Integrating a Virtual ICU with Cardiac and Cardiovascular ICUs: Managing the Needs of a Complex and High-Acuity Specialty ICU Cohort.

A long-standing shortage of critical care intensivists and nurses, exacerbated by the coronavirus disease (COVID-19) pandemic, has led to an accelerated adoption of tele-critical care in the United States (US). Due to their complex and high-acuity nature, cardiac, cardiovascular, and cardiothoracic intensive care units (ICUs) have generally been limited in their ability to leverage tele-critical care resources. In early 2020, Houston Methodist Hospital (HMH) launched its tele-critical care program called Virtual ICU, or vICU, to improve its ICU staffing efficiency while providing high-quality, continuous access to in-person and virtual intensivists and critical care nurses. This article provides a roadmap with prescriptive specifications for planning, launching, and integrating vICU services within cardiac and cardiovascular ICUs-one of the first such integrations among the leading academic US hospitals. The success of integrating vICU depends upon the (1) recruitment of intensivists and RNs with expertise in managing cardiac and cardiovascular patients on the vICU staff as well as concerted efforts to promote mutual trust and confidence between in-person and virtual providers, (2) consultations with the bedside clinicians to secure their buy-in on the merits of vICU resources, and (3) collaborative approaches to improve workflow protocols and communications. Integration of vICU has resulted in the reduction of monthly night-call requirements for the in-person intensivists and an increase in work satisfaction. Data also show that support of the vICU is associated with a significant reduction in the rate of Code Blue events (denoting a situation where a patient requires immediate resuscitation, typically due to a cardiac or respiratory arrest). As the providers become more comfortable with the advances in artificial intelligence and big data-driven technology, the Cardiac ICU Cohort continues to improve methods to predict and track patient trends in the ICUs.

Defining Vasoplegia Following Durable, Continuous Flow Left Ventricular Assist Device Implantation.

This study aimed to develop a definition of vasoplegia that reliably predicts clinical outcomes. Vasoplegia was evaluated using data from the electronic health record for each 15-minute interval for 72 hours following cardiopulmonary bypass. Standardized definitions considered clinical features (systemic vascular resistance [SVR], mean arterial pressure [MAP], cardiac index [CI], norepinephrine equivalents [NEE]), threshold strategy (criteria occurring in any versus all measurements in an interval), and duration (criteria occurring over multiple consecutive versus separated intervals). Minor vasoplegia was MAP < 60 mm Hg or SVR < 800 dynes⋅sec⋅cm-5 with CI > 2.2 L/min/m2 and NEE ≥ 0.1 µg/kg/min. Major vasoplegia was MAP < 60 mm Hg or SVR < 700 dynes⋅sec⋅cm-5 with CI > 2.5 L/min/m2 and NEE ≥ 0.2 µg/kg/min. The primary outcome was incidence of vasoplegia for eight definitions developed utilizing combinations of these criteria. Secondary outcomes were associations between vasoplegia definitions and three clinical outcomes: time to extubation, time to intensive care unit discharge, and nonfavorable discharge. Minor vasoplegia detected anytime within a 15-minute period (MINOR_ANY_15) predicted the highest incidence of vasoplegia (61%) and was associated with two of three clinical outcomes: 1 day delay to first extubation (95% CI: 0.2 to 2) and 7 day delay to first intensive care unit discharge (95% CI: 1 to 13). The MINOR_ANY_15 definition should be externally validated as an optimal definition of vasoplegia.

At-line high throughput site-specific glycan profiling using targeted mass spectrometry.

Protein post-translational modification (PTM) plays an important role in many biological processes; of which glycosylation is arguably one of the most complex and diverse modifications and is crucial for the safety and efficacy of biotherapeutic proteins. Mass spectrometric characterization of protein glycosylation is well established with clear advantages and disadvantages; on one hand it is precise and information-rich, as well as being relative inexpensive in terms of the reagents and consumables despite the instrumentation cost and, depending on the method, can give site specific information; on the other hand it generally suffers from low throughput, restriction to largely purified samples and is less quantitative, especially for sialylated glycan species. Here, we describe a high throughput, site-specific, targeted mass spectrometric peptide mapping approach to quickly screen/rank candidate production cell lines and culture conditions that give favourable glycosylation profiles directly from conditioned culture media for an Fc-fusion protein. The methodology is fully compatible with automation and combines the speed of 'top-down' mass spectrometry with the site-specific information of 'bottom-up' mass spectrometry. In addition, this strategy can be used for multi-attribute product quality screening/monitoring as an integral part of cell line selection and process development.

Interfacial Adsorption of a Monoclonal Antibody and Its Fab and Fc Fragments at the Oil/Water Interface.

