Patterns of recurrence in head and neck squamous cell carcinoma to inform personalized surveillance protocols.

BACKGROUND: Development of evidence-based post-treatment surveillance guidelines in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is limited by comprehensive documentation of patterns of recurrence and metastatic spread. METHODS: A retrospective analysis of patients diagnosed with R/M HNSCC at a National Cancer Institute-designated cancer center between 1998- 2019 was performed (n = 447). Univariate and multivariate analysis identified patterns of recurrence and predictors of survival. RESULTS: Median overall survival (mOS) improved over time (6.7 months in 1998-2007 to 11.8 months in 2008-2019, p = .006). Predictors of worse mOS included human papillomavirus (HPV) negativity (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.2-2.6), high neutrophil/lymphocyte ratio (HR, 2.1 [1.4-3.0], disease-free interval (DFI) ≤6 months (HR, 1.4 [1.02-2.0]), and poor performance status (Eastern Cooperative Oncology Group, ≥2; HR, 1.91.1-3.4). In this cohort, 50.6% of recurrences occurred within 6 months of treatment completion, 72.5% occurred within 1 year, and 88.6% occurred within 2 years. Metachronous distant metastases were more likely to occur in patients with HPV-positive disease (odds ratio [OR], 2.3 [1.4-4.0]), DFI >6 months (OR, 2.4 [1.5-4.0]), and body mass index ≥30 (OR, 2.3 [1.1-4.8]). Oligometastatic disease treated with local ablative therapy was associated with improved survival over polymetastatic disease (HR, 0.36; 95% CI, 0.24-0.55). CONCLUSION: These data regarding patterns of distant metastasis in HNSCC support the clinical utility of early detection of recurrence. Patterns of recurrence in this population can be used to inform individualized surveillance programs as well as to risk-stratify eligible patients for clinical trials. PLAIN LANGUAGE SUMMARY: After treatment for head and neck cancer (HNC), patients are at risk of recurrence at prior sites of disease or at distant sites in the body. This study includes a large group of patients with recurrent or metastatic HNC and examines factors associated with survival outcomes and recurrence patterns. Patients with human papillomavirus (HPV)-positive HNC have good survival outcomes, but if they recur, this may be in distant regions of the body and may occur later than HPV-negative patients. These data argue for personalized follow-up schedules for patients with HNC, perhaps incorporating imaging studies or novel blood tests.

Taking the burden off: a study of the quality of ethics consultation in the time of COVID-19.

BACKGROUND: The quality of ethics consults is notoriously difficult to measure. Survey-based assessments cannot capture nuances of consultations. To address this gap, we conducted interviews with health professionals who requested ethics consults during the initial phase of the COVID-19 pandemic. METHOD: Healthcare professionals requesting ethics consultation between March 2020 and May 2020 at a tertiary academic medical centre were eligible to participate. We asked participants to comment on the consults they called and thematically analysed responses to identify features associated with optimal quality consultations. RESULTS: Of 14 healthcare providers, 8 (57%) were women and professions were as follows: 11 (79%) medical doctors, 1 (7%) social worker, 1 (7%) physician assistant and 1 (7%) nurse practitioner. Two aspects of quality emerged: satisfaction and value. Themes within the domain of satisfaction included: responsiveness of the ethics consultant, willingness to consult, institutional role of the ethics service and identifying areas for improvement. When describing value, respondents spoke of the intrapersonal and interpersonal worth of consultation. CONCLUSION: Participants were generally satisfied with ethics consultation services, similar to opinions of those found in pre-COVID-19 survey studies. Our qualitative approach allowed for a richer exploration of the value of ethics consultation during the pandemic and has implications for ethics consultation services more broadly. Ethics consultation-emphasising both the process and outcome-created valuable moral spaces, promoting thoughtful and ethical responses to dilemmas in patient care. Future assessments should incorporate patient and family/surrogate perspectives and explore the domain of education as an additional quality measure.

