Research Spotlight

Johannesson, L., Testa, G., Putman, J.M., McKenna, G.J., Koon, E.C., York, J.R., Bayer, J., Zhang, L., Rubeo, Z.S., Gunby, R.T. and Gregg, A.R. (2021). “Twelve Live Births After Uterus Transplantation in the Dallas UtErus Transplant Study.” Obstet Gynecol 137(2): 241-249.

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OBJECTIVE: To describe aggregated pregnancy outcomes after uterus transplantation from a single, experienced center. METHODS: This prospective study reports on live births among 20 women who received a uterus transplant from 2016 to 2019 at Baylor University Medical Center at Dallas. These live births occurred between November 2017 and September 2020. The main measures were live birth, maternal complications, and fetal and newborn outcomes. RESULTS: There were six graft failures (four surgical complications and two with poor perfusion postoperatively). Of the 14 technically successful transplants, at least one live birth occurred in 11 patients. Thus far, the live birth rate per attempted transplant is 55%, and the live-birth rate per technically successful transplant is 79%. Ten uteri were from nondirected living donors and one uterus was from a deceased donor. In vitro fertilization was performed to achieve pregnancy. Ten recipients delivered one neonate, and one recipient delivered two neonates. One organ rejection episode was detected during pregnancy and was resolved with steroids. The median birth weight was 2,890 g (range 1,770-3,140 g [median 68th percentile]). Maternal weight gain was higher than Institute of Medicine recommendations. Maternal medical complications were observed in five recipients (elevated creatinine level, gestational diabetes, gestational hypertension [n=2], and preeclampsia). In five recipients, maternal medical or obstetric complications led to an unplanned preterm delivery (elevated creatinine level, preeclampsia; preterm labor [n=3]). The median gestational age at delivery was 36 6/7 weeks (range 30 6/7-38 weeks). All neonates were liveborn, with Apgar scores of 8 or higher at 5 minutes. CONCLUSION: Over the first 3 years, our program experienced a live-birth rate per attempted transplant of 55% and a live-birth rate per technically successful transplant of 79%. In our experience, uterus transplantation resulted in a third-trimester live birth in all cases in which pregnancies reached 20 weeks of gestation. Maternal medical and obstetric complications can occur; however, these were manageable by applying principles of generally accepted obstetric practice.

Jacob, A., Shook, J. and Hutson, T. (2021). “The implementation of lenvatinib/everolimus or lenvatinib/pembrolizumab combinations in the treatment of metastatic renal cell carcinoma.” Expert Rev Anticancer Ther Jan 6;1-8. [Epub ahead of print]. 1-8.

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Introduction: There are 400,000 new cases of Renal Cell Carcinoma (RCC) and 175,000 deaths worldwide every year. Currently available frontline therapies to treat RCC have less toxicity than previously employed therapeutic agents, but drug resistance is still a clinically significant problem. Drug resistance occurs through angiogenic escape by the activation of pathways that are independent of the VEGF targets of most first-line therapies. The lenvatinib/everolimus and lenvatinib/pembrolizumab are part of a new generation of combinations that can combat this method of resistance to extend both progression-free survival and overall survival in patients with metastatic RCC. Areas covered: This article discusses the evolution of current data on the efficacy and safety of these two combinations and future directions for their implementation in the treatment of advanced renal cell carcinoma. Expert opinion: Future research will focus on these combinations in contrast with other currently approved regimens. Once specific biomarkers that predict response to treatment are identified, the future of treatment of mRCC will involve specifically tailored therapies for a patient’s genotype. Therapies unique only to the patient undergoing treatment will increase both efficacy and safety of new treatments, and that is the truly exciting future that awaits this field.

Soto, J.M., Feng, D., Sun, H., Zhang, Y., Lyon, K.A., Liang, B., Reed, L.K. and Huang, J.H. (2021). “Novel Decompressive Hemicraniectomy Technique for Traumatic Brain Injury: Technical Note.” World Neurosurg 146: 15-19.

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BACKGROUND: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality across all age groups. Decompressive hemicraniectomy is the treatment for TBI-related refractory intracranial hypertension. The traditional technique for this procedure can result in wound complications due to injury of the scalp flap’s vascular supply, namely the superficial temporal and postauricular arteries. METHODS: In this technical note we describe our experience using a novel technique that preserves both vascular territories by placing the inferior aspect of the incision posterior to the ear as opposed to anterior to it. This modification has the potential to reduce wound healing complications, especially in those at higher risk, while also reducing operative time by avoiding temporalis muscle incision and closure during procedure. RESULTS: After performing hospital chart review, a total of 7 patients were found who underwent this hemicraniectomy technique for severe TBI. Of these, 5 patients had this performed on the left side, and 2 patients had this performed on the right side. Six of the patients had an accompanying subdural hematoma, whereas 1 patient had no intracranial hemorrhage present. CONCLUSIONS: In each case, both the superficial temporal and postauricular arteries were preserved, and rapid healing of the scalp flap occurred. In addition to providing a large bone window to allow the brain to swell, this technique has the potential to reduce complications of wound healing by preserving the vascular supply of the scalp flap and reduce operative times by minimizing temporalis muscle dissection.

Wen, W., Li, P., Liu, P., Xu, S., Wang, F. and Huang, J.H. (2021). “Post-Translational Modifications of BACE1 in Alzheimer’s Disease.” Curr Neuropharmacol Jan 21. [Epub ahead of print].

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Beta-Amyloid Cleaving Enzyme1 (BACE1) is a monospecific enzyme for the key rate-limiting step in the synthesis of beta-amyloid(Aβ) from cleavage of amyloid precursor protein (APP), to form senile plaques and causes cognitive dysfunction in Alzheimer’s disease (AD). Post-translation modifications of BACE1, such as acetylation, glycosylation, palmitoylation, phosphorylation, play a crucial role in the trafficking and maturation process of BACE1. The study of BACE1 is of great importance not only for understanding the formation of toxic Aβ but also for the development of an effective therapeutic target for the treatment of AD. This paper review recent advances in the studies about BACE1, with focuses being paid to the relationship of Aβ, BACE1 with post-translational regulation of BACE1. In addition, we specially reviewed studies about the compounds that can be used to affect post-translational regulation of BACE1 or regulate BACE1 in the literature, which can be used for subsequent research on whether BACE1 is a post-translationally modified drug.

Ma, T., Wang, F., Xu, S. and Huang, J.H. (2021). “Meningeal immunity: Structure, function and a potential therapeutic target of neurodegenerative diseases.” Brain Behav Immun Feb 4;S0889-1591(21)00032-5. [Epub ahead of print].

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Meningeal immunity refers to immune surveillance and immune defense in the meningeal immune compartment, which depends on the unique position, structural composition of the meninges and functional characteristics of the meningeal immune cells. Recent research advances in meningeal immunity have demonstrated many new ways in which a sophisticated immune landscape affects central nervous system (CNS) function under physiological or pathological conditions. The proper function of the meningeal compartment might protect the CNS from pathogens or contribute to neurological disorders. Since the concept of meningeal immunity, especially the meningeal lymphatic system and the glymphatic system, is relatively new, we will provide a general review of the meninges’ basic structural elements, organization, regulation, and functions with regards to meningeal immunity. At the same time, we will emphasize recent evidence for the role of meningeal immunity in neurodegenerative diseases. More importantly, we will speculate about the feasibility of the meningeal immune region as a drug target to provide some insights for future research of meningeal immunity.