Checklists and consistency of care after resuscitation from in-hospital cardiac arrest: A pilot study.

BACKGROUND: In-hospital cardiac arrest (IHCA) with the return of spontaneous circulation (ROSC) is a clinical scenario associated with potentially devastating outcomes. OBJECTIVE: Inconsistencies in post-ROSC care exist and we sought to find a low cost way to decrease this variability. DESIGNS, SETTINGS, AND PARTICIPANTS: We obtained pre and post intervention metrics including percentage of IHCA with a timely electrocardiogram (ECG), arterial blood gas (ABG), physician documentation, and documentation of patient surrogate communication after ROSC. INTERVENTION: We developed and implemented a post-ROSC checklist for IHCA and measured post-ROSC clinical care delivery metrics at our hospital during a 1-year pilot period. MAIN OUTCOME AND RESULTS: After the introduction of the checklist, 83.7% of IHCA had an ECG within 1 h of ROSC, compared to a baseline of 62.8% (p = 0.01). The rate of physician documentation within 6 h of ROSC was 74.4% after introduction of the checklist, compared to a baseline of 49.5% (p < 0.01). The percentage of IHCA with ROSC that completed all four of the critical post-ROSC tasks after the introduction of the post-ROSC checklist was 51.1% as compared to 19.4% before implementation (p < 0.01). CONCLUSIONS: Our study demonstrated improved consistency in completing post-ROSC clinical tasks after the introduction of a post-ROSC checklist to our hospital. This work suggests that the implementation of a checklist can have meaningful impacts on task completion in the post-ROSC setting. Despite this, considerable inconsistencies in post-ROSC care persisted after the intervention indicating the limits of checklists in this setting. Future work is needed to identify interventions that can further improve post-ROSC processes of care.

Utilizing preoperative arterial embolization to minimize blood loss at time of vulvar sarcoma resection: A case report.

Selective arterial embolization has long been utilized in the field of obstetrics and gynecology as both a prophylactic and therapeutic measure. We present a case of a highly vascularized, poorly differentiated, radiation-related vulvar sarcoma that was resected immediately following selective arterial embolization. Arterial embolization in patients with gynecologic malignancies has been shown to compromise blood supply to the tumor and decrease the risk of hemorrhage and related surgical complications. In this case, the use of embolization prior to surgery appeared to result in a less morbid procedure for the patient with decreased blood loss and improved quality of life thereafter. Based on the presented case, we believe that arterial embolization can be considered a safe preoperative intervention to decrease surgical risk, particularly hemorrhage, at time of resection of highly vascularized vulvar tumors.

Determining consistency of care after resuscitation from in-hospital cardiac arrest, a retrospective analysis at a tertiary care academic medical center.

BACKGROUND: Few guidelines have focused on the care delivered after return of spontaneous circulation (ROSC). Post ROSC best practice guidelines lack clarity about important tasks to accomplish in the first hours after ROSC. OBJECTIVES AND METHODS: We conducted a retrospective cohort analysis of adults who had suffered an in hospital cardiac arrest (IHCA) with ROSC over a two-year period to determine the completion rate of critical tasks in the immediate post-ROSC period: ECG within one hour, ABG within one hour, physician documentation within six hours, and surrogate communication within six hours. RESULTS: In the 113 reviewed cases, there was significant variance between completion of all four (19.4%), three (35.3%), two (32.7%), one (20.6%) and none (1.7%) of these critical post ROSC tasks. We observed that 62.8% of IHCA with ROSC had an ECG obtained within one hour of ROSC. The rate of obtaining an ABG within one hour of ROSC was 76.9%. 49.5% of cases had physician documentation of the resuscitation within six hours of ROSC. The rate of documenting surrogate communication within six hours of ROSC was 69.9%. CONCLUSIONS: Our study demonstrated that the completion rates of critical tasks in the post ROSC setting were suboptimal within our patient cohort. This provides a baseline for the development of future best practice guidelines and clinical decision-making aids for post ROSC care after IHCA. This can lead to future research in coupling specific care tasks to post ROSC patient outcomes.

Astrocytic laminin-211 drives disseminated breast tumor cell dormancy in brain.

