The Minnesota Critical Care Working Group 1: Monitoring and Coordinating Statewide Critical Care Surge Response in the COVID-19 Pandemic, March 2020 Through July 1, 2021.

Background: In response to the COVID-19 pandemic and as part of the statewide health care coalition response, the Minnesota Critical Care Working Group (CCWG), composed of interprofessional leaders from the state's nine largest health systems, was established and entrusted to plan and coordinate critical care support for Minnesota from March 2020 through July 1, 2021.

Research Question: Can a statewide CCWG develop contingency and crisis-level surge strategies and indicators in response to the COVID-19 pandemic while evolving into a highly collaborative team?

Study Design And Methods: CCWG members (intensivists, ethicists, nurses, Minnesota Department of Health and Minnesota Hospital Association leaders) met by audio video conferencing as often as daily assessing COVID-19 and non-COVID-19 hospitalization data, developed surge indicators reflecting contingency vs crisis conditions, and planned responses collaboratively. A foundation of collaboration and teamwork developed which facilitated an effective statewide response.

The Minnesota Critical Care Working Group 2: Crisis Conditions During the COVID-19 Pandemic, July 2021 through March 2022.

Background: The Minnesota Statewide Healthcare Coordination Center requested that the Minnesota Critical Care Working Group (CCWG) and Ethics Working Group (EWG), comprising interprofessional leaders from Minnesota's 9 largest health systems, plan and coordinate critical care operations during the COVID-19 pandemic, including the fall 2021 surge.

Research Question: Can a statewide working group collaboratively analyze real-time evidence to identify crisis conditions and to engage state leadership to implement care processes?

Study Design And Methods: The CCWG and EWG met via videoconferencing during the severe surge of fall 2021 to analyze evidence and plan for potential crisis care conditions. Five sources of evidence informed their actions: group consensus on operating conditions, federal teletracking data, the Medical Operations Coordination Center (MOCC) patient placement data, and 2 surveys created and distributed to hospitals and health care professionals.

Impact of site-specific conjugation strategies on the pharmacokinetics of antibody conjugated radiotherapeutics.

Antibody radionuclide conjugates are an emerging modality for targeted imaging and potent therapy of disseminated disease. Coupling of radionuclides to monoclonal antibodies (mAbs) is typically achieved by applying non-site-specific labelling techniques. With the ambition of reducing variability, increasing labelling efficacy and stability, several site-specific conjugation strategies have been developed in recent years for toxin- and fluorophore-mAb conjugates.

Competency-Based Virtual Clinical Practicum in Response to COVID-19 Pandemic: A Quality Improvement Project.

Purpose: The purpose of the quality improvement (QI) project was to provide a learner and faculty preceptor high quality virtual clinical practicum (VCP) for Wound, Ostomy, Continence (WOC) Nurse learners during the COVID-19 pandemic and disseminate findings.

Participants And Setting: Project participants were registered nurses post-bachelor's degree or higher with a minimum of 1-year clinical experience who had completed and passed the didactic portion of a Wound Ostomy Continence Nursing Education Program (WOCNEP). Learners completing the WOCNEP's VCP and the faculty preceptors were the subjects for this QI report.

Photoactive immunoconjugates for targeted photodynamic therapy of cancer.

Photodynamic therapy (PDT) has been used as an alternative or as a complement of conventional approaches for cancer treatment. In PDT, the reactive oxygen species (ROS) produced from the interaction between the photosensitizer (PS), visible light and molecular oxygen, kill malignant cells by triggering a cascade of cytotoxic reactions. In this process, the PS plays an extremely important role in the effectiveness of the therapy.

Supraglottic airway devices are associated with asphyxial physiology after prolonged CPR in patients with refractory Out-of-Hospital cardiac arrest presenting for extracorporeal cardiopulmonary resuscitation.

Background: Multiple randomized clinical trials have compared specific airway management strategies during ACLS with conflicting results. However, patients with refractory cardiac arrest died in almost all cases without the availability of extracorporeal cardiopulmonary resuscitation (ECPR). Our aim was to determine if endotracheal intubation (ETI) was associated with improved outcomes compared to supraglottic airways (SGA) in patients with refractory cardiac arrest presenting for ECPR.

A phylogenetic study of dengue virus in urban Vietnam shows long-term persistence of endemic strains.

Dengue virus (DENV) causes repeated outbreaks of disease in endemic areas, with patterns of local transmission strongly influenced by seasonality, importation via human movement, immunity, and vector control efforts. An understanding of how each of these interacts to enable endemic transmission (continual circulation of local virus strains) is largely unknown. There are times of the year when no cases are reported, often for extended periods of time, perhaps wrongly implying the successful eradication of a local strain from that area.

White Paper: Best Practices in the Communication and Management of Actionable Incidental Findings in Emergency Department Imaging.

Purpose: Actionable incidental findings (AIFs) are common in radiologic imaging. Imaging is commonly performed in emergency department (ED) visits, and AIFs are frequently encountered, but the ED presents unique challenges for communication and follow-up of these findings. The authors formed a multidisciplinary panel to seek consensus regarding best practices in the reporting, communication, and follow-up of AIFs on ED imaging tests.

Racial or ethnic differences on treatment adherence and persistence among patients with inflammatory bowel diseases initiated with biologic therapies.

Background: Inflammatory bowel disease (IBD) is a chronic disease with the potential for significant morbidity in case of suboptimal treatment (e.g. low treatment adherence).

Amivantamab, an Epidermal Growth Factor Receptor (EGFR) and Mesenchymal-epithelial Transition Factor (MET) Bispecific Antibody, Designed to Enable Multiple Mechanisms of Action and Broad Clinical Applications.

Substantial therapeutic advancements have been made in identifying and treating activating mutations in advanced non-small cell lung cancer (NSCLC); however, resistance to epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) inhibitors remains common with current targeted therapies. Amivantamab, a fully human bispecific antibody targeting EGFR and MET, is approved in the United States and other countries for the treatment of patients with advanced NSCLC with EGFR exon 20 insertion mutations, for whom disease has progressed on or after platinum-based chemotherapy. Preliminary efficacy and safety have also been demonstrated in patients with common EGFR- or MET-mutated NSCLC.

Practical considerations for navigating the regulatory landscape of non-clinical studies for clinical translation of radiopharmaceuticals.

Background: The development of radiopharmaceuticals requires extensive evaluation before they can be applied in a diagnostic or therapeutic setting in Nuclear Medicine. Chemical, radiochemical, and pharmaceutical parameters must be established and verified to ensure the quality of these novel products.

Main Body: To provide supportive evidence for the expected human in vivo behaviour, particularly related to safety and efficacy, additional tests, often referred to as "non-clinical" or "preclinical" are mandatory.

Complications rate of surgically assisted endoscopic retrograde cholangiopancreatography.

Background: With the rise in obesity and gastric bypass procedures, the normal anatomy and approach for endoscopic retrograde cholangiopancreatography (ERCP) is eliminated. Surgically assisted ERCP is the standard technique to access the biliary system and perform ERCP in these patients. These patients are at increased risk for cholelithiasis.

A Chemical Strategy toward Novel Brain-Penetrant EZH2 Inhibitors.

Aberrant gene-silencing through dysregulation of polycomb protein activity has emerged as an important oncogenic mechanism in cancer, implicating polycomb proteins as important therapeutic targets. Recently, an inhibitor targeting EZH2, the methyltransferase component of PRC2, received U.S.

Severe Referred Shoulder Pain Following Revision Fundoplication From a Stich on the Diaphragm.

Complications following fundoplication surgery for hiatal hernias are rare. Herein, we present the case of a 61-year-old woman who underwent a Nissen fundoplication, complicated by dysphagia, and a revision modified Toupet fundoplication for a hiatal hernia, after which she began to experience severe prandial referred left shoulder pain that was refractory to medical management. We hypothesized that a diaphragmatic suture placed during the revision fundoplication could be the source of the pain, and we elected to remove the suture, resulting in resolution of the pain.