Barriers and Facilitators to Obtaining Eyeglasses for Vulnerable Patients in a Michigan Free Clinic.

SIGNIFICANCE: Uncorrected refractive error is the main cause of visual impairment globally. Understanding barriers and facilitators underserved individuals face in obtaining eyeglasses will help address high rates of uncorrected refractive error. PURPOSE: The purpose of this study was to understand the barriers and facilitators to obtaining eyeglasses among low-income patients in Michigan. METHODS: Participants older than 18 years with hyperopia, myopia, or presbyopia and without active eye disease, severe mental illness, or cognitive impairment at Hope Clinic, Ypsilanti, Michigan, were included in this study. The participants answered a sociodemographic survey and underwent autorefraction and an interview. Interviews were audiorecorded, transcribed, and analyzed by two investigators. RESULTS: Interviews were completed by 43 participants, and 30 participants' interviews were analyzed. The mean ± standard deviation age of 30 participants was 55 ± 12 years, 70% were female, 57% were African American, 40% had high school diploma or less, 57% earned less than U.S. $25,000 per year, 93% had worn glasses previously, and 87% had some medical insurance. Uncorrected visual acuity was logMAR 0.73 ± 0.61; best-corrected visual acuity was logMAR 0.16 ± 0.21. Thematic saturation was reached after 25 transcripts. Top barriers to using eyeglasses were cost (312 mentions, 29 participants), negative experiences with eyeglasses (263, 29), and limited access to eye care (175, 27). Top facilitators were positive experiences with glasses (230, 29), easy access to eyeglasses (143, 27), and availability of transportation (65, 27). Most participants (97%, 29) reported being negatively impacted by uncorrected refractive error. Most (97%, 29) were skeptical about obtaining eyeglasses online because of possible prescription problems. CONCLUSIONS: Key barriers to correcting uncorrected refractive error in our community span across multiple health domains but are predominately rooted in external factors such as cost and access to vision care. Online eyeglasses may address access issues, but many participants were uncomfortable or unable to obtain glasses online.

Growth Arrest-Specific 6 (GAS6) Promotes Prostate Cancer Survival by G1 Arrest/S Phase Delay and Inhibition of Apoptosis During Chemotherapy in Bone Marrow.

Prostate cancer (PCa) is known to develop resistance to chemotherapy. Growth arrest-specific 6 (GAS6), plays a role in tumor progression by regulating growth in many cancers. Here, we explored how GAS6 regulates the cell cycle and apoptosis of PCa cells in response to chemotherapy. We found that GAS6 is sufficient to significantly increase the fraction of cells in G1 and the duration of phase in PCa cells. Importantly, the effect of GAS6 on G1 is potentiated during docetaxel chemotherapy. GAS6 altered the levels of several key cell cycle regulators, including the downregulation of Cyclin B1 (G2 /M phase), CDC25A, Cyclin E1, and CDK2 (S phase entry), while the upregulation of cell cycle inhibitors p27 and p21, Cyclin D1, and CDK4. Importantly, these changes became further accentuated during docetaxel treatment in the presence of GAS6. Moreover, GAS6 alters the apoptotic response of PCa cells during docetaxel chemotherapy. Docetaxel induced PCa cell apoptosis is efficiently suppressed in PCa cell culture in the presence of GAS6 or GAS6 secreted from co-cultured osteoblasts. Similarly, the GAS6-expressing bone environment protects PCa cells from apoptosis within primary tumors in vivo studies. Docetaxel induced significant levels of Caspase-3 and PARP cleavage in PCa cells, while GAS6 protected PCa cells from docetaxel-induced apoptotic signaling. Together, these data suggest that GAS6, expressed by osteoblasts in the bone marrow, plays a significant role in the regulation of PCa cell survival during chemotherapy, which will have important implications for targeting metastatic disease. J. Cell. Biochem. 117: 2815-2824, 2016. © 2016 Wiley Periodicals, Inc.