Although dormancy is thought to play a key role in the metastasis of breast tumor cells to the brain, our knowledge of the molecular mechanisms regulating disseminated tumor cell (DTC) dormancy in this organ is limited. Here using serial intravital imaging of dormant and metastatic triple-negative breast cancer lines, we identify escape from the single-cell or micrometastatic state as the rate-limiting step towards brain metastasis. We show that every DTC occupies a vascular niche, with quiescent DTCs residing on astrocyte endfeet. At these sites, astrocyte-deposited laminin-211 drives DTC quiescence by inducing the dystroglycan receptor to associate with yes-associated protein, thereby sequestering it from the nucleus and preventing its prometastatic functions. These findings identify a brain-specific mechanism of DTC dormancy and highlight the need for a more thorough understanding of tumor dormancy to develop therapeutic approaches that prevent brain metastasis.

Higher severe acute respiratory syndrome coronavirus 2 infection rate in pregnant patients.

BACKGROUND: During the early months of the coronavirus disease 2019 pandemic, risks associated with severe acute respiratory syndrome coronavirus 2 in pregnancy were uncertain. Pregnant patients can serve as a model for the success of clinical and public health responses during public health emergencies as they are typically in frequent contact with the medical system. Population-based estimates of severe acute respiratory syndrome coronavirus 2 infections in pregnancy are unknown because of incomplete ascertainment of pregnancy status or inclusion of only single centers or hospitalized cases. Whether pregnant women were protected by the public health response or through their interactions with obstetrical providers in the early months of pandemic is not clearly understood. OBJECTIVE: This study aimed to estimate the severe acute respiratory syndrome coronavirus 2 infection rate in pregnancy and to examine the disparities by race and ethnicity and English language proficiency in Washington State. STUDY DESIGN: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection diagnosed between March 1, 2020, and June 30, 2020 were identified within 35 hospitals and clinics, capturing 61% of annual deliveries in Washington State. Infection rates in pregnancy were estimated overall and by Washington State Accountable Community of Health region and cross-sectionally compared with severe acute respiratory syndrome coronavirus 2 infection rates in similarly aged adults in Washington State. Race and ethnicity and language used for medical care of pregnant patients were compared with recent data from Washington State. RESULTS: A total of 240 pregnant patients with severe acute respiratory syndrome coronavirus 2 infections were identified during the study period with 70.7% from minority racial and ethnic groups. The principal findings in our study were as follows: (1) the severe acute respiratory syndrome coronavirus 2 infection rate was 13.9 per 1000 deliveries in pregnant patients (95% confidence interval, 8.3-23.2) compared with 7.3 per 1000 (95% confidence interval, 7.2-7.4) in adults aged 20 to 39 years in Washington State (rate ratio, 1.7; 95% confidence interval, 1.3-2.3); (2) the severe acute respiratory syndrome coronavirus 2 infection rate reduced to 11.3 per 1000 deliveries (95% confidence interval, 6.3-20.3) when excluding 45 cases of severe acute respiratory syndrome coronavirus disease 2 detected through asymptomatic screening (rate ratio, 1.3; 95% confidence interval, 0.96-1.9); (3) the proportion of pregnant patients in non-White racial and ethnic groups with severe acute respiratory syndrome coronavirus disease 2 infection was 2- to 4-fold higher than the race and ethnicity distribution of women in Washington State who delivered live births in 2018; and (4) the proportion of pregnant patients with severe acute respiratory syndrome coronavirus 2 infection receiving medical care in a non-English language was higher than estimates of pregnant patients receiving care with limited English proficiency in Washington State (30.4% vs 7.6%). CONCLUSION: The severe acute respiratory syndrome coronavirus 2 infection rate in pregnant people was 70% higher than similarly aged adults in Washington State, which could not be completely explained by universal screening at delivery. Pregnant patients from nearly all racial and ethnic minority groups and patients receiving medical care in a non-English language were overrepresented. Pregnant women were not protected from severe acute respiratory syndrome coronavirus 2 infection in the early months of the pandemic. Moreover, the greatest burden of infections occurred in nearly all racial and ethnic minority groups. These data coupled with a broader recognition that pregnancy is a risk factor for severe illness and maternal mortality strongly suggested that pregnant people should be broadly prioritized for coronavirus disease 2019 vaccine allocation in the United States similar to some states.

