Bovine Placentome-Derived Extracellular Matrix: A Sustainable 3D Scaffold for Cultivated Meat.

Cultivated meat, an advancement in cellular agriculture, holds promise in addressing environmental, ethical, and health challenges associated with traditional meat production. Utilizing tissue engineering principles, cultivated meat production employs biomaterials and technologies to create cell-based structures by introducing cells into a biocompatible scaffold, mimicking tissue organization. Among the cell sources used for producing muscle-like tissue for cultivated meats, primary adult stem cells like muscle satellite cells exhibit robust capabilities for proliferation and differentiation into myocytes, presenting a promising avenue for cultivated meat production. Evolutionarily optimized for growth in a 3D microenvironment, these cells benefit from the biochemical and biophysical cues provided by the extracellular matrix (ECM), regulating cell organization, interactions, and behavior. While plant protein-based scaffolds have been explored for their utilization for cultivated meat, they lack the biological cues for animal cells unless functionalized. Conversely, a decellularized bovine placental tissue ECM, processed from discarded birth tissue, achieves the biological functionalities of animal tissue ECM without harming animals. In this study, collagen and total ECM were prepared from decellularized bovine placental tissues. The collagen content was determined to be approximately 70% and 40% in isolated collagen and ECM, respectively. The resulting porous scaffolds, crosslinked through a dehydrothermal (DHT) crosslinking method without chemical crosslinking agents, supported the growth of bovine myoblasts. ECM scaffolds exhibited superior compatibility and stability compared to collagen scaffolds. In an attempt to make cultivate meat constructs, bovine myoblasts were cultured in steak-shaped ECM scaffolds for about 50 days. The resulting construct not only resembled muscle tissues but also displayed high cellularity with indications of myogenic differentiation. Furthermore, the meat constructs were cookable and able to sustain the grilling/frying. Our study is the first to utilize a unique bovine placentome-derived ECM scaffold to create a muscle tissue-like meat construct, demonstrating a promising and sustainable option for cultivated meat production.

Optimized Adipogenic Differentiation and Delivery of Bovine Umbilical Cord Stem Cells for Cultivated Meat.

Cultivated meat, also known as cell-based or clean meat, utilizes mesenchymal stem cells to cultivate mature cell types like adipocytes, which are pivotal for imparting the desired taste and texture. The delivery of differentiated cells, crucial in cultivated meat production, is facilitated through extensive exploration of 3D culturing techniques mimicking physiological environments. In this study, we investigated the adipogenic differentiation potential of bovine umbilical cord stem cells (BUSCs), sourced from discarded birth tissue, and assessed the feasibility of delivering differentiated cells for cultivated meat using gelatin methacrylate (GelMA) as a carrier for adipose tissue. Various adipogenic inducers, previously reported to be effective for human mesenchymal stem cells (hMSCs), were evaluated individually or in combination for their efficacy in promoting the adipogenesis of BUSCs. Surprisingly, while the traditional adipogenic inducers, including insulin, dexamethasone, isobutylmethylxantine (IBMX), indomethacin, and rosiglitazone, showed no significant effect on the adipogenic differentiation of BUSCs, efficient differentiation was achieved in the presence of a fatty acid cocktail. Furthermore, we explored methods for the delivery of BUSCs. Differentiated cells were delivered either encapsulated in GelMA hydrogel or populated on the surface of GelMA microparticles (MPs) as the adipose component of cultivated meat. Our findings reveal that after adipogenic induction, the lipid production per cell was comparable when cultured either within hydrogel or on MPs. However, GelMA-MPs supported better cell growth compared to hydrogel encapsulation. Consequently, the overall lipid production is higher when BUSCs are delivered via GelMA-MPs rather than encapsulation. This study not only systematically evaluated the impact of common adipogenic inducers on BUSCs, but also identified GelMA-MPs as a promising carrier for delivering bovine adipocytes for cultivated meat production.

Two Weeks Versus One Week of Maximal Patient-Intensivist Continuity for Adult Medical Intensive Care Patients: A Two-Center Target Trial Emulation.