An evidenced-based diagnostic tool for superior semicircular canal dehiscence syndrome.

Purpose: To construct a symptoms-based prediction tool to assess the likelihood of superior canal dehiscence (SSCD) on high-resolution CT. Materials and methods: Mathematical modeling was employed to predict radiologic evidence of SSCD at a tertiary neurotology referral center. Results: A total of 168 patients were included, of which 118 had imaging-confirmed SSCD. On univariate analysis significant predictors of SSCD presence were: sound/pressure-induced vertigo (p = 0.006), disequilibrium (p = 0.008), hyperacusis (p = 0.008), and autophony (p = 0.034). Multivariate analysis enabled a 14-point symptom-weighted tool to be developed, wherein a score of ≥6 raised the suspicion of SSCD (≥70% likelihood of being present), R2 = 0.853. Conclusions: The likelihood of SSCD on CT scan can be determined with a high degree of certainty based on symptoms recorded at presentation. Using the evidenced-based diagnostic tool validated herein, a score ≥6 with any symptom combination justifies ordering a CT scan.

Surgical Fire in the United States: 2000-2020.

BACKGROUND: Despite fire prevention protocols and perioperative staff training, surgical fires continue to cause patient harm, disability, and death. METHODS: We identified surgical fires that were reported to the Food and Drug Administration's Manufacturer and User Facility Device Experience database between 2000 and 2020 that resulted in patient or surgical personnel harm. Quantitative and descriptive content analyses were performed on free-text responses to identify contributing factors of surgical fire patient and personnel harm events. RESULTS: We identified 565 surgical fire events resulting in patient or surgical personnel harm over a 20-year study period (median 25 events/year; range, 8-53). Surgical fires were significantly more likely to occur during upper aerodigestive tract (unadjusted odds ratio 15.96; 95% confidence interval, 11.93-21.34) and head and neck (unadjusted odds ratio 5.47; confidence interval 4.14-7.22) procedures compared with abdomen and pelvis procedures. Upper aerodigestive tract and head and neck procedures had the highest incidence of life-threatening injury (41% and 21%, respectively). An electrosurgical device was the ignition source in 82% of events. Content analysis revealed 7 common categories identified as root causes of surgical fires: preparation of surgical site (n = 55, 29%); device malfunction (n = 51, 26%), surgical accident (n = 47, 24%), medical judgement (n = 44 reports, 23%), equipment care and handling (n = 18, 9%), patient factors (n = 10, 5%), and communication (n = 3, 2%). CONCLUSION: Surgical fires resulting in harm to patient and surgical personnel continue to occur. The common themes identified in this study will prepare and empower surgeons and surgical personnel to prevent surgical fires in the future.

Neurotization of the radial forearm free flap improves swallowing outcomes in hemiglossectomy defects.

BACKGROUND: We examined the effect of free tissue neurotization on speech and swallowing outcomes for patients undergoing reconstruction of hemiglossectomy defects with a radial forearm free flap (RFFF). METHODS: A retrospective study was performed in patients with oral cavity squamous cell carcinoma undergoing a hemiglossectomy and reconstruction with a RFFF. Functional outcomes including nutritional mode, range of liquids and solids, and speech understandability were analyzed 1-year post-treatment. RESULTS: Eighty-four patients were included in this analysis, 41 of whom had neurotized flaps (49%). No significant differences in demographic or clinical variables were seen between the neurotized and non-neurotized groups. On multivariate analysis controlling for BMI, flap area, and N-classification, patients with neurotized flaps were significantly more likely to have normal range of liquids and solids and less likely to have a G-tube. CONCLUSIONS: Neurotization of RFFF reconstructing hemiglossectomy defects results in decreased G-tube dependence and improved range of liquids and solids.

Surgical Management of Rhabdomyosarcoma of the Nasal Cavity and Paranasal Sinuses: Analysis of Operative Indications, Settings, and Outcomes.

