Clinicians' Perspectives on Racism and Black Women's Maternal Health.

Objective: The objective of this study was to explore clinician perceptions of how racism affects Black women's pregnancy experiences, perinatal care, and birth outcomes. Materials and Methods: We conducted 25 semi-structured interviews with perinatal care clinicians practicing in the San Francisco Bay Area (January to March 2019) who serve racially diverse women. Participants were primarily recruited through "Dear Perinatal Care Provider" email correspondences sent through department listservs. Culturally concordant, qualitatively trained research assistants conducted all interviews in person. The interviews ranged from 30 to 60 minutes and were audio-recorded and professionally transcribed verbatim. We used the constant comparative method consistent with grounded theory to analyze data. Results: Most participants were obstetrician/gynecologists (n = 11, 44%) or certified nurse midwives (n = 8, 32%), had worked in their current role for 1 to 5 years (n = 10, 40%), and identified as white (n = 16, 64%). Three themes emerged from the interviews: provision of inequitable care (e.g., I had a woman who had a massive complication during her labor course and felt like she wasn't being treated seriously); surveillance of Black women and families (e.g., A urine tox screen on the Black baby even though it was not indicated, and they didn't do it on the white baby when, in fact, it was indicated); and structural care issues (e.g., the history of medical racial experimentation). Conclusion: Clinicians' views about how racism is currently operating and negatively impacting Black women's care experiences, health outcomes, and well-being in medical institutions will be used to develop a racial equity training for perinatal care clinicians in collaboration with Black women and clinicians.

Genomic risk prediction of aromatase inhibitor-related arthralgia in patients with breast cancer using a novel machine-learning algorithm.

Many breast cancer (BC) patients treated with aromatase inhibitors (AIs) develop aromatase inhibitor-related arthralgia (AIA). Candidate gene studies to identify AIA risk are limited in scope. We evaluated the potential of a novel analytic algorithm (NAA) to predict AIA using germline single nucleotide polymorphisms (SNP) data obtained before treatment initiation. Systematic chart review of 700 AI-treated patients with stage I-III BC identified asymptomatic patients (n = 39) and those with clinically significant AIA resulting in AI termination or therapy switch (n = 123). Germline DNA was obtained and SNP genotyping performed using the Affymetrix UK BioBank Axiom Array to yield 695,277 SNPs. SNP clusters that most closely defined AIA risk were discovered using an NAA that sequentially combined statistical filtering and a machine-learning algorithm. NCBI PhenGenI and Ensemble databases defined gene attribution of the most discriminating SNPs. Phenotype, pathway, and ontologic analyses assessed functional and mechanistic validity. Demographics were similar in cases and controls. A cluster of 70 SNPs, correlating to 57 genes, was identified. This SNP group predicted AIA occurrence with a maximum accuracy of 75.93%. Strong associations with arthralgia, breast cancer, and estrogen phenotypes were seen in 19/57 genes (33%) and were functionally consistent. Using a NAA, we identified a 70 SNP cluster that predicted AIA risk with fair accuracy. Phenotype, functional, and pathway analysis of attributed genes was consistent with clinical phenotypes. This study is the first to link a specific SNP/gene cluster to AIA risk independent of candidate gene bias.

Exploring Genetic Attributions Underlying Radiotherapy-Induced Fatigue in Prostate Cancer Patients.

CONTEXT: Despite numerous proposed mechanisms, no definitive pathophysiology underlying radiotherapy-induced fatigue (RIF) has been established. However, the dysregulation of a set of 35 genes was recently validated to predict development of fatigue in prostate cancer patients receiving radiotherapy. OBJECTIVES: To hypothesize novel pathways, and provide genetic targets for currently proposed pathways implicated in RIF development through analysis of the previously validated gene set. METHODS: The gene set was analyzed for all phenotypic attributions implicated in the phenotype of fatigue. Initially, a "directed" approach was used by querying specific fatigue-related sub-phenotypes against all known phenotypic attributions of the gene set. Then, an "undirected" approach, reviewing the entirety of the literature referencing the 35 genes, was used to increase analysis sensitivity. RESULTS: The dysregulated genes attribute to neural, immunological, mitochondrial, muscular, and metabolic pathways. In addition, certain genes suggest phenotypes not previously emphasized in the context of RIF, such as ionizing radiation sensitivity, DNA damage, and altered DNA repair frequency. Several genes also associated with prostate cancer depression, possibly emphasizing variable radiosensitivity by RIF-prone patients, which may have palliative care implications. Despite the relevant findings, many of the 35 RIF-predictive genes are poorly characterized, warranting their investigation. CONCLUSION: The implications of herein presented RIF pathways are purely theoretical until specific end-point driven experiments are conducted in more congruent contexts. Nevertheless, the presented attributions are informative, directing future investigation to definitively elucidate RIF's pathoetiology. This study demonstrates an arguably comprehensive method of approaching known differential expression underlying a complex phenotype, to correlate feasible pathophysiology.