OBJECTIVES: To compare outcomes for 2 weeks vs. 1 week of maximal patient-intensivist continuity in the ICU. DESIGN: Retrospective cohort study. SETTING: Two U.S. urban, teaching, medical ICUs where intensivists were scheduled for 2-week service blocks: site A was in the Midwest and site B was in the Northeast. PATIENTS: Patients 18 years old or older admitted to a study ICU between March 1, 2017, and February 28, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We applied target trial emulation to compare admission during an intensivist's first week (as a proxy for 2 wk of maximal continuity) vs. admission during their second week (as a proxy for 1 wk of maximal continuity). Outcomes included hospital mortality, ICU length of stay, and, for mechanically ventilated patients, duration of ventilation. Exploratory outcomes included imaging, echocardiogram, and consultation orders. We used inverse probability weighting to adjust for baseline differences and random-effects meta-analysis to calculate overall effect estimates. Among 2571 patients, 1254 were admitted during an intensivist's first week and 1317 were admitted during a second week. At sites A and B, hospital mortality rates were 25.8% and 24.2%, median ICU length of stay were 4 and 2 days, and median mechanical ventilation durations were 3 and 3 days, respectively. There were no differences in adjusted mortality (odds ratio [OR], 1.01 [95% CI, 0.96-1.06]) or ICU length of stay (-0.25 d [-0.82 d to +0.32 d]) for 2 weeks vs. 1 week of maximal continuity. Among mechanically ventilated patients, there were no differences in adjusted mortality (OR, 1.00 [0.87-1.16]), ICU length of stay (+0.06 d [-0.78 d to +0.91 d]), or duration of mechanical ventilation (+0.37 d [-0.46 d to +1.21 d]) for 2 weeks vs. 1 week of maximal continuity. CONCLUSIONS: Two weeks of maximal patient-intensivist continuity was not associated with differences in clinical outcomes compared with 1 week in two medical ICUs.

Human Mesenchymal Stem Cells on Size-Sorted Gelatin Hydrogel Microparticles Show Enhanced In Vitro Wound Healing Activities.

The demand for innovative therapeutic interventions to expedite wound healing, particularly in vulnerable populations such as aging and diabetic patients, has prompted the exploration of novel strategies. Mesenchymal stem cell (MSC)-based therapy emerges as a promising avenue for treating acute and chronic wounds. However, its clinical application faces persistent challenges, notably the low survivability and limited retention time of engraftment in wound environments. Addressing this, a strategy to sustain the viability and functionality of human MSCs (hMSCs) in a graft-able format has been identified as crucial for advanced wound care. Hydrogel microparticles (HMPs) emerge as promising entities in the field of wound healing, showcasing versatile capabilities in delivering both cells and bioactive molecules/drugs. In this study, gelatin HMPs (GelMPs) were synthesized via an optimized mild processing method. GelMPs with distinct diameter sizes were sorted and characterized. The growth of hMSCs on GelMPs with various sizes was evaluated. The release of wound healing promoting factors from hMSCs cultured on different GelMPs were assessed using scratch wound assays and gene expression analysis. GelMPs with a size smaller than 100 microns supported better cell growth and cell migration compared to larger sizes (100 microns or 200 microns). While encapsulation of hMSCs in hydrogels has been a common route for delivering viable hMSCs, we hypothesized that hMSCs cultured on GelMPs are more robust than those encapsulated in hydrogels. To test this hypothesis, hMSCs were cultured on GelMPs or in the cross-linked methacrylated gelatin hydrogel (GelMA). Comparative analysis of growth and wound healing effects revealed that hMSCs cultured on GelMPs exhibited higher viability and released more wound healing activities in vitro. This observation highlights the potential of GelMPs, especially those with a size smaller than 100 microns, as a promising carrier for delivering hMSCs in wound healing applications, providing valuable insights for the optimization of advanced therapeutic strategies.

Self-reported Patient-perpetrated Sexual Harassment and Subsequent Reporting Among Health Care Clinicians in Urology and Obstetrics-Gynecology: A Cohort Survey.