Objectives The role of surgery in management of sinonasal rhabdomyosarcoma (SNRMS) has traditionally been limited, owing to anatomic and technological challenges and the established role of systemic therapy. Herein, we report our institutional experience with surgical management of SNRMS, with a particular focus on operative approaches, extent and outcomes. Design This study is a retrospective cohort study. Setting This study was conducted at a single-institution, academic center. Participants Patients of any age with histologically confirmed RMS of the nasal cavity, maxillary, ethmoid, frontal, or sphenoid sinus, nasolacrimal duct, or nasopharynx presenting between 1994 and 2020 were included in this study. Main Outcome Measures Demographics, tumor characteristics, operative settings, complications and recurrence, and survival outcomes were the primary outcomes of this study. Results Our study cohort comprised of 29 patients (mean [range] age: 27.0 [3.1-65.7], n = 12 [41%] female). Tumors of the nasal cavity ( n = 10, 35%) and ethmoid sinuses ( n = 10, 35%) and those with alveolar histology ( n = 21, 72%) predominated. Patients who had surgery as part of their treatment ( n = 13, 45%) had improved distant metastasis-free survival (DMFS) overall (hazard ratio [HR]: 0.32, 95% CI: 0.11, 0.98, p = 0 .05 ) as compared with those who did not have surgery. Surgical approaches included open ( n = 7), endoscopic ( n = 4), and combined ( n = 2). Eight of these 13 patients (62%) had an R0 resection. Additionally, surgical salvage of recurrent disease was employed in five patients (17%). Conclusion SNRMS is an aggressive malignancy with a high rate of recurrence and spread requiring a multidisciplinary approach for optimal outcomes. Our data supports an expanding role for surgery for SNRMS given its feasibility, tolerability, and potential to improve outcomes.

Gender Microaggressions During Virtual Residency Interviews and Impact on Ranking of Programs During the Residency Match.

Background: Microaggressions are one form of gender bias contributing to gender disparities and mistreatment, but their prevalence during virtual residency interviews has not been explored. Objective: To explore applicants' recall of experiencing gender microaggressions during virtual residency interviews and whether these experiences affected programs' rank position on applicants' rank lists. Methods: Fourth-year medical students at a single institution who participated in the 2021 Match were surveyed after submitting their rank lists. Students were surveyed categorically on (1) their recall of the frequency they experienced 17 gender microaggressions during interviews, and (2) how these affected reported ranking of programs on their rank lists. Results: Sixty-one percent (103 of 170) of eligible students responded to the survey. Seventy-two percent (36 of 50) of women experienced at least one microaggression compared to 30% (9 of 30) of men. The largest difference was in the experience of environmental microaggressions, which are demeaning cues communicated individually or institutionally, delivered visually, or that refer to climate (P<.001). Women experienced more microaggressions than men in nonsurgical (P=.003) and surgical specialties excluding obstetrics and gynecology (P=.009). When microaggressions were experienced at 1 to 2 programs, 36% of applicants (26 of 73) reported significantly lowering program ranking, compared to 5% (1 of 19) when microaggressions occurred at more than 5 programs (P=.038). Conclusions: Women applicants experience more microaggressions than men do during nonsurgical and male-dominated surgical specialty residency interviews. Respondents who recalled experiencing microaggressions at fewer programs were more likely to report significantly lowering the rank of those programs compared to those who experienced them at more programs.

Pediatric Interprofessional ICU Ethics Rounds: A Single-Center Study.