The physical stability of a monoclonal antibody (mAb) solution for injection in a prefilled syringe may in part depend on its behavior at the silicone oil/water interface. Here, the adsorption of a mAb (termed COE-3) and its fragment antigen-binding (Fab) and crystallizable (Fc) at the oil/water interface was measured using neutron reflection. A 1.4 ± 0.1 µm hexadecane oil film was formed on a sapphire block by a spin-freeze-thaw process, retaining its integrity upon contact with the protein solutions. Measurements revealed that adsorbed COE-3 and its Fab and Fc fragments retained their globular structure, forming layers that did not penetrate substantially into the oil phase. COE-3 and Fc were found to adsorb flat-on to the interface, with denser 45 and 42 Å inner layers, respectively, in contact with the oil and a more diffuse 17-21 Å outer layer caused by fragments adsorbing in a tilted manner. In contrast, Fab fragments formed a uniform 60 Å monolayer. Monolayers were formed under all conditions studied (10-200 ppm, using three isotopic contrasts), although changes in packing density across the COE-3 and Fc layers were observed. COE-3 had a higher affinity to the interface than either of its constituent fragments, while Fab had a lower interfacial affinity consistent with its higher net surface charge. This study extends the application of high-resolution neutron reflection measurements to the study of protein adsorption at the oil/water interface using an experimental setup mimicking the protein drug product in a siliconized prefilled syringe.

How New Support Devices Change Critical Care Delivery.

Mechanical support devices are used to support failing cardiac, respiratory, or both systems. Since Gibbon developed the cardiopulmonary bypass in 1953, collaborative efforts by medical centers, bioengineers, industry, and the National Institutes of Health have led to development of mechanical devices to support heart, lung, or both. These devices are used as a temporary or long-term measures for acute collapse of circulatory system and/or respiratory failure. Patients are managed on these support devices as a bridge to recovery, bridge to long term devices, or bridge to transplant. The progress in development of these devices has improved mortality and quality of life in select groups of patients. Care of these patients requires a multidisciplinary team approach, which includes cardiac surgeons, critical care physicians, cardiologists, pulmonologists, nursing staff, and perfusionists. Using a team approach improves outcomes in these patients.

The Role and Impact of Extracorporeal Membrane Oxygenation in Critical Care.

Use of extracorporeal membrane oxygenation (ECMO) has been exponentially increasing over the last decade and is now considered a mainstream lifesaving treatment modality in critical care medicine. However, the need for physician education, training, and experience remains imperative. Although ECMO has traditionally been used in end-stage lung disease and circulatory collapse, it is being adopted for use in right heart failure, as a bridge to heart and lung transplantation, and as rescue therapy for both sepsis and post-organ transplantation. The following article discusses indications, management, complications, and challenges of ECMO as well as our experience at the Houston Methodist DeBakey Heart & Vascular Center.

Developing and testing a comprehensive tool to assess family meetings: Empirical distinctions between high- and low-quality meetings.

BACKGROUND: The heterogeneity with regard to findings on family meetings (or conferences) suggests a need to better understand factors that influence family meetings. While earlier studies have explored frequency or timing of family meetings, little is known about how factors (such as what is said during meetings, how it is said, and by whom) influence family meeting quality. OBJECTIVES: (1) To develop an evaluation tool to assess family meetings (Phase 1); (2) to identify factors that influence meeting quality by evaluating 34 family meetings (Phase 2). MATERIALS AND METHODS: For Phase 1, methods included developing a framework, cognitive testing, and finalizing the evaluation tool. The tool consisted of Facilitator Characteristics (i.e., gender, experience, and specialty of the person leading the meeting), and 22 items across 6 Meeting Elements (i.e., Introductions, Information Exchanges, Decisions, Closings, Communication Styles, and Emotional Support) and sub-elements. For Phase 2, methods included training evaluators, assessing family meetings, and analyzing data. We used Spearman's rank-order correlations to calculate meeting quality. Qualitative techniques were used to analyze free-text. RESULTS: No Facilitator Characteristic had a significant correlation with meeting quality. Sub-elements related to communication style and emotional support most strongly correlated with high-quality family meetings, as well as whether "next steps" were outlined (89.66%) and whether "family understanding" was elicited (86.21%). We also found a significant and strong positive association between overall proportion scores and evaluators' ratings (rs=0.731, p<0.001). CONCLUSIONS: We filled a gap by developing an evaluation tool to assess family meetings, and we identified how what is said during meetings impacts quality.

Beta-catenin is a mediator of the response of fibroblasts to irradiation.

Radiation causes soft tissue complications that include fibrosis and deficient wound healing. beta-Catenin, a key component in the canonical Wnt-signaling pathway, is activated in fibrotic processes and wound repair and, as such, could play a role in mediating cellular responses to irradiation. beta-Catenin can form a transcriptionally active complex with members of the Tcf family. A reporter mouse model, in addition to human cell cultures, was used to demonstrate that ionizing radiation activates beta-catenin-mediated, Tcf-dependent transcription both in vitro and in vivo. Furthermore, radiation activates beta-catenin via a Wnt-mediated mechanism, as in the presence of dickkopf-1, an inhibitor of Wnt receptor activation, beta-catenin levels did not increase after irradiation. Fibroblast cell cultures were derived from mice expressing either null or stabilized beta-catenin alleles. Cells expressing stabilized beta-catenin alleles had a higher proliferation rate and formed more colony-forming units than wild-type or null cells after irradiation. Wound healing was studied in these same mice after irradiation. There was a positive correlation between the tensile strength of the wound, the expression levels of type 1 collagen in the skin, and beta-catenin levels. Mice treated with lithium showed increased beta-catenin levels and increased wound strength. beta-Catenin mediates the effects of ionizing radiation in fibroblasts, and its modulation has the potential to decrease the severity of radiation-induced soft tissue complications.