Severe Mucositis Secondary to Pembrolizumab: Reports of Two Cases, Review of the Literature, and an Algorithm for Management.

The indications for use of programed cell death receptor (PD-1) inhibitors to treat cancer continues to expand rapidly. Treatment with PD-1 inhibitors has been associated with numerous immune-mediated mucocutaneous side effects. Here, we report 2 cases of severe mucositis caused by the PD-1 inhibitor pembrolizumab and review the defining features of similar cases. Recognition of mucocutaneous toxicities of PD-1 inhibitors is increasingly important as their use continues to expand. A stepwise approach to diagnosis and management is also reviewed.

Early Effects of COVID-19 on Oral and Maxillofacial Surgery Residency Training-Results From a National Survey.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has had an immense impact on the healthcare industry. Oral and maxillofacial surgery (OMS) clinical practice uniquely exposes providers to COVID-19. The purpose of the present study was to understand the effect of the COVID-19 pandemic on OMS residency training programs (OMSRTPs): 1) training and education; 2) availability and use of personal protective equipment (PPE); 3) experience with, and use of, screening and viral testing; 4) resident experience; and 5) program director (PD) experience and observations of the immediate and future effects on OMSRTPs. MATERIALS AND METHODS: OMS residents and PDs in OMSRTPs in the United States were invited to participate in the present cross-sectional study from April 1, 2020 to May 1, 2020. A 51-question survey was used to evaluate the effects of COVID-19 on OMSRTPs and to assess the 5 specific aims of the present study. RESULTS: A total of 160 residents and 13 PDs participated in the survey, representing 83% of US states or territories with OMSRTPs. Almost all residents (96.5%) reported modifications to their training program, and 14% had been reassigned to off-service clinical rotations (eg, medicine, intensive care unit). The use of an N95 respirator mask plus standard PPE precautions during aerosol-generating procedures varied by procedure location, with 36.8% reporting limited access to these respirators. Widespread screening practices were in use, with 83.6% using laboratory-based viral testing. Residents scheduled to graduate in 2022 were most concerned with the completion of the graduation requirements and with decreased operative experience. Most residents (94.2%) had moved to web-based didactics, and a plurality (47%) had found increased value in the didactics. CONCLUSIONS: Sweeping alterations to OMS clinical practice have occurred for those in OMSRTPs during the COVID-19 pandemic. Although the overall OMSRTP response has been favorable, residents' concerns regarding the ubiquitous availability of appropriate PPE, operative experience, and completion of graduation requirements requires further deliberation.

The Function of Twisted Gastrulation in Regulating Osteoclast Differentiation is Dependent on BMP Binding.

Proper regulation of osteoclast (OCL) function is critical for normal bone homeostasis. Bone morphogenetic protein (BMP) signaling and its regulation have been shown to have direct effects on OCL differentiation and activity. One of the major modulators of BMP signaling in the extracellular space is the secreted protein twisted gastrulation (TWSG1), which can inhibit BMP signaling and OCL differentiation. In this study we examine specific N-terminal regions of TWSG1 protein that have been previously proposed as BMP binding sites to determine whether TWSG1 binding to BMPs is required for its inhibitory effects on OCLs. We demonstrate that overexpression of wild type TWSG1 suppresses osteoclastogenesis, while overexpression of mutant TWSG1 proteins (W66A and N80Q/N146Q mutants), which cannot bind BMPs, leads to increased BMP signaling, enhanced osteoclastogenesis, increased resorptive activity, and expression of OCL-specific genes. Our results show that BMP binding is required for TWSG1-mediated inhibition of OCL formation and function, and validate the critical functional regions within the TWSG1 protein for these interactions.

Bone morphogenetic proteins: Their role in regulating osteoclast differentiation.

The ability to create recombinant bone morphogenetic proteins (BMPs) in recent years has led to their rise as a common clinical adjuvant. Their application varies, from spinal fixation to repairing palatal clefts, to coating implants for osseointegration. In recent years questions have been raised as to the efficacy of BMPs in several of these procedures. These questions are due to the unwanted side effect of BMPs on other cell types, such as osteoclasts which can resorb bone at the graft/implant site. However, most BMP research focuses on the anabolic osteoinductive effects of BMPs on osteoblasts rather than its counterpart- stimulation of the osteoclasts, which are cells responsible for resorbing bone. In this review, we discuss the data available from multiple in-vitro and in-vivo BMP-related knockout models to elucidate the different functions BMPs have on osteoclast differentiation and activity.