Disease severity, pregnancy outcomes, and maternal deaths among pregnant patients with severe acute respiratory syndrome coronavirus 2 infection in Washington State.

BACKGROUND: Evidence is accumulating that coronavirus disease 2019 increases the risk of hospitalization and mechanical ventilation in pregnant patients and for preterm delivery. However, the impact on maternal mortality and whether morbidity is differentially affected by disease severity at delivery and trimester of infection are unknown. OBJECTIVE: This study aimed to describe disease severity and outcomes of severe acute respiratory syndrome coronavirus 2 infections in pregnancy across the Washington State, including pregnancy complications and outcomes, hospitalization, and case fatality. STUDY DESIGN: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and June 30, 2020, were identified in a multicenter retrospective cohort study from 35 sites in Washington State. Sites captured 61% of annual state deliveries. Case-fatality rates in pregnancy were compared with coronavirus disease 2019 fatality rates in similarly aged adults in Washington State using rate ratios and rate differences. Maternal and neonatal outcomes were compared by trimester of infection and disease severity at the time of delivery. RESULTS: The principal study findings were as follows: (1) among 240 pregnant patients in Washington State with severe acute respiratory syndrome coronavirus 2 infections, 1 in 11 developed severe or critical disease, 1 in 10 were hospitalized for coronavirus disease 2019, and 1 in 80 died; (2) the coronavirus disease 2019-associated hospitalization rate was 3.5-fold higher than in similarly aged adults in Washington State (10.0% vs 2.8%; rate ratio, 3.5; 95% confidence interval, 2.3-5.3); (3) pregnant patients hospitalized for a respiratory concern were more likely to have a comorbidity or underlying conditions including asthma, hypertension, type 2 diabetes mellitus, autoimmune disease, and class III obesity; (4) 3 maternal deaths (1.3%) were attributed to coronavirus disease 2019 for a maternal mortality rate of 1250 of 100,000 pregnancies (95% confidence interval, 257-3653); (5) the coronavirus disease 2019 case fatality in pregnancy was a significant 13.6-fold (95% confidence interval, 2.7-43.6) higher in pregnant patients than in similarly aged individuals in Washington State with an absolute difference in mortality rate of 1.2% (95% confidence interval, -0.3 to 2.6); and (6) preterm birth was significantly higher among women with severe or critical coronavirus disease 2019 at delivery than for women who had recovered from coronavirus disease 2019 (45.4% severe or critical coronavirus disease 2019 vs 5.2% mild coronavirus disease 2019; P<.001). CONCLUSION: Coronavirus disease 2019 hospitalization and case-fatality rates in pregnant patients were significantly higher than in similarly aged adults in Washington State. These data indicate that pregnant patients are at risk of severe or critical disease and mortality compared to nonpregnant adults, and also at risk for preterm birth.

Hydrogel-fibre composites with independent control over cell adhesion to gel and fibres as an integral approach towards a biomimetic artificial ECM.

In the body, cells are surrounded by an interconnected mesh of insoluble, bioactive protein fibres to which they adhere in a well-controlled manner, embedded in a hydrogel-like highly hydrated matrix. True morphological and biochemical mimicry of this so-called extracellular matrix (ECM) remains a challenge but appears decisive for a successful design of biomimetic three-dimensional in vitro cell culture systems. Herein, an approach is presented which describes the fabrication and in vitro assessment of an artificial ECM which contains two major components, i.e. specifically biofunctionalized fibres and a semi-synthetic hyaluronic acid-based hydrogel, which allows control over cell adhesion towards both components. As proof of principle for the control of cell adhesion, RGD as well-known cell adhesive cue and the control sequence RGE are immobilized in the system. In vitro studies with primary human dermal fibroblasts were conducted to evaluate the specificity of cell adhesion and the potential of the composite system to support cell growth. Finally, one possible application example for guided cell growth is shown by the use of oriented fibres in a hydrogel matrix.

