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Lung transplant recipient populations evolve with advances in medical therapies

Cystic fibrosis (CF) and pulmonary hypertension (PH) were once common categories for referral to lung transplant. However, advances in medical therapies have allowed many patients with these diseases to avoid transplant. Today, at most transplant centers throughout the world, lung transplants are being performed on increasingly older patients, primarily with interstitial lung disease (ILD) followed by chronic obstructive pulmonary disease (COPD).  Unlike CF and PH, few treatments with the ability to extend survival currently exist for ILD, specifically idiopathic pulmonary fibrosis (IPF), and COPD. When these patients continue to decline despite maximized medical therapy, surgical options may be indicated.

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Lung transplantation in the context of COVID-19-induced chronic lung disease

Editorial by Todd Grazia, MD, Chief of Transplant Pulmonology, Baylor University Medical Center

When SARS Co-V2 arrived on U.S. shores in early 2020, physicians in all specialties faced an enormous learning curve. As many have said, we didn’t know what we didn’t know about the coronavirus. Some patients seemed to skate through the infection, while others were laid up with flu-like symptoms for a few weeks, and yet others developed severe respiratory failure from ARDS and died. Pulmonologists and intensivists were tasked with caring for and trying to treat a critical patient population whose lungs seemed to be systematically attacked, and often, permanently damaged by the virus. As the pandemic continued to rage and upend lives, transplant pulmonologists faced a daunting ethical dilemma: Should we or should we not consider lung transplantation for patients with irreversible lung damage from COVID-19?

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Antibacterial “envelope” found to help reduce CIED infections

Findings of a clinical study demonstrated that the use of an antibiotic-eluting envelope placed around a cardiac implantable electronic device (CIED) during implantation reduced the incidence of major infections by 40 percent compared implantation without the antibacterial envelop. The study, called the Worldwide Randomized Antibiotic Envelope Infection Prevention Trial (WRAP-IT; NCT02277990), evaluated the safety and efficacy of the Medtronic TYRXTM Absorbable Antibacterial Envelope in adult patients at 181 centers in 25 countries with 776 implanting physicians.

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New insights into immunotherapy for autoimmune demyelinating diseases

Dendritic cell vaccines are becoming an important part of the immunotherapy toolkit for a wide range of diseases, including cancer, infectious disease, and autoimmunity. Dendritic cells are potent antigen presenting cells that can either stimulate or suppress immune response depending on their maturation state. By targeting key myelin protein to immature dermal dendritic cells, a group of researchers, including the laboratory of Gerard Zurawski, PhD, director of the Center for Biotechnology in the Baylor Scott & White Research Institute, part of Baylor Scott & White Health, have shown promising pre-clinical results for a candidate dendritic cell vaccine against demyelinating diseases.

Their recent manuscript, published in The Lancet EBioMedicine in September 2019, provides proof-of-principle that a dendritic cell vaccine can reduce autoimmunity in a cynomolgus-macaque model of experimental autoimmune encephalomyelitis (EAE), which is a primate model system for studying inflammatory demyelinating diseases. This work suggests that the vaccine could move forward to human trials.

Acute demyelinating diseases are a suite of debilitating neurological conditions. Although multiple sclerosis is the most well-studied demyelinating disease, there are other related disorders that rely on the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG) and respond poorly to therapies targeted at multiple sclerosis. They include acute disseminated encephalomyelitis, optic neuritis, and neuromyelitis optica spectrum disorder. By strengthening immune tolerance to MOG, it is possible that these demyelinating diseases can be cured.

The team took advantage of the insight that immature dermal dendritic cells can promote immune tolerance. The tolerogenic DC-asialoglycoprotein receptor (DC-ASGPR) allows antigens to enter dendritic cells and be processed for presentation to T cells. Therefore, they created an antibody to DC-ASGPR that was attached to the MOG protein (anti-DC-ASGPR-MOG), which allowed the MOG protein to be processed and presented to T cells to induce immune tolerance.

They found that exposure to anti-DC-ASGPR-MOG prevented the appearance of behavioral and neurological deficits associated with EAE. Anti-DC-ASGPR-MOG also suppressed immune activation, including reducing CD4+ T cell activation and suppressing proinflammatory cytokine production. In addition, the treatment induced a population of circulating MOG-specific regulatory T lymphocytes and induced the cytokine TGF-beta, all of which support existing models for mechanisms of preventing autoimmunity.

Development of the immunotherapeutic products was supported by Baylor Scott & White Healthcare system funding. Members of the research team are also inventors on a patent that is pending for the use of DC-ASGPR targeting immunotherapeutics in demyelinating diseases. The Transfer Technology Office at Baylor Scott & White Research Institute collaborates with inventors throughout the discovery and development process to evaluate, patent, market, and manage the licenses for technology developed through BSWRI. They serve as a single point of contact for innovations across the Baylor Scott & White system, thereby creating efficient workflows.

ECMO allows patient with COVID-19-induced myocarditis to completely recover

Although relatively rare, there have been several case reports of COVID-19 infection causing acute myocarditis. These patients have required IV inotrope therapy and sometimes short-term veno-arterial ECMO support for bi-ventricular shock. Such was the case with a 64-year-old female patient from San Antonio who was successfully treated at Baylor University Medical Center.

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