OBJECTIVE: To understand the experiences of urologists and obstetricians-gynecologists (obgyns) with patient-perpetrated sexual harassment (PPSH) since the clinical focus of these specialists may make them particularly vulnerable to PPSH. METHODS: A multiple-choice anonymous online survey was administered in the Departments of Urology and Obgyn at a single institution from 22 September, 2022-18 October, 2022. The survey assessed if clinicians had experienced PPSH, including gender harassment, unwanted sexual attention, and/or sexual coercion from patients, where PPSH was witnessed or experienced, and whether implementation of chaperones impacted their experiences with PPSH. We conducted descriptive analysis by clinician sex, department, and form of PPSH experienced. We also performed logistic regression analysis to identify clinician factors associated with experiencing PPSH. RESULTS: Majority of respondents reported that they experienced or witnessed PPSH (78%, N = 100). Gender harassment was the most common form of PPSH experienced by clinicians (53%, N = 68). PPSH was most often experienced or witnessed in clinic (74%, N = 70) and inpatient wards (66%, N = 62). Of those who utilized chaperones, 80% (N = 57) of clinicians reported they either did not reduce or were unsure if they reduced PPSH. When adjusting for clinician factors, being a female clinician (adjusted odd ratio [aOR] = 5.1, 95% confidence interval (CI) 1.5-17.3), trainee (aOR = 6.9, 95% CI 1.1-44.6), or a urologist (aOR = 18.1, 95% CI 2.0-166.1) were associated with experiencing PPSH. CONCLUSION: Our study highlights the pervasiveness of PPSH among urologists and obgyns. Future studies should elucidate what policy changes can be effective in protecting clinicians from PPSH.

Stepping On Fall Prevention Program Reduces Falls in Older Adults: An Observational Prospective Study.

The purpose of the current study was to assess the impact of the Stepping On fall prevention program on the incidence of falls and frailty measures in older adults. Participants completed pre- and post-fall prevention program questionnaires and the Frail Scale Assessment at baseline and post-program. They also completed a follow-up questionnaire and Frail Scale Assessment at 6- and 12-month intervals post-program. Univariate analysis was performed comparing robust (n = 11), pre-frail (n = 29), and frail (n = 7) participants. Frail participants were significantly older (mean age = 77.7 years [SD = 4.9 years] vs. 74 years [SD = 5.9 years] vs. 70.4 [SD = 3.9], respectively; p = 0.026) and more likely to live alone (71.4% vs. 65.5% vs. 18.2%, respectively; p = 0.017) compared to pre-frail and robust participants. At 12-month post-program, reported falls and frailty scores decreased compared to baseline (12.8% vs. 29.8%, p = 0.044 and 0.91 [SD = 1.1] vs. 1.3 [SD = 1.082], respectively; p = 0.009). Data show that 41.4% of pre-frail participants at baseline improved to robust. Participation in Stepping On led to a decrease in reported falls and frailty scores 12 months post-program, suggesting that participation in the program may help delay frailty progression. [Journal of Gerontological Nursing, 49(8), 43-50.].

The Use of a Fabricated Endotracheal Tube During an Acute Massive Pulmonary Hemorrhage: A Case Report.

A massive pulmonary hemorrhage is an emergency that can lead to airway compromise and cardiovascular collapse. The goals of airway management are to isolate and protect the nonbleeding lung while providing a route for interventions to diagnose and control the bleeding site. We present a case of an adult male with a lung mass who underwent a bronchoscopy and cryobiopsy that was complicated by a massive pulmonary hemorrhage. We report the successful use of an elongated fabricated end-to-end endotracheal tube to manage his airway during this time-critical situation.

Patient and clinician perspectives of a remote monitoring program for COVID-19 and lessons for future programs.

COVID Watch is a remote patient monitoring program implemented during the pandemic to support home dwelling patients with COVID-19. The program conferred a large survival advantage. We conducted semi-structured interviews of 85 patients and clinicians using COVID Watch to understand how to design such programs even better. Patients and clinicians found COVID Watch to be comforting and beneficial, but both groups desired more clarity about the purpose and timing of enrollment and alternatives to text-messages to adapt to patients' preferences as these may have limited engagement and enrollment among marginalized patient populations. Because inclusiveness and equity are important elements of programmatic success, future programs will need flexible and multi-channel human-to-human communication pathways for complex clinical interactions or for patients who do not desire tech-first approaches.

Bovine Fibroblast-Derived Extracellular Matrix Promotes the Growth and Preserves the Stemness of Bovine Stromal Cells during In Vitro Expansion.

