers often measure traits that are easy for humans to observe rather than measuring traits that are suited to testing the hypothesis of adaptation. Finally, species are often chosen for study because of their striking phenotypes, which leads to the illusion of syndromes and divergence. We argue that these issues can be avoided by combining studies of trait variation across entire clades or communities with explicit tests of adaptive hypotheses and that taking this approach will lead to a better understanding of syndrome-like evolution and its drivers.

Approach to Sedation and Analgesia in COVID-19 Patients on Venovenous Extracorporeal Membrane Oxygenation.

OBJECTIVE: To describe clinically pertinent challenges of managing sedation in COVID-19 patients on venovenous extracorporeal membrane oxygenation (VV-ECMO) and describe considerations for enhanced safety and efficacy of pharmacological agents used. DATA SOURCES: A PubMed search was performed using the following search terms: ECMO, ARDS, sedation, COVID-19, coronavirus, opioids, analgesia, fentanyl, hydromorphone, morphine, oxycodone, methadone, ketamine, propofol, dexmedetomidine, clonidine, benzodiazepines, midazolam, lorazepam, and diazepam. STUDY SELECTION AND DATA EXTRACTION: Relevant clinical and pharmacokinetic studies were considered. All studies included were published between January 1988 and March 2021. DATA SYNTHESIS: Patients with acute respiratory distress syndrome secondary to COVID-19 may progress to requiring VV-ECMO support. Agents frequently used for sedation and analgesia in these patients have been shown to have significant adsorption to ECMO circuitry, leading to possible diminished clinical efficacy. Use of hydromorphone-based analgesia has been associated with improved clinical outcomes in patients on VV-ECMO. However, safety and efficacy regarding use of other agents in this patient population remains an area of further research. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review addresses clinical challenges associated with sedation management in COVID-19 patients requiring VV-ECMO support and provides potential strategies to overcome these challenges. CONCLUSIONS: Historically, sedation and analgesia management in patients requiring ECMO support have posed a challenge for bedside clinicians given the unique physiological and pharmacokinetic changes in this patient population. A multimodal strategy to managing analgesia and sedation should be used, and the use of enteral agents may play a role in reducing parenteral agent requirements.

Extended Perspective Shift and Discourse Economy in Language Processing.

Research spanning linguistics, psychology, and philosophy suggests that speakers and hearers are finely attuned to perspectives and viewpoints that are not their own, even though perspectival information is not encoded directly in the morphosyntax of languages like English. While some terms seem to require a perspective or a judge for interpretation (e.g., epithets, evaluative adjectives, locational PPs, etc.), perspective may also be determined on the basis of subtle information spanning multiple sentences, especially in vivid styles of narrative reporting. In this paper, I develop an account of the cues that are involved in evaluating and maintaining non-speaker perspectives, and present an economy-based discourse processing model of perspective that embodies two core principles. First, perspectives are subject to a "speaker-default," but may shift to a non-speaker perspective if sufficient contextual cues are provided. Second, the processor follows the path of least resistance to maintaining perspective, opting to maintain the current perspective across sentences as long as the shifted perspective continues to be coherent. The predictions of the model are tested in a series of offline and online studies, manipulating the form of an attitude report and the tense of the sentence that follows. Implications for processing perspective and viewpoint in speech and narrative forms are explored.

Contextual constraint and lexical competition: Revisiting biased misperception during reading.

In identifying and accessing lexical items while comprehending text, readers must rapidly select a word from visually similar words before integrating it into a sentence. It has been proposed that readers are likely to misperceive a low frequency word as a highly frequent orthographically similar alternative, particularly when the alternative is supported by previous context (Gregg & Inhoff, 2016; Perea & Pollatsek, 1998; Pollatsek, Perea, & Binder, 1999; Slattery, 2009). In such cases, the misperception may not be corrected until the reader encounters incongruent information. However, many of these studies place incongruent text directly after the critical word, confounding whether readers regress backward in text to resolve their misperception or to halt forward text progression in order resolve a lexical level conflict between the word form and its competitor. In 3 eye tracking while reading experiments, we adapted materials from previous studies to include a postcritical spillover region to address this possibility. Two of these experiments were designed to permit an ex-Gaussian analysis of the distribution of first pass reading prior to disambiguating information. The evidence suggests that postlexical competition-inhibition between orthographically similar forms can delay forward movement of the eyes as a competitor is inhibited. The possibility that misperception and postlexical competition-inhibition arise from the same set of mechanisms is discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Viable Hemostasis Obtained With Prothrombin Complex Concentrate in Patients Who Refuse Standard Allogeneic Blood Transfusion and Undergo Complex Cardiac Surgery: A Case Series.