OBJECTIVES: We sought to examine whether sociodemographic differences, such as race and socioeconomic status, existed between patients in the PICU, pediatric cardiothoracic ICU (PCTU), and NICU who were identified as having ethical issues during interprofessional ethics rounds and all other patients admitted to these units and to characterize the primary ethical issues identified in this context. METHODS: We compared sociodemographic factors among patients admitted to a quaternary academic children's hospital between January 2017 and December 2018 who were identified as having ethical issues during PICU, PCTU, and NICU interprofessional ethics rounds (n = 122) with those of all other patients admitted to these units (n = 4971). χ2 tests or Fisher's exact tests, Mann-Whitney U tests, and a multivariable logistic regression analysis were performed. RESULTS: With bivariate analyses, we detected significant differences by race, insurance type, and ventilator dependence, but no significant differences between the 2 groups existed on the basis of sex, ethnicity, religion, primary language, age, or a socioeconomic status metric. After we adjusted for confounders using a multivariable logistic regression analysis, only patients who were ventilator dependent were at significantly higher odds (odds ratio = 5.78; confidence interval = 3.69-9.04; P < .001) of being identified as having ethical issues. Goals of care was the most frequent ethical issue (44%). CONCLUSIONS: Except for ventilator dependence, patients with ethical issues during PICU, PCTU, and NICU interprofessional ethics rounds are demographically similar to overall patients admitted in these units. Future research should be used to assess whether proactive rounds impact the timing of ethics consultation requests as well as to determine if interprofessional ethics rounds influence volume and acuity in formal ethics consultation practices.

Patient Perceptions of Trust in Trainees During Delivery of Surgical Care: A Thematic Analysis.

OBJECTIVE: Trust is an essential element of an effective physician-patient relationship. There is limited literature examining trust between trainees and patients in the surgical setting. The goal of this study was to investigate how otolaryngology patients perceive trust in trainees during delivery of surgical care. DESIGN: We extracted trainee-specific data from a larger, qualitative interview study examining trust in the surgeon-patient relationship. We then used realist thematic analysis to explore preoperative otolaryngology patients' perceptions of trust in trainees during delivery of surgical care. SETTING: Department of Otolaryngology-Head and Neck Surgery at Michigan Medicine in Ann Arbor, MI, a tertiary academic medical center. PARTICIPANTS: Using convenience sampling, adults 18 years or older scheduled to undergo elective otolaryngologic surgery between February and June 2019 were invited, and 12 agreed to participate in the study. RESULTS: All participants (n = 12) self-identified as White/Caucasian with a mean age of 60 years (range, 28-82). Participants were 50% (n = 6) female and 50% (n = 6) male. Thematic analysis of participants' perspectives about trust in trainees during delivery of surgical care revealed 3 themes. Trust in trainees is conditional based on (i) level of trainee involvement; (ii) trust in the attending surgeon; and, (iii) trust in the institution. CONCLUSION: Trust in trainees during delivery of surgical care is conditional on types of tasks trainees perform, bounded by trust in their attending surgeon, and positively influenced by institutional trust. Trainees and surgical educators must look to innovative methods to engender trust more efficiently in the clinic and immediate pre-operative setting. Such approaches can have a positive impact on patient outcomes, facilitate stronger trainee-attending interpersonal relationships, and empower surgeons to practice the professional values integral to surgical care.

Patient perceptions of trust formation in the surgeon-patient relationship: A thematic analysis.

OBJECTIVE: Trust is crucial to the success of any personal or professional relationship. Literature on trust in the surgeon-patient relationship has been largely explored through quantitative methodologies, primarily examining why trust may or may not exist. We aimed to qualitatively elucidate the mechanisms of how trust develops between otolaryngologists and their patients. METHODS: Patients were recruited by surgery scheduling staff following an outpatient visit where a decision had been made to proceed with surgery at a tertiary academic medical center. We used qualitative realist thematic analysis of phone interviews to explore participants' (n = 17) perceptions and conceptualization of trust formation within the surgeon-patient relationship. RESULTS: Thematic analysis revealed three themes regarding trust formation in the surgeon-patient relationship: 1) Trust Across Various Contexts; 2) Impact of Prior Knowledge; and 3) Interpersonal Connection during the Clinical Encounter. CONCLUSION: An interpersonal surgeon-patient connection is crucial to the formation of trust. Trust is also influenced by surgeon and institutional reputation and witnessed surgeon interactions with the healthcare team. PRACTICE IMPLICATIONS: Patients perceive trust in a surgeon as carrying unique importance. To optimize conditions for trust development in this context, surgical care paradigms should promote meaningful preoperative interpersonal surgeon-patient relationships and positive surgeon and institutional reputations.