Cultivated meat is a fast-growing research field and an industry with great potential to overcome the limitations of traditional meat production. Cultivated meat utilizes cell culture and tissue engineering technologies to culture a vast number of cells in vitro and grow/assemble them into structures mimicking the muscle tissues of livestock animals. Stem cells with self-renewal and lineage-specific differentiation abilities have been considered one of the key cell sources for cultivated meats. However, the extensive in vitro culturing/expansion of stem cells results in a reduction in their abilities to proliferate and differentiate. Extracellular matrix (ECM) has been used as a culturing substrate to support cell expansion for cell-based therapies in regenerative medicine due to its resemblance to the native microenvironment of cells. In this study, the effect of the ECM on the expansion of bovine umbilical cord stromal cells (BUSC) in vitro was evaluated and characterized. BUSCs with multi-lineage differentiation potentials were isolated from bovine placental tissue. Decellularized ECM prepared from a confluent monolayer of bovine fibroblasts (BF) is free of cellular components but contains major ECM proteins such as fibronectin and type I collagen and ECM-associated growth factors. Expansion of BUSC on ECM for three passages (around three weeks) resulted in about 500-fold amplification, while cells were amplified less than 10-fold when cultured on standard tissue culture plates (TCP). Moreover, the presence of ECM reduced the requirement for serum in the culture medium. Importantly, the cells amplified on ECM retained their differentiation abilities better than cells cultured on TCP. The results of our study support the notion that monolayer cell-derived ECM may be a strategy to expand bovine cells in vitro effectively and efficiently.

Adaptations within Palliative Care Delivery Models Due to the COVID-19 Pandemic at a Tertiary Care Hospital.

Background: Since the onset of the COVID-19 pandemic, all facets of palliative care provision for patients with serious illness have faced unparalleled challenges. Methods: We describe our palliative care program's response to the increased clinical volume associated with the pandemic by adapting workflows for inpatient and outpatient palliative care teams caring for oncology and nononcology populations. Results: During the initial surge, the demand for palliative care consultation for patients affected by SARS-CoV-2 was high, accounting for 75% of all inpatient palliative care referral requests for oncology and nononcology patients. Furthermore, our ambulatory clinic experienced a 40% increase in visits for complex oncology patients between February and December of 2020. Discussion: This article highlights transformations in palliative care delivery implemented in response to the pandemic and reflects on how these transformations have shaped our current care delivery models. We further delineate our intentional reliance on key population health principles to drive ongoing innovation in palliative care provision across our clinical teams.

Self-reported Sexual Harassment and Subsequent Reporting Among Internal Medicine Residency Trainees in the US.

This study uses survey data to describe the types of sexual harassment experienced by internal medicine residents, their knowledge of reporting mechanisms, their reporting intentions and actions, and satisfaction with reporting outcomes.

Patient and clinician perspectives of a remote monitoring program for COVID-19 and lessons for future programs.

COVID Watch is a remote patient monitoring program implemented during the pandemic to support home dwelling patients with COVID-19. The program conferred a large survival advantage. We conducted semi-structured interviews of 85 patients and clinicians using COVID Watch to understand how to design such programs even better. Patients and clinicians found COVID Watch to be comforting and beneficial, but both groups desired more clarity about the purpose and timing of enrollment and alternatives to text-messages to adapt to patients’ preferences as these may have limited engagement and enrollment among marginalized patient populations. Because inclusiveness and equity are important elements of programmatic success, future programs will need flexible and multi-channel human-to-human communication pathways for complex clinical interactions or patients who do not desire tech-first approaches.

A Tai Chi for Arthritis and Fall Prevention Program for Older Adults During COVID-19.

ABSTRACT: To minimize COVID-19 transmission, the University of Iowa suspended all in-person fall injury prevention programs in March 2020. However, falls continued to be the leading cause of injury-related mortality in Iowa; therefore, the university converted its in-person Tai Chi for Arthritis and Fall Prevention (TCAFP) program to a virtual program. Here, the authors describe the virtual TCAFP program and participants' overall experience. Among 83 older adults who participated in the first three virtual programs, 61 (73.5%) completed the programs. Of the 31 (37.3%) participants who filled out the postprogram satisfaction surveys, 30 (96.8%) found the Zoom platform easy to use and said the program met their expectations, 28 (90.3%) were happy with the quality of the instruction, and 29 (93.5%) said they learned the tai chi forms taught during the program and used an online video to practice between classes. Judging by the largely positive participant feedback, the authors considered the implementation of a virtual TCAFP program a success. The potential for the use of such a program beyond the pandemic to improve injury prevention efforts in rural environments warrants further exploration.