Human 4-factor prothrombin complex concentrate (4F-PCC) may reduce blood loss during surgery. This case series described perioperative outcomes among 9 patients who refused standard allogeneic blood transfusion, underwent complex cardiac surgery with aortic involvement, and received intraoperative 4F-PCC. Additional intraoperative cointerventions included protamine (n = 9), aminocaproic acid (n = 8), fibrinogen concentrate (n = 6), desmopressin (n = 6), factor VIIa (n = 2), and tranexamic acid (n = 1). Outcomes included postoperative death (n = 1), major postoperative bleeding (n = 1), deep vein thrombosis (n = 2), and ischemic stroke (n = 1). When standard allogeneic blood transfusion is refused, viable hemostasis can be obtained using 4F-PCC during complex cardiac surgeries with a high risk of bleeding.

The Liver That Cured Christmas: Case Report of Orthotopic Liver Transplant in a Patient with Hemophilia B.

Herein, we discuss a case of a 39-year-old male with hemophilia B, who developed end-stage liver disease secondary to nonalcoholic steatohepatitis, that underwent orthotopic liver transplantation (OLT) as a curative means for his liver disease and coagulation disorder. Existing case reports have demonstrated favorable outcomes in patients outside of the United States who received continuous infusions of recombinant factor IX replacement in the perioperative setting after liver transplant. Given limitations in the stability of the recombinant factor IX products in the United States, a dosing strategy was comprised of once daily bolus dosing to achieve satisfactory factor IX levels. Within 48 hours of initial surgery, the patient had sustained factor IX levels above 70% of normal and the patient required no further dosing of factor IX products to date. This strategy helped facilitate less frequent dosing as well as achieved targeted factor levels while synthetic function of the transplanted liver recovered.

Evaluation of postoperative clinical outcomes in Jehovah's Witness patients who receive prothrombin complex concentrate during cardiac surgery.

BACKGROUND: Patients who refuse allogeneic blood transfusions (alloBT) on the basis of religious doctrine, such as Jehovah's Witnesses (JWs), can pose a challenge when undergoing surgical procedures. During cardiac surgery, special considerations regarding surgical techniques and blood loss minimization strategies can lead to improved outcomes. Limited literature exists to guide the use of four-factor prothrombin complex concentrate (4PCC) in this patient population undergoing cardiac surgery. STUDY DESIGN AND METHODS: This retrospective, single-center study evaluated the impact of 4PCC on hemoglobin (Hgb) change from baseline to postoperative nadir within a 7-day period among patients who refused alloBT during cardiac surgery. This study identified patients who refused alloBT from January 2011 to June 2017. Multivariable linear regression was used to control for confounding variables to evaluate the effectiveness of 4PCC. RESULTS: During the study timeframe, 79 patients met inclusion criteria, all of whom identified as JWs, and underwent cardiac surgery. Of these, 19 received intraoperative 4PCC. Multivariable linear regression found no difference in Hgb change in patients who received 4PCC vs those who did not. No significant differences were found in mortality, thromboembolic complications, or in-hospital postoperative events. CONCLUSIONS: In JWs undergoing cardiac surgery who refuse alloBT, intraoperative use of 4PCC was not associated with a difference in Hgb change within 7 days postoperatively when adjusting for confounding variables. In the event of excessive blood loss, the utilization of 4PCC may provide a viable option in JW patients who undergo cardiac surgery where few options exist to mitigate blood loss.

Correlate not optional: PP sprouting and parallelism in "much less" ellipsis.

