Psychosocial outcomes of human papillomavirus (HPV)- and non-HPV-related head and neck cancers: A longitudinal study.

OBJECTIVES: Human papillomavirus (HPV) has prompted a need to further investigate how this new biomarker changes the head and neck cancer (HNC) psychosocial landscape. This study aimed to: (a) characterize the sociodemographic, psychological, and social profiles of patients with HPV-positive versus -negative squamous cell carcinoma of the head and neck; and (b) identify how HPV status contributes to anxiety and depression (primary outcome), quality of life (QoL), and sexuality needs. METHODS: We conducted a prospective longitudinal study of 146 patients newly diagnosed with oral, oropharyngeal, nasopharyngeal, and hypopharyngeal cancer. Seventy-nine patients were HPV-positive and 67 HPV-negative. Patients completed self-administered psychometric measures upon HNC and 3-month follow-up, and Structured Clinical Interviews for DSM Diagnoses. RESULTS: Patients with HPV-negative tumors generally presented with higher anxiety and depression and lower QoL immediately post-HNC diagnosis (<2 weeks) compared to HPV-positive cancers. A Major Depressive Disorder (MDD) immediately post-HNC diagnosis negatively affected patients' anxiety and depression and QoL levels upon diagnosis only when the cancer was HPV-positive. Immediately posttreatment, HPV status was not associated with outcomes. A previous history of suicidal ideation, and upon cancer diagnosis cigarette smoking, anxiety and depression, and feeling close to one's partner were instead explanatory. CONCLUSION: While patients with HPV-positive HNC generally present with initially lower psychological distress, their vulnerability immediately posttreatment indicates an equal need for support. Head and neck clinics may need to better address MDD, anxiety and depression, a prior history of suicidal ideation, health behavior change, and quality of relationships.

Longitudinal study indicating antecedent psychosocial vulnerability as predictor of anxiety disorders post-treatment in people with head and neck cancer.

OBJECTIVE: This study aimed to: (1) determine the contribution of pre-cancer psychosocial vulnerability as an independent predictor of anxiety disorder (AD) onset immediately post-treatment in patients diagnosed with a first occurrence of head and neck cancer (HNC), controlling for sociodemographics and medical variables; and (2) estimate prevalence of AD and identify trajectories from the moment of diagnosis to the immediate post-treatment (i.e., over a period of 3 months) in this population. METHODS: Two-hundred twenty-four consecutive patients (participation rate = 72%) newly diagnosed with a primary HNC were assessed with a structured clinical interview for a mental disorder, validated psychometric measures, and medical chart reviews. RESULTS: Twenty-five percent of patients presented a lifetime AD, 19.4% within 2 weeks of HNC diagnosis, and 16.6% immediately post-treatment; representing 26.7% of patients with AD at any timepoint from the moment of diagnosis to immediately post-treatment. Patients were more likely to present an AD immediately post-treatment when they: were diagnosed with advanced-stage cancer (OR = 3.40, p = 0.006), presented a upon cancer diagnosis AD (OR = 2.45, p = 0.008) and/or experienced childhood abuse (OR = 1.96, p = 0.03). CONCLUSIONS: Several AD trajectories may arise when patients are diagnosed with primary HNC. Health professionals should address AD and screen for risk factors (i.e., advanced stage cancer, AD upon cancer diagnosis, history of childhood abuse) as early as possible to assure optimal mental health care in this vulnerable population.

Immediate post-treatment supportive care needs of patients newly diagnosed with head and neck cancer.