Microengineered PEG hydrogels: 3D scaffolds for guided cell growth.

Designing three-dimensional (3D) scaffolds for selective manipulation of cell growth is of high relevance for applications in regenerative medicine. Especially, scaffolds with oriented morphologies bear high potential to guide the restoration of specific tissues. The fabrication of hydrogel scaffolds that support long-term survival, proliferation, and unidirectional growth of embedded cells is presented here. Parallel channel structures are introduced into the bulk hydrogels by uniaxial freezing, providing stable, and uniform porosity suitable for cell invasion (pore diameters of 5-15 µm). In vitro assessment of the scaffolds with murine fibroblasts (NIH L929) shows a remarkable unidirectional movement along the channels, with the cells traveling several millimeters through the hydrogel.

Development and characterization of a coronary polylactic acid stent prototype generated by selective laser melting.

In-stent restenosis is still an important issue and stent thrombosis is an unresolved risk after coronary intervention. Biodegradable stents would provide initial scaffolding of the stenosed segment and disappear subsequently. The additive manufacturing technology Selective Laser Melting (SLM) enables rapid, parallel, and raw material saving generation of complex 3- dimensional structures with extensive geometric freedom and is currently in use in orthopedic or dental applications. Here, SLM process parameters were adapted for poly-L-lactid acid (PLLA) and PLLA-co-poly-ε-caprolactone (PCL) powders to generate degradable coronary stent prototypes. Biocompatibility of both polymers was evidenced by assessment of cell morphology and of metabolic and adhesive activity at direct and indirect contact with human coronary artery smooth muscle cells, umbilical vein endothelial cells, and endothelial progenitor cells. γ-sterilization was demonstrated to guarantee safety of SLM-processed parts. From PLLA and PCL, stent prototypes were successfully generated and post-processing by spray- and dip-coating proved to thoroughly smoothen stent surfaces. In conclusion, for the first time, biodegradable polymers and the SLM technique were combined for the manufacturing of customized biodegradable coronary artery stent prototypes. SLM is advocated for the development of biodegradable coronary PLLA and PCL stents, potentially optimized for future bifurcation applications.

Topography-induced cell adhesion to Acr-sP(EO-stat-PO) hydrogels: the role of protein adsorption.

Topographic surface patterning of intrinsically non-adhesive P(EO-stat-PO)-based hydrogels can lead to the adhesion and spreading of fibroblasts. Explanations for this unexpected behavior are discussed, particularly with regard to non-specific protein adsorption from the serum-supplemented culture medium. The presence of serum proteins is shown to be essential for adhesion. Adsorption of plasma and ECM proteins (Fibronectin (FN) and Vitronectin (VN)) to the hydrogels is possible. The effect of VN on initial cell adhesion is analyzed in detail. It appears that VN is the main serum component that is crucial for initial cell adhesion to PEG and that surface topography is essential for further, durable adhesion establishment, and spreading.

Combined influence of substrate stiffness and surface topography on the antiadhesive properties of Acr-sP(EO-stat-PO) hydrogels.

Biomaterials that prevent nonspecific protein adsorption and cell adhesion are of high relevance for diverse applications in tissue engineering and diagnostics. One of the most widely applied materials for this purpose is Poly(ethylene glycol) (PEG). We have investigated how micrometer line topography and substrate elasticity act upon the antiadhesive properties of PEG-based hydrogels. In our studies we apply bulk hydrogel cross-linked from star-shaped poly(ethylene oxide-stat-propylene oxide) macromonomers. Substrate surfaces were topographically patterned via replica molding. Additionally, the mechanical properties were altered by variations in the cross-linking density. Surface patterns with dimensions in the range of the cells' own size, namely 10 µm wide grooves, induced significant cell adhesion and spreading on the Acr-sP(EO-stat-PO) hydrogels. In contrast, there was only little adhesion to smaller and larger pattern sizes and no adhesion at all on the smooth substrates, regardless the rigidity of the gel. The effect of varied substrate stiffness on cell behavior was only manifest in combination with topography. Softer substrates with line patterns lead to significantly higher cell adhesion and spreading than stiff substrates. We conclude that the physical and mechanical surface characteristics can eliminate the nonadhesive properties of PEG-based hydrogels to a large extent. This has to be taken into account when designing surfaces for biomedical application such as scaffolds for tissue engineering which rely on the inertness of PEG.