Are Opioid Infusions Used Inappropriately at End of Life? Results From a Quality/Safety Project.

CONTEXT: Opioid continuous infusions are commonly used for end-of-life (EOL) symptoms in hospital settings. However, prescribing practices vary, and even the recent literature contains conflicting protocols and guidelines for best practice. OBJECTIVES: To determine the prevalence of potentially inappropriate opioid infusion use for EOL comfort care at an academic medical center, and determine if inappropriate use is associated with distress. METHODS: Through literature review and iterative interdisciplinary discussion, we defined three criteria for "potentially inappropriate" infusion use. We conducted a retrospective, observational study of inpatients who died over six months, abstracting demographics, opioid use patterns, survival time, palliative care (PC) involvement, and evidence of patient/caregiver/staff distress from the electronic medical record. RESULTS: We identified 193 decedents who received opioid infusions for EOL comfort care. Forty-four percent received opioid infusions that were classified as "potentially inappropriate." Insufficient use of as-needed intravenous opioid boluses and use of opioid infusions in opioid-naïve patients were the most common problems observed. Potentially inappropriate infusions were associated with more frequent patient (24% vs. 2%; P < 0.001) and staff distress (10% vs. 2%; P = 0.02) and were less common when PC provided medication recommendations (20% vs. 50%; P < 0.001). CONCLUSION: Potentially inappropriate opioid infusions are prevalent at our hospital, an academic medical center with an active PC team and existing contracts for in-hospital hospice care. Furthermore, potentially inappropriate opioid infusions are associated with increased patient and staff distress. We are developing an interdisciplinary intervention to address this safety issue.

An accelerated hospital observation pathway to reduce length of stay for patients with COVID-19.

OBJECTIVES: Strategies to maintain hospital capacity during the COVID-19 pandemic included reducing hospital length of stay (LOS) for infected patients. We sought to evaluate the association between LOS and enrollment in the COVID Accelerated Care Pathway, which consisted of a hospital observation protocol and postdischarge automated text message-based monitoring. STUDY DESIGN: Retrospective matched cohort study of patients hospitalized from December 14, 2020, to January 31, 2021. METHODS: Participants were patients who presented to the emergency department with acute infection due to COVID-19, required hospitalization, and met pathway inclusion criteria. Participants were compared with a propensity score-matched cohort of patients with COVID-19 admitted to the same hospital during the 7 weeks preceding and following pathway implementation. RESULTS: There were 44 patients in the intervention group and 83 patients in the propensity score-matched cohort. The mean (SD) hospital LOS for patients in the intervention group was 1.7 (2.6) days compared with 3.9 (2.3) days for patients in the matched cohort (difference, -2.2 days; 95% CI, -3.3 to -1.1). In the intervention group, 2 patients (5%; 95% CI, 0%-15%) were rehospitalized within 14 days compared with 8 (10%; 95% CI, 4%-17%) in the matched cohort. CONCLUSIONS: Patients with COVID-19 who were managed through an accelerated hospital observation protocol and postdischarge monitoring service had reduced hospital LOS compared with patients receiving standard care. Hospital preparedness for future public health emergencies may involve the design of pathways that reduce the time that patients spend in the hospital, lower cost, and ensure continued recovery upon discharge.

A Brief Educational Intervention to Increase ED Initiation of Buprenorphine for Opioid Use Disorder (OUD).