OBJECTIVE: This study aimed at identifying supportive care needs of patients with head and neck cancer (HNC-P) immediately post-treatment, finding early predictors of unmet needs, and contrasting how immediate post-treatment needs differed from needs in longer-term survivorship. METHODS: Prospective longitudinal study of 223 consecutive adults (313 approached; 72% participation) newly diagnosed with a first occurrence of primary HNC. Patients completed the Supportive Care Needs Survey-Short Form (SCNS), the Structured Clinical Interview for DSM-IV, and other outcomes. Medical chart reviews were conducted. RESULTS: A total of 68% of patients (n = 145/223) completed the SCNS. The multiple linear regression indicated that when controlled for medical variables, patients presented higher levels of unmet needs when they presented with higher level of anxiety upon HNC diagnosis (p = 0.03), higher neuroticism (p = 0.03), and more stressful life events in the year pre-diagnosis (p = 0.01). Patients immediately post-treatment had a wider variety of unmet needs compared with those in extended survivorship, with psychological unmet needs most prevalent at both time points. Immediately post-treatment, patients needed more support regarding pain (p = 0.04) and worries about treatment results (p = 0.05), whereas patients in longer-term survivorship needed more support regarding anxiety (p = 0.02), changes in sexual relationships (p = 0.04), and fear of death and dying (p = 0.001). CONCLUSION: This study identifies areas needing further development to improve quality of care for HNC-P in the immediate post-treatment period, as well as early determinants of unmet needs. HNC clinics may want to routinely screen for anxiety, neuroticism, and burden from other life events, to pro-actively address needs upon treatment completion and alleviate disease burden.

Pendrin Mediates Bicarbonate Secretion and Enhances Cystic Fibrosis Transmembrane Conductance Regulator Function in Airway Surface Epithelia.

Bicarbonate facilitates mucin unpacking and bacterial killing; however, its transport mechanisms in the airways are not well understood. cAMP stimulates anion efflux through the cystic fibrosis (CF) transmembrane conductance regulator (CFTR; ABCC7) anion channel, and this is defective in CF. The anion exchanger pendrin (SLC26A4) also mediates HCO3- efflux and is upregulated by proinflammatory cytokines. Here, we examined pendrin and CFTR expression and their contributions to HCO3- secretion by human nasal and bronchial epithelia. In native tissue, both proteins were most abundant at the apical pole of ciliated surface cells with little expression in submucosal glands. In well-differentiated primary nasal and bronchial cell cultures, IL-4 dramatically increased pendrin mRNA levels and apical immunostaining. Exposure to low-Cl- apical solution caused intracellular alkalinization (ΔpHi) that was enhanced fourfold by IL-4 pretreatment. ΔpHi was unaffected by 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) or CFTR inhibitor CFTRinh-172, but was reduced by adenoviral shRNA targeting pendrin. Forskolin increased ΔpHi, and this stimulation was prevented by CFTRinh-172, implicating CFTR, yet forskolin only increased ΔpHi after pendrin expression had been induced by IL-4. The dependence of ΔpHi on pendrin suggests there is minimal electrical coupling between Cl- and HCO3- fluxes and that CFTR activation increases anion exchange-mediated HCO3- influx. Conversely, inducing pendrin expression increased forskolin-stimulated, CFTRinh-172-sensitive current by approximately twofold in epithelial and nonepithelial cells. We conclude that pendrin mediates most HCO3- secretion across airway surface epithelium during inflammation and enhances electrogenic Cl- secretion via CFTR, as described for other SLC26A transporters.

Mutation-specific downregulation of CFTR2 variants by gating potentiators.

Approximately 50% of cystic fibrosis (CF) patients are heterozygous with a rare mutation on at least one allele. Several mutants exhibit functional defects, correctable by gating potentiators. Long-term exposure (≥24 h) to the only available potentiator drug, VX-770, leads to the biochemical and functional downregulation of F508del-CFTR both in immortalized and primary human airway cells, and possibly other CF mutants, attenuating its beneficial effect. Based on these considerations, we wanted to determine the effect of chronic VX-770 exposure on the functional and biochemical expression of rare CF processing/gating mutants in human airway epithelia. Expression of CFTR2 mutants was monitored in the human bronchial epithelial cell line (CFBE41o-) and in patient-derived conditionally reprogrammed bronchial and nasal epithelia by short-circuit current measurements, cell surface ELISA and immunoblotting in the absence or presence of CFTR modulators. The VX-770 half-maximal effective (EC50) concentration for G551D-CFTR activation was ∼0.63 µM in human nasal epithelia, implying that comparable concentration is required in the lung to attain clinical benefit. Five of the twelve rare CFTR2 mutants were susceptible to ∼20-70% downregulation by chronic VX-770 exposure with an IC50 of ∼1-20 nM and to destabilization by other investigational potentiators, thereby diminishing the primary functional gain of CFTR modulators. Thus, chronic exposure to VX-770 and preclinical potentiators can destabilize CFTR2 mutants in human airway epithelial models in a mutation and compound specific manner. This highlights the importance of selecting potentiator drugs with minimal destabilizing effects on CF mutants, advocating a precision medicine approach.