Clauses that are parallel in form and meaning show processing advantages in ellipsis and coordination structures (Frazier et al. 1984; Kehler 2000; Carlson 2002). However, the constructions that have been used to show a parallelism advantage do not always require a strong semantic relationship between clauses. We present two eye tracking while reading studies on focus-sensitive coordination structures, an understudied form of ellipsis which requires the generation of a contextually salient semantic relation or scale between conjuncts. However, when the remnant of ellipsis lacks an overt correlate in the matrix clause and must be "sprouted" in the ellipsis site, the relation between clauses is simplified to entailment. Instead of facilitation for sentences with an entailment relation between clauses, our online processing results suggest that violating Parallelism is costly, even when doing so could ease the semantic relations required for interpretation.

Sodium Methyl Carbonate as an Effective C1 Synthon. Synthesis of Carboxylic Acids, Benzophenones, and Unsymmetrical Ketones.

Reported is the synthesis of carboxylic acids, symmetrical ketones, and unsymmetrical ketones with selectivity achieved by exploiting the differential reactivity of sodium methyl carbonate with Grignard and organolithium reagents.

Frequency of troponin elevations in patients with influenza infection during the 2017-2018 influenza season.

BACKGROUND: With the increased number of influenza cases observed during the 2017 - 2018 season, patients may be at a greater risk of cardiac related complications as a sequela of viral illness. We described the frequency of troponin elevations in patients with influenza infection during the 2017 - 2018 influenza season. METHODS: This was a retrospective, single-center observational study. All patients aged 18 years or older and had laboratory confirmed influenza viral infection were included in the study. Troponins were considered elevated if greater than 0.3 ng/mL. Electronic health records were reviewed for demographics, laboratory values, coronary artery disease history, electrocardiography, echocardiography results, and incidence of inpatient mortality. RESULTS: A total of 1,131 patients had lab confirmed influenza infection. Majority of the influenza strains were influenza A, 76.2% (n = 863), and the rest of the influenza strains comprised of influenza B, 23.8% (n = 270). Thirty three (2.9%) patients had elevation of troponin levels greater than 0.3 ng/mL. Most of the patients with elevated troponin levels had influenza A infection (90.9%, n = 30), of which H3 subtype was the most common (48.5%, n = 16). Fifteen patients (45.5%) had a myocardial infarction, 20 (60.6%) had left ventricular abnormalities visualized on echocardiogram, and four (12.1%) died while inpatient. CONCLUSIONS: Our results describe the frequency of troponin elevations in patients with influenza infection at our institution during the 2017 - 2018 influenza season.

Zero-Adjective Contrast in Much-less Ellipsis: The Advantage for Parallel Syntax.

This paper explores the processing of sentences with a much less coordinator (I don't own a pink hat, much less a red one). This understudied ellipsis sentence, one of several focus-sensitive coordination structures, imposes syntactic and semantic conditions on the relationship between the correlate (a pink hat) and remnant (a red one). We present the case of zero-adjective contrast, in which an NP remnant introduces an adjective without an overt counterpart in the correlate (I don't own a hat, much less a red one). Although zero-adjective contrast could in principle ease comprehension by limiting the possible relationships between the remnant and correlate to entailment, we find that zero-adjective contrast is avoided in production and taxing in online processing. Results from several studies support a processing model in which syntactic parallelism is the primary guide for determining contrast in ellipsis structures, even when violating parallelism would assist in computing semantic relationships.

Information Structure Preferences in Focus-Sensitive Ellipsis: How Defaults Persist.

We compare the roles of overt accent and default focus marking in processing ellipsis structures headed by focus-sensitive coordinators (such as Danielle couldn't pass the quiz, let alone the final/Kayla). In a small auditory corpus study of radio transcripts, we establish that such structures overwhelmingly occur with contrastive pitch accents on the correlate and remnant ( the quiz and the final, or Danielle and Kayla), and that there is a strong bias to pair the remnant with the most local plausible correlate in production. In two auditory naturalness ratings experiments, we observe that marking a non-local correlate with contrastive pitch accent moderates, but does not fully overturn, the bias for local correlates in comprehension. We propose that the locality preference is due to a sentence-final default position for sentence accent, and that auditory processing is subject to "enduring focus," in which default positions for focus continue to influence the focus structure of the sentence even in the presence of overt accents. The importance of these results for models of auditory processing and of the processing of remnants in ellipsis structures is discussed.

Impact of intraoperative factor concentrates on blood product transfusions during orthotopic liver transplantation.