A hydrophobic perfluoropolyether elastomer as a patternable biomaterial for cell culture and tissue engineering.

We present a systematic study of a perfluoropolyether (PFPE)-based elastomer as a new biomaterial. Besides its excellent long-term stability and inertness, PFPE can be decorated with topographical surface structures by replica molding. Micrometer-sized pillar structures led to considerably different cell morphology of fibroblasts. Although PFPE is a very hydrophobic material we could show that PFPE substrates allow cell adhesion and spreading of primary human fibroblasts (HDF) very similar to that observed on standard cell culture substrates. Less advanced cell spreading was observed for L929 (murine fibroblast cell line) cells during the first 5 h in culture which was accompanied by retarded recruitment of α(v)ß(3)-integrin into focal adhesions (FAs). After 24 h distinct FAs were evident also in L929 cells on PFPE. Furthermore, organization of soluble FN into a fibrillar ECM network was shown for hdF and L929 cells. Based on these results PFPE is believed to be a suitable substrate for several biological applications. On the one hand it is an ideal cell culture substrate for fundamental research of substrate-independent adhesion signaling due to its different characteristics (e.g. wettability, elasticity) compared to glass or TCPS. On the other hand it could be a promising implant material, especially due to its straightforward patternability, which is a tool to direct cell growth and differentiation.

Induction of specific macrophage subtypes by defined micro-patterned structures.

In this study, we investigated the influence of different perfluoropolyether (PFPE) microstructures on the inflammatory response of human macrophages. We generated four different microstructured PFPE surfaces by replica molding from silicon masters. The function-associated surface markers 27E10 and CD163 were monitored using flow cytometry to measure the pro- and anti-inflammatory reactions. Inflammatory mediator expression was measured at the protein and mRNA level. Lipopolysaccharide treatment served as positive control for pro-inflammatory activation. We observed that each micropattern induced a specific morphology, phenotype and mediator profile. A microstructure of regular grooves induced a pro-inflammatory phenotype (M1) which was not accompanied by release of pro-inflammatory mediators. However, the larger cylindrical posts induced an anti-inflammatory phenotype (M2) with a remarkable down-regulation of CXCL10. Smaller posts with a shorter distance exhibited a stronger pro-inflammatory response than those with a longer distance, on the levels of both phenotype and mediator release. Regression analysis suggests that the geometrical parameters of the microstructures, specifically the period of structures, may play an important role in macrophage response. Optimization of such microstructures may provide a method to invoke a predictable response of macrophages to implants and control the mediator release.

Surface topography induces fibroblast adhesion on intrinsically nonadhesive poly(ethylene glycol) substrates.

Important in developing new biomaterials is the prevention of unspecific protein adsorption and cell interactions that in vivo can lead to a foreign body reaction. On the other hand, the material should support the growth of a specific cell type in a defined way. We investigate the possibility of manipulating cellular behavior on an intrinsically nonadhesive material by topographic patterning without additional surface chemistry modifications. The biomaterial applied is a hydrogel cross-linked from star-shaped poly(ethylene glycol) macromonomers (starPEG). Cell biological studies with a mouse fibroblast cell line (L929) showed that, while substrates with a smooth surface are nonadhesive, as expected, imprinted topography enabled cell adhesion and spreading. The fibroblasts aligned to micrometer groove patterns and were, depending on the respective dimensions, able to span or enter the grooves. Especially substrates with topography dimensions in the cell size range or smaller (<10 microm) lead to an establishment of stable cell-surface contacts (vinculin and actin accumulation). On micrometer post patterns the cells spread on top of the pillars and wrapped around the structures. The strong influence of the topography shows that nonadhesive materials do not necessarily have to be specifically biofunctionalized to enable cell adhesion. Possible explanations for the peculiar cell behavior are discussed in terms of (initial) protein adsorption and geometry-dependent cytoskeletal arrangements.