Contribution of psychiatric diagnoses to extent of opioid prescription in the first year post-head and neck cancer diagnosis: A longitudinal study.

PURPOSE: The purpose of this study was to determine, within the first-year post-head and neck cancer (HNC) diagnosis, the contribution of past and upon HNC psychiatric diagnoses (ie, substance use disorder, major depressive disorder, and anxiety disorder) to the extent (ie, cumulated dose) of opioid prescription. METHODS: Prospective longitudinal study of 223 consecutive adults (on 313 approached; 72% participation) newly diagnosed (<2 weeks) with a first occurrence of primary HNC, including Structured Clinical Interviews for DSM-IV disorders, validated psychometric measures, and medical chart reviews. Opioid doses were translated into standardized morphine milligram equivalents (MME) using CDC guidelines. A model of variables was tested using multiple linear regression. RESULTS: Fifty-five percent (123/223) of patients received opioids at some point during the first 12 months post-HNC diagnosis, 37.7% (84/223) upon HNC diagnosis (pre-treatment), 40.8% (91/223) during treatments, and 31.4% (70/223) post-treatment. The multiple linear regression indicated that an AD (P = 0.04) upon HNC diagnosis in early stage contributes to cumulated MME dose in the first year post-HNC diagnosis. CONCLUSION: This study underlines how anxiety has important repercussions on the management of pain and illustrates the importance of screening for AD upon HNC diagnosis to allow for early prophylactic treatment and support.

Development and validation of the McGill body image concerns scale for use in head and neck oncology (MBIS-HNC): A mixed-methods approach.

OBJECTIVE: The aim of this study was to develop and validate a patient-reported outcome measure to evaluate body image concerns in head and neck cancer (HNC) patients. METHODS: Items were created using a combination of deductive (eg, US Food and Drug Administration Qualification of Clinical Outcome Assessments, literature review) and inductive approaches (eg, subject matter experts, HNC patients). Items were translated for use in both Canadian English and Canadian French using back-translation. A two-step empirical validation process using the Classical Test Theory (CTT) and Rasch Measurement Theory (RMT) was conducted with 224 and 258 HNC patients, respectively, having undergone disfiguring surgery within the past 3 years. RESULTS: Analyses suggest two subscales for MBIS-HNC: social discomfort (10 items) and negative self-image (11 items). The McGill Body Image Concerns Scale-Head and Neck Cancer (MBIS-HNC) is reliable with high internal consistency (0.98), high test-retest reliability over a two-week period (ICC = 0.88), moderate to high convergent validity (range r = 0.43-0.81), and divergent validity (range r = 0.12-0.15). RMT was used in addition to CTT. Disordered thresholds led to the modification of the number of response options, and items were deleted based on differential item functioning and high local dependency. Unidimensionality of both subscales and supporting a total score was confirmed. The measure was however characterized by the presence of an important floor effect, confirmed with poor targeting as demonstrated by the person-item threshold distribution. CONCLUSION: Evidence gathered from our theory-driven validation study using CTT and RMT provides practitioners and researchers with a useful and easy to use self-report measure.

Barriers to psychosocial oncology service utilization in patients newly diagnosed with head and neck cancer.

OBJECTIVES: While patients with head and neck cancer (HNC) are known to experience higher levels of anxiety and depression, they do not always use psychosocial oncology (PSO) services when available. This study aimed to investigate barriers to PSO service utilization in this patient population, with the goal of appropriately targeting outreach interventions. METHODS: A conceptual model based on the Behavioral Model of Health Services Use was tested in 84 patients newly diagnosed with a first occurrence of HNC followed longitudinally over 1 year, including variables collected through self-administered questionnaires, Structured Clinical Interviews for DSM (SCID-I), and medical chart reviews. RESULTS: Within the first-year post-diagnosis, 42.9% of HNC patients experienced clinical levels of psychological distress, with only 50% of these consulting PSO services (29% total). A logistic regression indicated that PSO utilization was increased when patients presented with advanced cancer (P = 0.04) and a SCID-I diagnosis of major depressive disorder, anxiety disorder, or substance use disorder (P = 0.02), while there was an inverse relationship with self-stigma of seeking help (P = 0.03); these variables together successfully predicted 76.3% of overall PSO utilization, including 90.6% of non-users. CONCLUSIONS: Future outreach interventions in patients with HNC could address stigma in an attempt to enhance PSO integration into routine clinical care.