BACKGROUND: Major bleeding in orthotopic liver transplantation is associated with significant morbidity and mortality. Limited literature exists regarding comparative effectiveness of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation on blood product utilization. STUDY DESIGN AND METHODS: This retrospective, single-institution study evaluated the impact of prothrombin complex concentrate and fibrinogen concentrate on blood product utilization during orthotopic liver transplantation from December 2013 to April 2016. This study included patients age 18 years or older and excluded patients who received simultaneous heart or lung transplantation or did not meet documentation criteria. A propensity score matching technique was used to match patients who were exposed to prothrombin complex concentrate with unexposed patients, at a 2 to 1 ratio, to control for selection bias. RESULTS: During this study, 212 patients received orthotopic liver transplantation with 39 prothrombin complex concentrate exposures. The matched study population included 39 patients who were exposed to prothrombin complex concentrate and 78 unexposed patients. Overall, 84.6% of patients who were exposed to prothrombin complex concentrate also received concomitant fibrinogen concentrate, whereas only 2% of patients in the control group received fibrinogen concentrate. After propensity score matching, no other factors that were included in the model differed significantly or had a standardized mean difference of 0.11 or greater. There was no statistical difference in the utilization of red blood cells or fresh frozen plasma for the exposed group versus the unexposed group after matching (mean ± standard deviation: red blood cell units, 12.4 ± 8.0 units vs. 9.7 ± 5.6 units [p = 0.058]; fresh-frozen plasma units, 10.0 ± 6.3 vs. 12.7 ± 9.7 units [p = 0.119], respectively). CONCLUSION: The intraoperative use of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation did not reduce intraoperative blood product requirements at a single institution.

Keep it local (and final): Remnant preferences in "let alone" ellipsis.

The let alone construction (John can't run a mile, let alone a marathon) differs from standard coordination structures (with and or but) by requiring ellipsis of the second conjunct--for example, a marathon is the remnant of an elided clause [[see text] a marathon]. In support of an ellipsis account, a corpus study of British and American English finds that let alone exhibits a Locality bias, as the second conjunct preferentially contrasts with the nearest lexical item of the same syntactic type. Two self-paced reading studies show that the Locality bias is active during online processing, but must be reconciled with indicators of semantic contrast and discourse information. Further, a sentence-rating study shows that the Locality bias interacts with a Finality bias that favours placing the let alone phrase at the end of a clause, which sometimes necessitates a nonlocal contrast. Together, the results show how a general bias in ellipsis for local contrasts is affected by discourse demands, such as the need for scalar contrast imposed by let alone, thereby offering a window into how possibly divergent syntactic and discourse constraints impact sentence processing.

Biocompatibility of low molecular weight polymers for two-phase partitioning bioreactors.

Two phase partitioning bioreactors (TPPBs) improve the efficiency of fermentative processes by limiting the exposure of microorganisms to toxic solutes by sequestering them into a non-aqueous phase (NAP). A potential limitation of this technology, when using immiscible organic solvents as the NAP, is the cytoxicity that these materials may exert on the microbes. An improved TPPB configuration is one in which polymeric NAPs are used to replace organic solvents in order to take advantage of their low cost, improved handling qualities, and biocompatibility. A recent study has shown that low molecular weight polymers may confer improved solute uptake relative to high molecular weight polymers (i.e., have higher partition coefficients), but it is unknown whether sufficiently low molecular weight polymers may inhibit cell growth. This study has investigated the biocompatibility of a range of low molecular weight polymers, and compared trends in biocompatibility to the well-established "critical log P" concept. This was achieved by determining the biocompatibility of polypropylene glycol polymers over a molecular weight (MW) range of 425-4,000 to Saccharomyces cerevisiae and Pseudomonas putida, two organisms which have been previously used in TPPB systems. The lower MW polymers were shown to have lower average log P values, and showed more cytotoxicity than polymers of the same structure but with higher molecular weight. Since polymers are generally polydisperse (i.e., polymer samples contain a distribution of MWs), removal of the lower MW fractions via water washing was found to result in improved polymer biocompatibility. These results suggest that the critical log P concept remains useful for describing the toxicity of polymeric substances of different MWs, although it is complicated by the presence of the low MW fractions in the polymers arising from polydispersity.