Disparities and ethical considerations for children with tracheostomies during the COVID-19 pandemic.

The COVID-19 pandemic is exacerbating longstanding challenges facing children with tracheostomies and their families. Myriad ethical concerns arising in the long-term care of children with tracheostomies during the COVID-19 pandemic revolve around inadequate access to care, healthcare resources, and rehabilitation services. Marginalized communities such as those from Black and Hispanic origins face disproportionate chronic illness because of racial and other underlying disparities. In this paper, we describe how these disparities also present challenges to children who are technology-dependent, such as those with tracheostomies and discuss the emerging ethical discourse regarding healthcare and resource access for this population during the pandemic.

Experiential-Learning Opportunities Enhance Engagement in Pipeline Program: A Qualitative Study of the Doctors of Tomorrow Summer Internship Program.

PURPOSE: Doctors of Tomorrow (DoT) is a pipeline program between the University of Michigan Medical School and Cass Technical High School in Detroit where the overall mission is to encourage youth from communities that are underrepresented in medicine to pursue their interests in healthcare careers. Students have the opportunity to apply for a summer internship between 9th grade and 10th grade. There is limited literature on the effectiveness of experiential-learning opportunities in pipeline programs to support development of personal and professional skills. The purpose of this study was to examine the experiences of students participating in the DoT summer internship program in order to better understand how their engagement influenced personal and professional development. METHOD: An exploratory qualitative study was conducted using responses from 27 students who participated in the DoT summer internship program between 2014 and 2018. Students engaged in self-reflective practices prompted by weekly surveys. Data were analyzed through an inductive process by coding and thematic analysis. RESULTS: Four overarching themes were identified: (1) engagement in authentic experiential-learning opportunities; (2) development of professional skills; (3) self-reflection and actualization; and (4) real world barriers in experiential-learning. CONCLUSIONS: High school students engaged in a variety of different community internships and shared insights that illustrated depth and diversity of understanding health in their community. Their reflections illustrate the added value of experiential-education in pipeline programs.

Endogenous GAS6 and Mer receptor signaling regulate prostate cancer stem cells in bone marrow.

UNLABELLED: GAS6 and its receptors (Tryo 3, Axl, Mer or "TAM") are known to play a role in regulating tumor progression in a number of settings. Previously we have demonstrated that GAS6 signaling regulates invasion, proliferation, chemotherapy-induced apoptosis of prostate cancer (PCa) cells. We have also demonstrated that GAS6 secreted from osteoblasts in the bone marrow environment plays a critical role in establishing prostate tumor cell dormancy. Here we investigated the role that endogenous GAS6 and Mer receptor signaling plays in establishing prostate cancer stem cells in the bone marrow microenvironment.We first observed that high levels of endogenous GAS6 are expressed by disseminated tumor cells (DTCs) in the bone marrow, whereas relatively low levels of endogenous GAS6 are expressed in PCa tumors grown in a s.c. SETTING: Interestingly, elevated levels of endogenous GAS6 were identified in putative cancer stem cells (CSCs, CD133+/CD44+) compared to non-CSCs (CD133-/CD44-) isolated from PCa/osteoblast cocultures in vitro and in DTCs isolated from the bone marrow 24 hours after intracardiac injection. Moreover, we found that endogenous GAS6 expression is associated with Mer receptor expression in growth arrested (G1) PCa cells, which correlates with the increase of the CSC populations. Importantly, we found that overexpression of GAS6 activates phosphorylation of Mer receptor signaling and subsequent induction of the CSC phenotype in vitro and in vivo.Together these data suggest that endogenous GAS6 and Mer receptor signaling contribute to the establishment of PCa CSCs in the bone marrow microenvironment, which may have important implications for targeting metastatic disease.