A screening algorithm for early detection of major depressive disorder in head and neck cancer patients post-treatment: Longitudinal study.

OBJECTIVE: The primary purpose of this study was to identify predictors of Major Depressive Disorder in head and neck cancer (HNC) patients in the immediate post-treatment period (ie, at 3 months post-diagnosis), with a focus on previously unexamined historical and contextual factors. METHODS: Prospective longitudinal study of 223 consecutive adults (72% participation) newly diagnosed with a first occurrence of primary HNC, including validated psychometric measures, Structured Clinical Interviews for DSM Disorders, and medical chart reviews. RESULTS: The 3-month period prevalence of Major Depressive Disorder was 20.4%; with point prevalences of 6.8% upon HNC diagnosis, 14.2% at 3 months, and 22.6% lifetime. Patients most susceptible to developing Major Depressive Disorder in the immediate post-treatment period: were diagnosed with advanced-stage cancer rather than early-stage cancer (O.R. = 4.94, P = 0.04), received surgery only (O.R. = 8.73, P = 0.04), presented a lifetime history of Anxiety Disorder on SCID-I (O.R. = 6.62; P = 0.01), and indicated higher pre-treatment levels of anxiety on the HADS (O.R. = 0.45, P = 0.05). CONCLUSIONS: Our results outline the predominant role of anxiety upon diagnosis as a precursor to post-treatment Major Depressive Disorder, suggesting the need for identification and prophylactic treatment of anxiety upon diagnosis in head and neck cancer patients. Further investigation into pathways by which pre-treatment anxiety predisposes to post-treatment Major Depressive Disorder in this population is warranted.

Thyroid cancer patients receiving an interdisciplinary team-based care approach (ITCA-ThyCa) appear to display better outcomes: Program evaluation results indicating a need for further integrated care and support.

BACKGROUND: Thyroid cancer (ThyCa) is generally associated with a favorable prognosis and excellent surgical outcomes. Consequently, its treatment is medically focused and current guidelines recommend interdisciplinary care including access to a nurse for complex cases alone. To date, no studies have evaluated the need for and impact of an Interdisciplinary Team-based Care Approach (ITCA-ThyCa) for general thyroid cancer patients, including a dedicated nurse as part of a larger interdisciplinary team, as well as patient-reported outcomes, as is recommended worldwide in cancer care. Our aim was to evaluate such a program. METHODS: The ITCA-ThyCa was evaluated within a quasi-experimental design using the Centers for Disease Control Framework for Program Evaluation, including process and outcome measures. Patients eligible were adults with a biopsy indicating confirmed or highly suspicious ThyCa (TNM-Classification + Bethesda score of V/VI). The intervention group (IG) received ITCA-ThyCa and the comparison group (CG), usual care alone. RESULTS: In our sample comprised of 200 participants (122 IG; 78 CG), ITCA-ThyCa patients appeared to show significantly better outcomes than CG patients, namely, higher levels of overall well-being (P = .001) and fewer physical (P = .003) and practical (P = .003) issues and concerns. More satisfied with their overall care (P = .028), including care coordination (P = .049), they reported their health care provider as more approachable (P = .007), respectful (P = .005), and trustworthy (P = .077; trend) and were more likely to recommend their hospital (P = .02). Ninety-eight percent of IG patients recommended ITCA-ThyCa. CONCLUSION: Data from our program illustrates that hospital resources should not be allocated based on medical trajectory alone and challenges the idea that ThyCa is "straightforward." ThyCa patients seem to experience symptom distress at a level comparable to-or exceeding-that of general oncological patients despite their promising medical outcomes, indicating that better integrated care and support are in order.

Recovering function and surviving treatments are primary motivators for health behavior change in patients with head and neck cancer: Qualitative focus group study.

