Quality of Life Outcomes after Free Fibula Flap Reconstruction of Mandibular Defects: A Longitudinal Examination.

BACKGROUND: A comprehensive understanding of changes in health-related quality of life after head and neck cancer surgery is necessary for effective preoperative counseling. The goal of this study was to perform a longitudinal analysis of postoperative quality of life outcomes after fibula free flap (FFF) mandible reconstruction. METHODS: A retrospective review was performed for all patients who underwent oncologic mandible reconstruction with an FFF between 2000 and 2021. Completion of at least one postoperative FACE-Q questionnaire was necessary for inclusion. FACE-Q scores were divided into five time periods for analysis. Functional outcomes measured with speech language pathology (SLP) assessments and tracheostomy and gastrostomy tube status were analyzed at three time points. RESULTS: One hundred and nine patients were included. Of these, 68 patients also had at least one SLP assessment. All outcomes as measured by the various FACE-Q scales did not improve significantly from the immediate postoperative time point to the last evaluated time point (p > 0.05). SLP functional outcomes showed some deterioration over time, but these were not significant (p > 0.05). The percentage of patients who required a tracheostomy (18 to 2%, p = 0.002) or gastrostomy tube (25 to 11%, p = 0.035) decreased significantly from the immediate postoperative time point to the last evaluated time point. CONCLUSION: Subjective quality of life outcomes do not change significantly with time after oncologic FFF mandible reconstruction. Reconstructive surgeons can use these results to help patients establish appropriate and achievable quality of life goals after surgery. Further studies are warranted to elucidate the impact of specific relevant clinical variables on postoperative quality of life.

Hypoxia-Directed Treatment of Human Papillomavirus-Related Oropharyngeal Carcinoma.

PURPOSE: Standard curative-intent chemoradiotherapy for human papillomavirus (HPV)-related oropharyngeal carcinoma results in significant toxicity. Since hypoxic tumors are radioresistant, we posited that the aerobic state of a tumor could identify patients eligible for de-escalation of chemoradiotherapy while maintaining treatment efficacy. METHODS: We enrolled patients with HPV-related oropharyngeal carcinoma to receive de-escalated definitive chemoradiotherapy in a phase II study (ClinicalTrials.gov identifier: NCT03323463). Patients first underwent surgical removal of disease at their primary site, but not of gross disease in the neck. A baseline 18F-fluoromisonidazole positron emission tomography scan was used to measure tumor hypoxia and was repeated 1-2 weeks intratreatment. Patients with nonhypoxic tumors received 30 Gy (3 weeks) with chemotherapy, whereas those with hypoxic tumors received standard chemoradiotherapy to 70 Gy (7 weeks). The primary objective was achieving a 2-year locoregional control (LRC) of 95% with a 7% noninferiority margin. RESULTS: One hundred fifty-eight patients with T0-2/N1-N2c were enrolled, of which 152 patients were eligible for analyses. Of these, 128 patients met criteria for 30 Gy and 24 patients received 70 Gy. The 2-year LRC was 94.7% (95% CI, 89.8 to 97.7), meeting our primary objective. With a median follow-up time of 38.3 (range, 22.1-58.4) months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 100%, respectively, for the 30-Gy cohort. The 70-Gy cohort had similar 2-year PFS and OS rates at 96% and 96%, respectively. Acute grade 3-4 adverse events were more common in 70 Gy versus 30 Gy (58.3% v 32%; P = .02). Late grade 3-4 adverse events only occurred in the 70-Gy cohort, in which 4.5% complained of late dysphagia. CONCLUSION: Tumor hypoxia is a promising approach to direct dosing of curative-intent chemoradiotherapy for HPV-related carcinomas with preserved efficacy and substantially reduced toxicity that requires further investigation.

Clinical, functional, and patient-reported outcomes of radial forearm versus anterolateral thigh free tissue transfer for reconstruction of glossectomy defects.

BACKGROUND: There is a lack of literature of health-related quality of life endpoints for radial forearm (RF) versus anterolateral thigh (ALT) free flap reconstruction for glossectomy defects. Our goal was to perform a comprehensive evaluation of clinical, functional, and quality of life outcomes after glossectomy reconstruction using a RF or ALT flap. METHODS: A retrospective review was performed on patients who underwent glossectomy and immediate reconstruction with RF or ALT flaps between 2016 and 2021. Outcomes of interest included readmission and reoperation rates, functional assessments, tracheostomy and gastrostomy tube status, and FACE-Q Head and Neck Cancer scores. RESULTS: Seventy-eight patients consisting of 54 RF and 24 ALT free flaps were included. ALT patients had a larger median flap size (72 vs. 48 cm2 , p = 0.021) and underwent mandibulotomy (50% vs. 7.4%, p < 0.0001) and base of tongue resection (58.3% vs. 24.1%, p = 0.005) at higher rates. No significant differences were found with respect to other outcomes. CONCLUSION: The RF and ALT flaps are suitable for glossectomy reconstruction, with minimal differences seen in postoperative outcomes. Our study suggests that ALT can be used in patients with base of tongue and larger defect sizes, while providing similar functional and clinical outcomes to RF reconstruction.

Impact of the COVID-19 Pandemic on Cancer Patient Educators.