Development and refinement of computer-assisted planning and execution system for use in face-jaw-teeth transplantation to improve skeletal and dento-occlusal outcomes.

PURPOSE OF REVIEW: To describe the development and refinement of the computer-assisted planning and execution (CAPE) system for use in face-jaw-teeth transplants (FJTTs). RECENT FINDINGS: Although successful, some maxillofacial transplants result in suboptimal hybrid occlusion and may require subsequent surgical orthognathic revisions. Unfortunately, the use of traditional dental casts and splints pose several compromising shortcomings in the context of FJTT and hybrid occlusion. Computer-assisted surgery may overcome these challenges. Therefore, the use of computer-assisted orthognathic techniques and functional planning may prevent the need for such revisions and improve facial-skeletal outcomes. SUMMARY: A comprehensive CAPE system for use in FJTT was developed through a multicenter collaboration and refined using plastic models, live miniature swine surgery, and human cadaver models. The system marries preoperative surgical planning and intraoperative execution by allowing on-table navigation of the donor fragment relative to recipient cranium, and real-time reporting of patient's cephalometric measurements relative to a desired dental-skeletal outcome. FJTTs using live-animal and cadaveric models demonstrate the CAPE system to be accurate in navigation and beneficial in improving hybrid occlusion and other craniofacial outcomes. Future refinement of the CAPE system includes integration of more commonly performed orthognathic/maxillofacial procedures.

Could the biological robustness of low level laser therapy (Photobiomodulation) impact its use in the management of mucositis in head and neck cancer patients.

Low level laser therapy (LLLT) has been noted to be effective in mitigating the development of oral mucositis among patients being treated with chemoradiation for cancers of the head and neck. To explain the biological basis for this observation we performed a comprehensive literature search. Our investigation identified a substantial number of LLLT-activated pathways that have been strongly associated with negative tumor outcomes including proliferation, invasion, angiogenesis, metastases and cancer-treatment resistance. In light of these findings, we suggest an investigational strategy to assure that LLLT's anti-mucositis efficacy is independent of its possible potential to enhance threatening tumor behaviors. Included are appropriate pre-clinical modeling, short- and long-term follow-up of LLLT-treated patients, and the requirement for consistency of LLLT parameters.

Optimizing Hybrid Occlusion in Face-Jaw-Teeth Transplantation: A Preliminary Assessment of Real-Time Cephalometry as Part of the Computer-Assisted Planning and Execution Workstation for Craniomaxillofacial Surgery.

BACKGROUND: The aesthetic and functional outcomes surrounding Le Fort-based, face-jaw-teeth transplantation have been suboptimal, often leading to posttransplant class II/III skeletal profiles, palatal defects, and "hybrid malocclusion." Therefore, a novel technology-real-time cephalometry-was developed to provide the surgical team instantaneous, intraoperative knowledge of three-dimensional dentoskeletal parameters. METHODS: Mock face-jaw-teeth transplantation operations were performed on plastic and cadaveric human donor/recipient pairs (n = 2). Preoperatively, cephalometric landmarks were identified on donor/recipient skeletons using segmented computed tomographic scans. The computer-assisted planning and execution workstation tracked the position of the donor face-jaw-teeth segment in real time during the placement/inset onto recipient, reporting pertinent hybrid cephalometric parameters from any movement of donor tissue. The intraoperative data measured through real-time cephalometry were compared to posttransplant measurements for accuracy assessment. In addition, posttransplant cephalometric relationships were compared to planned outcomes to determine face-jaw-teeth transplantation success. RESULTS: Compared with postoperative data, the real-time cephalometry-calculated intraoperative measurement errors were 1.37 ± 1.11 mm and 0.45 ± 0.28 degrees for the plastic skull and 2.99 ± 2.24 mm and 2.63 ± 1.33 degrees for the human cadaver experiments. These results were comparable to the posttransplant relations to planned outcome (human cadaver experiment, 1.39 ± 1.81 mm and 2.18 ± 1.88 degrees; plastic skull experiment, 1.06 ± 0.63 mm and 0.53 ± 0.39 degrees). CONCLUSION: Based on this preliminary testing, real-time cephalometry may be a valuable adjunct for adjusting and measuring "hybrid occlusion" in face-jaw-teeth transplantation and other orthognathic surgical procedures.