OBJECTIVE: Against medical advice, head and neck cancer (HNC) patients have been shown to continue to smoke and misuse alcohol post-diagnosis and treatment. This study aimed to better understand the barriers to and facilitators of health behavior change (HBC) in HNC patients. METHOD: We conducted nine focus groups following a standard protocol. Eligible patients were diagnosed less than three years previously with a primary HNC and selected using maximum variability sampling (gender, age, cancer stage, smoking, and alcohol misuse). Thematic analysis was conducted using NVivo 10 software. RESULTS: Participants were mostly men (79%), 65 years of age (SD = 10.1), and married/common-law (52%, n = 15). Mean time from diagnosis was 19 months (SD = 12.3, range = 5.0-44.5), and most had advanced cancer (65.5%, n = 19). Participants provided a larger than anticipated definition of health behaviors, encompassing both traditional (smoking, drinking, diet, exercise, UV protection) and HNC-related (e.g., dental hygiene, skin care, speech exercises, using a PEG, gaining weight). The main emerging theme was patient engagement, that is, being proactive in rehabilitation, informed by the medical team, optimistic, flexible, and seeking support when needed. Patients were primarily motivated to stay proactive and engage in positive health behaviors in order to return to normal life and reclaim function, rather than to prevent a cancer recurrence. Barriers to patient engagement included emotional aspects (e.g., anxiety, depression, trauma, demoralization), symptoms (e.g., fatigue, pain), lack of information about HBC, and healthcare providers' authoritarian approach in counseling on HBC. We found some commonalities in barriers and facilitators according to behavior type (i.e., smoking/drinking/UV protection vs. diet/exercise). SIGNIFICANCE OF RESULTS: This study underlines the key challenges in addressing health behaviors in head and neck oncology, including treatment-related functional impairments, symptom burden, and the disease's emotional toll. This delicate context requires health promotion strategies involving close rehabilitative support from a multidisciplinary team attentive to the many struggles of patients both during treatments and in the longer-term recovery period. Health promotion in HNC should be integrated into routine clinical care and target both traditional and HNC-related behaviors, emphasizing emotional and functional rehabilitation as key components.

Looking beyond disfigurement: the experience of patients with head and neck cancer.

Despite the frequent occurrence of head and neck cancer (HNC) disfigurement, little is known about its psychosocial impact on patients. This study aimed to understand the lived experience of disfigurement in HNC and explore what patients considered to be its influences. Fourteen disfigured HNC patients participated in a 45-to-120-minute in-depth, semistructured interview, which was analyzed qualitatively using interpretive phenomenology. A majority of participants (64 percent) were considered to be at an advanced cancer stage (stage III or stage IV). Patients' experiences revolved around the concept of a ruptured self-image (a discontinuity in sense of self). Forces triggering this ruptured self-image created a sense of "embodied angst", in which disfigurement served as a constant reminder of the patient's cancer and associated foundational malaise. Other influences fostered a sense of normalcy, balance, and acceptance. Participants oscillated between these two states as they grew to accept their disfigurement. This study's findings could guide supportive interventions aimed at helping patients face head and neck surgery.

Genetic Risk For Depression and Quality of Life in Patients With Head and Neck Cancer.

Importance: Although patients with head and neck cancer (HNC) have been shown to experience high distress, few longitudinal studies include a comprehensive evaluation of biopsychosocial factors affecting quality of life (QoL), including genetic risk for depression. Objective: To identify factors at the time of cancer diagnosis associated with QoL scores at 3 months after treatment in patients newly diagnosed with a first occurrence of HNC. Design, Setting, and Participants: This prospective longitudinal study of 1464 participants with a 3-month follow-up, including structured clinical interviews and self-administered measures was carried out at the Department of Otolaryngology Head and Neck Surgery at 2 tertiary care McGill University Affiliated Hospitals, McGill University Health Centre, and Jewish General Hospital. Eligible patients were adults newly diagnosed within 2 weeks with a primary first occurrence of HNC, had a Karnofsky Performance Scale score higher than 60, and an expected survival of more than 6 months. Two hundred and twenty-three patients (72%) consented to participate and completed the baseline questionnaire, and 71% completed the 3-month follow-up measures. Exposures: An a priori conceptual model including sociodemographics, medical variables, psychosocial risk factors, and a polygenic risk score for depression (PRS-D) was tested. Main outcomes and measures: The Functional Assessment of Cancer Therapy-Head and Neck measured QoL at baseline and at 3 months. Results: Participants were mostly men (68.7%), with a mean (range) age of 62.9 (31-92) years, 36.6% having a university degree, 35.6% living alone, and 71.4% diagnosed with advanced HNC with mostly cancers being of the oropharynx (42.2%), oral cavity (17%), and larynx (16.3%). QoL at 3 months after HNC diagnosis was associated with higher PRS-D (B = -4.71; 95% CI, -9.18 to -0.23), and a diagnosis of major depressive disorder within 2 weeks of an HNC diagnosis (B = -32.24; 95% CI, -51.47 to 13.02), lifetime suicidal ideation (B = -22.39; 95% CI, -36.14 to -8.65), living with someone (B = 12.48; 95% CI, 3.43-21.52), having smoked cigarettes in the past 30 days pre-HNC diagnosis (B = -15.50; 95% CI, -26.07 to -4.93), chemotherapy type (B = -11.13; 95% CI, -21.23 to -1.02), and total radiotherapy dose (Gy) (B = -0.008; 95% CI, -0.01 to -0.002). Conclusions and relevance: This study identified the predictive value of a genetic predisposition to depression on QoL and function immediately after oncologic treatments. These findings highlight the potential importance of genetic profiling pretreatment to identify those most susceptible to experience QoL and functional compromise. Depression is a clear area of public health concern and should be a central focus in the treatment of patients with HNC.

Genetic predisposition to depression and inflammation impacts symptom burden and survival in patients with head and neck cancer: A longitudinal study.

OBJECTIVE: The primary purpose of this study was to investigate the contribution of genetic predispositions to depression and inflammation, as measured through polygenic risk scores, on symptom burden (physical and psychological) in patients with head and neck cancer in the immediate post-treatment period (i.e., at three months post-diagnosis), as well as on 3-, 6-, 12-, 24- and 36-month survival. METHODS: Prospective longitudinal study of 223 adults (72 % participation) newly diagnosed with a first occurrence of primary head and neck cancer, paired with genetic data (Illumina PsychArray), validated psychometric measures, Structured Clinical Interviews for DSM Disorders (SCID-I), and medical chart reviews. RESULTS: Symptom burden at 3 months was predicted by (R2 adj. = 0.38, p < 0.001): a baseline SCID-I Anxiety Disorder (b = 1.69, B = 0.23, 95%CI = 0.43-2.94; p = 0.009), baseline levels of HADS anxiety (b = 0.20, B = 0.29, 95%CI = 0.07-0.34; p = 0.003), the polygenic risk score (PRS) for depression (b = 0.66, B = 0.18, 95%CI = 0.003-1.32; p = 0.049), and cumulated dose of radiotherapy (b = 0.002, B = 0.46, 95%CI = 0.001-0.003; p < 0.001). When controlling for factors known to be associated with cancer survival, patients with a higher PRS associated with depression and inflammation, respectively, presented higher risk of death within 36 months (b = 1.75, Exp(B) = 5.75, 95%CI = 1.55-21.27, p = 0.009 and b = 0.14, Exp(B) = 1.15, 95%CI = 1.01-1.30, p = 0.03). CONCLUSIONS: Our results outline three potential pathways of symptom burden in patients with head and neck cancer: a genetic predisposition towards depression; an initial anxiety disorder upon being diagnosed with cancer or high levels of anxiety upon diagnosis; and a dose-related response to radiotherapy. One may want to investigate early interventions in these areas to alleviate symptom burden in patients faced with a life-threatening disease, as well as consider targeting genetic predisposition towards depression and inflammation implicated in survival. The high prevalence of distress in patients with head and neck cancer is an opportunity to study genetic predispositions, which could potentially be broadly generalized to other cancers and diseases.

Conducting an Endoscopic Sinus Surgery Dissection Course via Telesimulation: An Initial Experience.