BACKGROUND: Despite the evidence in support of the use of buprenorphine in the treatment of OUD and increasing ability of emergency medicine (EM) clinicians to prescribe it, emergency department (ED)-initiated buprenorphine is uncommon. Many EM clinicians lack training on how to manage acute opioid withdrawal or initiate treatment with buprenorphine. We developed a brief buprenorphine training program and assessed the impact of the training on subsequent buprenorphine initiation and knowledge retention. METHODS: We conducted a pilot randomized control trial enrolling EM clinicians to receive either a 30-min didactic intervention about buprenorphine (standard arm) or the didactic plus weekly messaging and a monetary inducement to administer and report buprenorphine use (enhanced arm). All participants were incentivized to complete baseline, immediate post-didactic, and 90-day knowledge and attitude assessment surveys. Our objective was to achieve first time ED buprenorphine prescribing events in clinicians who had not previously prescribed buprenorphine in the ED and to improve EM-clinician knowledge and perceptions about ED-initiated buprenorphine. We also assessed whether the incentives and reminder messaging in the enhanced arm led to more clinicians administering buprenorphine than those in the standard arm following the training; we measured changes in knowledge of and attitudes toward ED-initiated buprenorphine. RESULTS: Of 104 EM clinicians enrolled, 51 were randomized to the standard arm and 53 to the enhanced arm. Clinical knowledge about buprenorphine improved for all clinicians immediately after the didactic intervention (difference 19.4%, 95% CI 14.4% to 24.5%). In the 90 days following the intervention, one-third (33%) of all participants reported administering buprenorphine for the first time. Clinicians administered buprenorphine more frequently in the enhanced arm compared to the standard arm (40% vs. 26.3%, p = 0.319), but the difference was not statistically significant. The post-session knowledge improvement was not sustained at 90 days in the enhanced (difference 9.6%, 95% CI - 0.37% to 19.5%) or in the standard arm (difference 3.7%, 95% CI - 5.8% to 13.2%). All the participants reported an increased ability to recognize patients with opioid withdrawal at 90 days (enhanced arm difference .55, 95% CI .01-1.09, standard arm difference .85 95% CI .34-1.37). CONCLUSIONS: A brief educational intervention targeting EM clinicians can be utilized to achieve first-time prescribing and improve knowledge around buprenorphine and opioid withdrawal. The use of weekly messaging and gain-framed incentivization conferred no additional benefit to the educational intervention alone. In order to further expand evidence-based ED treatment of OUD, focused initiatives that improve clinician competence with buprenorphine should be explored. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03821103.

Comparative Effectiveness of an Automated Text Messaging Service for Monitoring COVID-19 at Home.

BACKGROUND: Although most patients with SARS-CoV-2 infection can be safely managed at home, the need for hospitalization can arise suddenly. OBJECTIVE: To determine whether enrollment in an automated remote monitoring service for community-dwelling adults with COVID-19 at home ("COVID Watch") was associated with improved mortality. DESIGN: Retrospective cohort analysis. SETTING: Mid-Atlantic academic health system in the United States. PARTICIPANTS: Outpatients who tested positive for SARS-CoV-2 between 23 March and 30 November 2020. INTERVENTION: The COVID Watch service consists of twice-daily, automated text message check-ins with an option to report worsening symptoms at any time. All escalations were managed 24 hours a day, 7 days a week by dedicated telemedicine clinicians. MEASUREMENTS: Thirty- and 60-day outcomes of patients enrolled in COVID Watch were compared with those of patients who were eligible to enroll but received usual care. The primary outcome was death at 30 days. Secondary outcomes included emergency department (ED) visits and hospitalizations. Treatment effects were estimated with propensity score-weighted risk adjustment models. RESULTS: A total of 3488 patients enrolled in COVID Watch and 4377 usual care control participants were compared with propensity score weighted models. At 30 days, COVID Watch patients had an odds ratio for death of 0.32 (95% CI, 0.12 to 0.72), with 1.8 fewer deaths per 1000 patients (CI, 0.5 to 3.1) (P = 0.005); at 60 days, the difference was 2.5 fewer deaths per 1000 patients (CI, 0.9 to 4.0) (P = 0.002). Patients in COVID Watch had more telemedicine encounters, ED visits, and hospitalizations and presented to the ED sooner (mean, 1.9 days sooner [CI, 0.9 to 2.9 days]; all P < 0.001). LIMITATION: Observational study with the potential for unobserved confounding. CONCLUSION: Enrollment of outpatients with COVID-19 in an automated remote monitoring service was associated with reduced mortality, potentially explained by more frequent telemedicine encounters and more frequent and earlier presentation to the ED. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute.