Venovenous ECMO for Acute Chronic Heart Failure after Bilateral Lung Transplantation.

ABSTRACT: Venovenous (VV) ECMO is rarely used during decompensated circulatory states. Although VA ECMO is the routine option, VV ECMO may be an option in selected patients. We present a case of pulmonary edema due to acute heart failure in a patient 4- and 12-year post-lung transplantation who received VV ECMO. Using a thoughtful cannulation strategy, VV ECMO, and aggressive ultrafiltration, the patient was successfully decannulated, extubated, and discharged from the hospital. In cardiogenic pulmonary edema, VV ECMO represents an additional, and likely under-utilized tool, especially in patients who are at high risk for ventilator-associated lung injury. Cannula location and size should be given additional consideration to potentially transition to V-AV ECMO configuration if necessary.

Sequential intravenous and intracerebroventricular GD2-CAR T-cell therapy for H3K27M-mutated diffuse midline gliomas.

H3K27M-mutant diffuse midline gliomas (DMGs) express high levels of the GD2 disialoganglioside and chimeric antigen receptor modified T-cells targeting GD2 (GD2-CART) eradicate DMGs in preclinical models. Arm A of the Phase I trial NCT04196413 administered one IV dose of autologous GD2-CART to patients with H3K27M-mutant pontine (DIPG) or spinal (sDMG) diffuse midline glioma at two dose levels (DL1=1e6/kg; DL2=3e6/kg) following lymphodepleting (LD) chemotherapy. Patients with clinical or imaging benefit were eligible for subsequent intracerebroventricular (ICV) GD2-CART infusions (10-30e6 GD2-CART). Primary objectives were manufacturing feasibility, tolerability, and identification of a maximally tolerated dose of IV GD2-CART. Secondary objectives included preliminary assessments of benefit. Thirteen patients enrolled and 11 received IV GD2-CART on study [n=3 DL1(3 DIPG); n=8 DL2(6 DIPG/2 sDMG). GD2-CART manufacturing was successful for all patients. No dose-limiting toxicities (DLTs) occurred on DL1, but three patients experienced DLT on DL2 due to grade 4 cytokine release syndrome (CRS). Nine patients received ICV infusions, which were not associated with DLTs. All patients exhibited tumor inflammation-associated neurotoxicity (TIAN). Four patients demonstrated major volumetric tumor reductions (52%, 54%, 91% and 100%). One patient exhibited a complete response ongoing for >30 months since enrollment. Eight patients demonstrated neurological benefit based upon a protocol-directed Clinical Improvement Score. Sequential IV followed by ICV GD2-CART induced tumor regressions and neurological improvements in patients with DIPG and sDMG. DL1 was established as the maximally tolerated IV GD2-CART dose. Neurotoxicity was safely managed with intensive monitoring and close adherence to a management algorithm.

Enhancing pediatric access to cell and gene therapies.

Increasing numbers of cell and gene therapies (CGTs) are emerging to treat and cure pediatric diseases. However, small market sizes limit the potential return on investment within the traditional biopharmaceutical drug development model, leading to a market failure. In this Perspective, we discuss major factors contributing to this failure, including high manufacturing costs, regulatory challenges, and licensing practices that do not incorporate pediatric development milestones, as well as potential solutions. We propose the creation of a new entity, the Pediatric Advanced Medicines Biotech, to lead late-stage development and commercialize pediatric CGTs outside the traditional biopharmaceutical model in the United States-where organized efforts to solve this problem have been lacking. The Pediatric Advanced Medicines Biotech would partner with the academic ecosystem, manufacture products in academic good manufacturing practice facilities and work closely with regulatory bodies, to ferry CGTs across the drug development 'valley of death' and, ultimately, increase access to lifesaving treatments for children in need.

Emergency Clinician Experiences Using a Standardized Communication Tool for Cardiac Arrest.

Introduction Sudden cardiac arrest remains a common and critical disease burden. As post-cardiac arrest care grows in complexity, communication between pre-hospital providers, emergency department personnel, and hospital consultants is increasingly important. Methods This study evaluated the use of a standard handoff tool between pre-hospital personnel and hospital staff, including emergency medical services (EMS), emergency department nurses, physicians, and cardiologists. Personnel were surveyed regarding attitudes surrounding the important aspects of cardiac arrest care, challenges faced, and preference of handoff mechanism. Results Most of the survey respondents (58, 76%) found that the initial rhythm was the most important factor in post-cardiac arrest care, followed by the presence of bystander cardiopulmonary resuscitation (CPR; 55, 72%) and the presence of ST-elevation on initial electrocardiogram (46, 61%). Both emergency physicians (7, 63%), as well as cardiologists (3, 100%), preferred to have this tool performed over radio prior to arrival in the emergency department. Conclusion The importance given to various post-cardiac arrest factors varied amongst specialty and clinical background; however, all agreed on common features such as the initial rhythm, electrocardiogram (ECG) morphology, and the presence or absence of bystander CPR. Additionally, the timing and structure of how this information is delivered were further elucidated. This data will guide future handoff methods between specialties managing patients after cardiac arrest.

Acidemia Detected on Venous Blood Gas After Out-of-Hospital Cardiac Arrest Predicts Likelihood to Survive to Hospital Discharge.

BACKGROUND: Sudden cardiac arrest is the most common cause of death worldwide, and prognostication after survival remains challenging. Decisions regarding prognosis can be fraught with error in the immediate postarrest period, with guidelines recommending the use of various tests, including blood gas pH, to determine which interventions to perform. Despite these recommendations, the prognostic utility of blood gas pH remains unclear. OBJECTIVES: In this retrospective cohort study, we aimed to demonstrate the prognostic utility of emergency department blood gas pH after return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest. METHODS: A retrospective cohort study was performed, including all adult survivors of out-of-hospital cardiac arrest (n = 79). Primary disease-oriented outcome was venous blood pH after ROSC and survival to hospital discharge. RESULTS: In patients with out-of-hospital cardiac arrest, pH < 7.2 was associated with decreased likelihood of survival to hospital discharge (odds ratio 0.06), with every 0.1-unit increase in pH being associated with an increased likelihood of survival (1.98). Based on the area under the receiver curve, the pH that optimizes sensitivity and specificity for predicting survival was 7.04. CONCLUSION: Both presence and degree of acidemia on initial blood gas after ROSC was associated with a decreased likelihood of survival to hospital discharge. The optimal cutoff for prediction in this cohort of patients was 7.04. Using a higher pH cutoff would result in fewer patients receiving intervention that would otherwise have survived.

Mechanical ventilation of pediatric patients in the emergency department.

When pediatric patients require mechanical ventilation in the emergency department, the emergency clinician should be prepared to select initial ventilator settings and respond to an intubated patient's dynamic physiologic needs to ensure ongoing oxygenation, ventilation, and hemodynamic stability. Pressure-targeted ventilation is generally recommended in pediatric patients, with initial ventilator settings varying depending on age and the etiology of respiratory failure. This issue reviews indications for mechanical ventilation and offers recommendations for ventilator settings and dosing of analgesics, sedatives, and neuromuscular blockers, with a focus on patient populations in whom the approach to mechanical ventilation may be different.

Diagnosis of Rectus Sheath Hematoma by Point-of-Care Ultrasound.

BACKGROUND: Rectus sheath hematoma is a rare but dangerous cause of undifferentiated hypotension and abdominal pain in the emergency department (ED). Point-of-care ultrasound is a useful tool in its identification. CASE REPORT: A 75-year-old woman presented to the ED with hypotension of an unclear etiology. She was found, via point-of-care ultrasound, to have a large and expanding rectus sheath hematoma. She ultimately had embolization of a lacerated epigastric artery, likely caused by enoxaparin injection. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Rectus sheath hematomas are a dangerous and often unrecognized source of abdominal pain and shock in anticoagulated patients. Commonly applied point-of-care ultrasound algorithms to assess hypotension may miss this entity.

Increasing Awareness on Health Care Access in Florida: A Community-Based Medical-Legal Practicum Project.

PROBLEM: Service learning and experiential coursework has become a requirement for medical students and law students. Advocacy for the underinsured and uninsured is of ethical importance to both the practice of law and medicine, however engaging professional students in meaningful advocacy work with community partners can be challenging. PURPOSE: The article describes a partnership between medical and law students in a community-based service learning project to promote health care access. KEY POINTS: Law and medical students at Florida International University partnered with community members and Florida Legal Services to collect patient narratives, disseminate information on Medicaid expansion to community members, and present patient stories to state lawmakers. CONCLUSIONS: The medical and law students learned about each other's professional roles and gained skills in interviewing, and legislative and policy advocacy through this service learning project by providing legislative testimony to key stakeholders and community education on Medicaid expansion.