Objective: Medical education has been severely disrupted by the COVID-19 pandemic, with many in-person educational activities transitioned to distance learning. To overcome this challenge, we utilized telesimulation to conduct an endoscopic sinus surgery (ESS) dissection course. Our objectives were to evaluate the effectiveness and acceptability of telesimulation as an alternative to in-person dissection courses for resident training. Study Design: Cross-sectional study. Setting: Academic medical centers. Methods: The course, consisting of lectures and hands-on dissection, was conducted entirely over the Zoom platform. The participants were allocated outpatient clinic rooms at 2 hospitals, while the instructors supervised remotely. We utilized the camera systems in the clinics and 3-dimensional-printed sinus models for the dissection. Laptops with cameras were used to capture the endoscopic image and the dissector. We evaluated the effectiveness of telesimulation, the surgical skills of the participants, and the course by way of pre- and posttest and a questionnaire. Results: A total of 8 participants and 7 instructors participated in the study. Telesimulation was found to be effective in helping participants gain knowledge and skills in ESS. All participants improved on their pretest scores (31.5% vs 73.4%, P = .003) and felt more comfortable with ESS postcourse (1.9 vs 3.2, P = .008). Participants and instructors opined that telesimulation is an acceptable alternative to in-person dissection courses. Conclusion: Telesimulation is an effective, acceptable, and viable alternative to in-person dissection courses. It also has the advantage of overcoming temporal and geographic constraints to surgical training in residency.

Body Image Concerns in Patients With Head and Neck Cancer: A Longitudinal Study.

Objective: Head and neck cancer (HNC) treatments are known to significantly affect functionality and appearance, leading to an increased risk for body image disturbances. Yet, few longitudinal studies exist to examine body image in these patients. Based on a conceptual model, the current study aimed to determine, in patients newly diagnosed with HNC: (1) the prevalence, level, and course of body image concerns; (2) correlates of upon cancer diagnosis (pre-treatment) body image concerns; (3) predictors of immediate post-treatment body image concerns; and (4) association between body image concerns and levels of anxiety, depression, suicidal ideation, support (i.e., satisfaction with support from physician, social/family wellbeing, and unmet support needs), and alcohol and drug misuse. Methods: Two hundred and twenty-three (participation rate = 72%), newly diagnosed with a primary HNC were assessed using structured clinical interviews and psychometric measures at three, and 6 months after diagnosis. Primary outcome was 3-month, as it was most salient to body image disturbance. Multiple linear regression analyses were conducted on the potential body image predictors, based on the model. Results: Sixty-eight percent of patients with HNC (n = 148 of 218) presented some level of body image concerns. Body image concerns at baseline (i.e., upon cancer diagnosis, pre-treatment) and post-treatment were significantly related and significantly increased from pre- to post-treatment. Immediately post-treatment (i.e., at 3 month follow-up), 89% (n = 132 of 148) presented some level of body image concerns. Correlates of body image concerns in patients with HNC at baseline included: physical symptom burden, difficulties with communication and eating, coping with the cancer diagnosis using denial, suicidal ideation, and having had a past anxiety diagnosis. When controlling for sociodemographic and medical variables, body image concerns in patients with HNC in the immediate post-treatment were predicted by: baseline body image, physical symptom burden, and neuroticism. Conclusion: This longitudinal study helps identify patients more susceptible to experience body image disturbance following head and neck cancer. Clinicians ought to pay special attention to body image concerns upon cancer diagnosis, physical symptom burden, and neuroticism, and may want to target these factors in future preventive interventions.

Biopsychosocial Markers of Body Image Concerns in Patients with Head and Neck Cancer: A Prospective Longitudinal Study.

(1) Background: Patients and survivors of head and neck cancer (HNC) are at a high risk of developing body image concerns. Despite the prevalence of body image concerns in patients with HNC, there is a lack of longitudinal research exploring the wide array of its associated determinants. The current longitudinal study examined the determinants and longitudinal course of body image dissatisfaction in patients with HNC. (2) Methods: Patients participated in Structured Clinical Interviews and self-administered questionnaires at four time-points: (T1) upon cancer diagnosis, (T2) at 3 months post-diagnosis, (T3) at 6 months post-diagnosis, and (T4) at 12 months post-diagnosis. They also underwent a disfigurement rating on an objective scale. (3) Results: Two hundred and twenty-four patients participated in our study. Fourteen percent to twenty-eight percent of patients reported at least moderate body image concerns across time points, with the lowest rates at baseline and the highest at 3 months (T1). It was found that patients more predisposed to developing higher levels of body image concerns presented physical markers (i.e., advanced cancer stage, lower physical functioning, higher disfigurement), psychosocial markers (i.e., higher depression, higher anxiety, and higher levels of coping with denial), and health disparities (i.e., younger age, female sex, French language, and marital status, with divorced and widowers most affected). (4) Conclusions: The findings of this study highlight the multifaceted nature of body image concerns in patients with HNC and its biopsychosocial determinants. Clinicians should pay specific attention to these biopsychosocial markers in their clinics to predict high levels of body image concerns and tailor communication/refer for support accordingly.