The Minnesota mobile extracorporeal cardiopulmonary resuscitation consortium for treatment of out-of-hospital refractory ventricular fibrillation: Program description, performance, and outcomes.

Background: We describe implementation, evaluate performance, and report outcomes from the first program serving an entire metropolitan area designed to rapidly deliver extracorporeal membrane oxygenation (ECMO)-facilitated resuscitation to patients with refractory ventricular fibrillation/ventricular tachycardia (VF/VT) out-of-hospital cardiac arrest (OHCA).

Methods: This observational cohort study analyzed consecutive patients prospectively enrolled in the Minnesota Mobile Resuscitation Consortium's ECMO-facilitated resuscitation program. Entry criteria included: 1) adults (aged 18-75), 2) VF/VT OHCA, 3) no return of spontaneous circulation following 3 shocks, 4) automated cardiopulmonary resuscitation with a Lund University Cardiac Arrest System (LUCAS™), and 5) estimated transfer time of < 30 min.

Physician assistants in geriatric medical care.

Background: The US population is maturing. As of 2020, over 52 million (16%) people are age 65 or older. With a citizenry that is increasingly "gray," the nation is short of medical providers who specialize in geriatric medical care.

Bivalent binding on cells varies between anti-CD20 antibodies and is dose-dependent.

Based on their mechanism of action, two types of anti-CD20 antibodies are distinguished: Type I, which efficiently mediate complement-dependent cytotoxicity, and Type II, which instead are more efficient in inducing direct cell death. Several molecular characteristics of these antibodies have been suggested to underlie these different biological functions, one of these being the manner of binding to CD20 expressed on malignant B cells. However, the exact binding model on cells is unclear.

A real-time cell-binding assay reveals dynamic features of STxB-Gb3 cointernalization and STxB-mediated cargo delivery into cancer cells.

The interaction between the Shiga toxin B-subunit (STxB) and its globotriaosylceramide receptor (Gb3) has a high potential for being exploited for targeted cancer therapy. The primary goal of this study was to evaluate the capacity of STxB to carry small molecules and proteins as cargo into cells. For this purpose, an assay was designed to provide real-time information about the StxB-Gb3 interaction as well as the dynamics and mechanism of the internalization process.

Novel Pure αVβ3 Integrin Antagonists That Do Not Induce Receptor Extension, Prime the Receptor, or Enhance Angiogenesis at Low Concentrations.

The integrin αVβ3 receptor has been implicated in several important diseases, but no antagonists are approved for human therapy. One possible limitation of current small-molecule antagonists is their ability to induce a major conformational change in the receptor that induces it to adopt a high-affinity ligand-binding state. In response, we used structural inferences from a pure peptide antagonist to design the small-molecule pure antagonists TDI-4161 and TDI-3761.

Operational strategies in US cancer centers of excellence that support the successful accrual of racial and ethnic minorities in clinical trials.

Background: Study populations in clinical research must reflect US changing demographics, especially with the rise of precision medicine. However, racial and ethnic minority groups (REMGs) have low rates of participation in cancer clinical trials.

Methods: Criteria were developed to identify cancer centers able to accrue a higher than average proportion of REMGs into clinical trials.

Morehouse Choice Accountable Care Organization and Education System (MCACO-ES): Integrated Model Delivering Equitable Quality Care.

Accountable Care Organizations (ACOs) seek sustainable innovation through the testing of new care delivery methods that promote shared goals among value-based health care collaborators. The Morehouse Choice Accountable Care Organization and Education System (MCACO-ES), or (M-ACO) is a physician led integrated delivery model participating in the Medicare Shared Savings Program (MSSP) offered through the Centers for Medicare and Medicaid Services (CMS) Innovation Center. The MSSP establishes incentivized, performance-based payment models for qualifying health care organizations serving traditional Medicare beneficiaries that promote collaborative efficiency models designed to mitigate fragmented and insufficient access to health care, reduce unnecessary cost, and improve clinical outcomes.