Purpose of Review: H3K27M is a frequent histone mutation within diffuse midline gliomas and is associated with a dismal prognosis, so much so that the 2016 CNS WHO classification system created a specific category of "Diffuse Midline Glioma, H3K27M-mutant". Here we outline the latest pre-clinical data and ongoing current clinical trials that target H3K27M, as well as explore diagnosis and treatment monitoring by serial liquid biopsy.
RecentFindings: Multiple epigenetic compounds have demonstrated efficacy and on-target effects in pre-clinical models. The imipridone ONC201 and the IDO1 inhibitor indoximod have demonstrated early clinical activity against H3K27M-mutant gliomas. Liquid biopsy of cerebrospinal fluid has shown promise for clinical use in H3K27M-mutant tumors for diagnosis and monitoring treatment response.Summary: While H3K27M has elicited a widespread platform of pre-clinical therapies with promise, much progress still needs to be made to improve outcomes for diffuse midline glioma patients. We present current treatment and monitoring techniques as well as novel approaches in identifying and targeting H3K27M-mutant gliomas.
We are in the midst of exciting times from a demographic standpoint as the population of darker-skinned people grows exponentially in the United States. Although there is a growing demand for facial cosmetic procedures amongst people of color, the total number of individuals undergoing surgical facial rejuvenation is dwarfed by the current Caucasian market. In order to provide optimal options for facial rejuvenation, cosmetic surgeons must have an underlying appreciation for the dynamic interplay among ethnicity, facial morphology, and the progression of aging. The purpose of the present article is to outline the minimally invasive surgical options for facial rejuvenation best suited for the patient of color. Although the population of individuals with darker-pigmented skin is quite vast, the present paper will focus on individuals of African descent, with whom the author has the most experience. Preferred surgical techniques include blepharoplasty, autologous facial fat transplantation, percutaneous cheek lift, and submental liposuction. Cutaneous surgeons familiar with soft-tissue surgery and facial anatomy should feel comfortable performing these techniques.
Background. Human papillomavirus (HPV) represents a potential risk factor for squamous cell cancer of the head and neck (SCCHN). We evaluated the prevalence of HPV DNA in patients with SCCHN diagnosed at the University of Michigan from 1994-1996. Methods. Patients were stratified by age at diagnosis as "young" (<50 years; median, 39) or "old" (>50 years; median, 66). Fourteen "young" and 14 "old" were matched for tumor site, and 4 additional "old" patients were included. Specimens were analyzed by polymerase chain reaction for HPV DNA using 2 sets of consensus primers. HPV sequences were confirmed by Southern blot hybridization and typed with type-specific probes.Results. Overall, 15 of 32 (46.9%) samples contained HPV sequences. HPV 16 was detected in 9 of 15 (60%), HPV-18 in 1 of 15 (6.6%), and 5 of 15 (33.3%) remained untyped by multiple methods. When stratified, 7 of 14 (50%) "young" were HPVpositive compared with 8 of 18 (44.4%) "old" (p = .76). Survival in patients with HPV-positive SCCHN was significantly longer than that for HPV-negative patients.Conclusions. The incidence of HPV in "young" versus "old" is not significantly different, suggesting similar roles for both groups. Patients with HPV-positive tumors may have a survival advantage relative to patients with HPV-negative tumors.
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