Large pH oscillations promote host defense against human airways infection.

The airway mucosal microenvironment is crucial for host defense against inhaled pathogens but remains poorly understood. We report here that the airway surface normally undergoes surprisingly large excursions in pH during breathing that can reach pH 9.0 during inhalation, making it the most alkaline fluid in the body. Transient alkalinization requires luminal bicarbonate and membrane-bound carbonic anhydrase 12 (CA12) and is antimicrobial. Luminal bicarbonate concentration and CA12 expression are both reduced in cystic fibrosis (CF), and mucus accumulation both buffers the pH and obstructs airflow, further suppressing the oscillations and bacterial-killing efficacy. Defective pH oscillations may compromise airway host defense in other respiratory diseases and explain CF-like airway infections in people with CA12 mutations.

Apoptotic Blocks in Primary Non-Hodgkin B Cell Lymphomas Identified by BH3 Profiling.

To determine causes of apoptotic resistance, we analyzed 124 primary B cell NHL samples using BH3 profiling, a technique that measures the mitochondrial permeabilization upon exposure to synthetic BH3 peptides. Our cohort included samples from chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), high-grade B cell lymphoma with translocations in MYC and BCL2 (HGBL-DH), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL). While a large number of our samples displayed appropriate responses to apoptosis-inducing peptides, pro-apoptotic functional defects, implicating BAX, BAK, BIM or BID, were seen in 32.4% of high-grade NHLs (12/37) and in 3.4% of low-grade NHLs (3/87, p < 0.0001). The inhibition of single anti-apoptotic proteins induced apoptosis in only a few samples, however, the dual inhibition of BCL2 and MCL1 was effective in 83% of samples, indicating MCL1 was the most common cause of lack of response to the BCL2 inhibitor, venetoclax. We then profiled Toledo and OCI-Ly8 high-grade lymphoma cell lines to determine which drugs could reduce MCL1 expression and potentiate venetoclax responses. Doxorubicin and vincristine decreased levels of MCL1 and increased venetoclax-induced apoptosis (all p < 0.05). Overall, in primary NHLs expressing BCL2 that have no defects in pro-apoptotic signaling, a poor response to venetoclax is primarily due to the presence of MCL1, which may be overcome by combining venetoclax with doxorubicin and vincristine-based chemotherapy or with other anti-microtubule inhibitors.

Allosteric folding correction of F508del and rare CFTR mutants by elexacaftor-tezacaftor-ivacaftor (Trikafta) combination.

Based on its clinical benefits, Trikafta - the combination of folding correctors VX-661 (tezacaftor), VX-445 (elexacaftor), and the gating potentiator VX-770 (ivacaftor) - was FDA approved for treatment of patients with cystic fibrosis (CF) carrying deletion of phenylalanine at position 508 (F508del) of the CF transmembrane conductance regulator (CFTR) on at least 1 allele. Neither the mechanism of action of VX-445 nor the susceptibility of rare CF folding mutants to Trikafta are known. Here, we show that, in human bronchial epithelial cells, VX-445 synergistically restores F508del-CFTR processing in combination with type I or II correctors that target the nucleotide binding domain 1 (NBD1) membrane spanning domains (MSDs) interface and NBD2, respectively, consistent with a type III corrector mechanism. This inference was supported by the VX-445 binding to and unfolding suppression of the isolated F508del-NBD1 of CFTR. The VX-661 plus VX-445 treatment restored F508del-CFTR chloride channel function in the presence of VX-770 to approximately 62% of WT CFTR in homozygous nasal epithelia. Substantial rescue of rare misprocessing mutations (S13F, R31C, G85E, E92K, V520F, M1101K, and N1303K), confined to MSD1, MSD2, NBD1, and NBD2 of CFTR, was also observed in airway epithelia, suggesting an allosteric correction mechanism and the possible application of Trikafta for patients with rare misfolding mutants of CFTR.