Patient education (PE) is vital in reducing anxiety, increasing satisfaction with treatment, helping with self-management, and creating a sense of control for cancer patients. Patients access much of their material from health care providers through in-person visits, patient libraries, and in-person classes. Due to reductions in in-person visits throughout the pandemic, we sought to understand how PE programs responded under varying levels of COVID-19 restrictions to meet the information needs of patients and families. A cross-sectional survey was distributed to members of the Cancer Patient Education Network (CPEN) and the Health Care Education Association (HCEA) via the respective listservs. The survey consisted of five sections that included closed and opened questions. Participants were asked questions to describe their PE programs and how their duties were affected during the pandemic. Forty-two CPEN members completed the survey (N = 42, 66%) with a 35% response rate and a 55% completion rate, and 19 HCEA members completed the survey (N = 19, 30%) with a 5% response rate and 16% completion rate. The majority of staff surveyed were not furloughed (N = 57/64, 89%). Just under half reported a change in daily PE program activities (N = 23/52, 44%) and most reported a change in developing PE materials (e.g., pamphlets) (N = 10/26, 63%), finding information for patients/families (N = 11/19, 58%), and delivering classes (N = 12/21, 57%). COVID-19 has ushered in a new era in the delivery of PE with the rapid deployment of digital cancer patient education. Results can inform future directions for the delivery of PE post-pandemic.

Occupational hand dermatitis secondary to methacrylates-The 'manual tray' sign.

A case report of a dentist presenting with allergic contact dermatitis to methacrylates present in dental bonding agent applied on the dorsum of a gloved hand. The patient presented with a localized dermatitis to the dorsum of the non-dominant hand which can be described as a 'manual tray sign'.

Gradient boosting approaches can outperform logistic regression for risk prediction in cutaneous allergy.

BACKGROUND: Contact allergy is a major clinical and public health challenge. It is important to identify individuals who are at risk and perform patch testing to identify relevant allergens. Predicting clinical risk on the basis of input parameters is common in clinical medicine and traditionally has been achieved with linear models. OBJECTIVES: We hypothesized that the risk of a clinically relevant positive patch test could be predicted according to clinical and demographic parameters. METHODS: We compared the predictive accuracy of logistic regression with more sophisticated machine learning approaches such as gradient boosting, in the prediction of patch testing results. RESULTS: We found that both logistic regression and more sophisticated machine learning approaches were able to predict the risk of positive patch tests. For certain predictions, including the overall risk of a clinically relevant positive patch test, gradient boosting approaches can outperform logistic regression. CONCLUSIONS: These findings suggest that complex nonlinear interactions between input variables are relevant in risk prediction. While a risk prediction model cannot replace the judgment of an experienced clinician, quantifying the risk of a clinically relevant positive patch test result has the potential to assist in decision making and to inform discussions with patients.

Perforin, COVID-19 and a possible pathogenic auto-inflammatory feedback loop.

During COVID-19 infection, reduced function of natural killer (NK) cells can lead to both compromised viral clearance and dysregulation of the immune response. Such dysregulation leads to overproduction of cytokines, a raised neutrophil/lymphocyte ratio and monocytosis. This in turn increases IL-6 expression, which promotes scar and thrombus formation. Excess IL-6 also leads to a further reduction in NK function through downregulation of perforin expression, therefore forming a pathogenic auto-inflammatory feedback loop. The perforin/granzyme system of cytotoxicity is the main mechanism through which NK cells and cytotoxic T lymphocytes eliminate virally infected host cells, as well as being central to their role in regulating immune responses to microbial infection. Here, we present epidemiological evidence suggesting an association between perforin expression and resistance to COVID-19. In addition, we outline the manner in which a pathogenic auto-inflammatory feedback loop could operate and the relationship of this loop to genes associated with severe COVID-19. Such an auto-inflammatory loop may be amenable to synergistic multimodal therapy.

Oncologic and functional outcomes following laryngectomy for locally advanced thyroid cancer.

BACKGROUND AND OBJECTIVES: Total laryngectomy in thyroid cancer is controversial. Functional and oncologic outcomes are needed to inform surgical indications in this population. METHODS: A retrospective cohort study was performed at a tertiary referral center from 1997 to 2018 to identify patients with a diagnosis of thyroid carcinoma who underwent total laryngectomy. Complications, survival outcomes, and functional outcomes were analyzed. RESULTS: Thirty patients met the inclusion criteria. The mean age was 62 years (range, 30-88 years) and the male-to-female ratio was 1:2.75. The most common diagnosis was well-differentiated thyroid cancer (53.3%), followed by poorly differentiated (30%) and anaplastic (16.7%). Total laryngectomy was performed with a 10% rate of Clavien-Dindo Grade III-V complications. The median overall survival was 40 months (range, 1-237). Five-year overall survival was 39.5% and disease-specific survival was 51.1%. Locoregional control was achieved in 80.0% of patients. Twelve months postoperatively, 100% of surviving patients were taking oral intake and 86.4% had a self-reported functional voice. CONCLUSION: Total laryngectomy for locally advanced thyroid cancer is safe and provides acceptable rates of locoregional control. While the risk of distant metastases remains high, advances in systemic therapy may justify aggressive local control strategies to improve the quality of life.

Harnessing co-operative immune augmentation by contact allergens to enhance the efficacy of viral vaccines.

Although the development of successful vaccines against coronaviruses may be achieved, for some individuals the immune response that they stimulate may prove to be insufficient for effective host defence. The principle that a relatively strong contact allergen will have an enhancing effect on sensitization compared with a less potent contact allergen if they are co-administered, may not, at first, appear relevant to this issue. However, this augmentation effect is thought to be due to the sharing of common or complementary pathways. Here, we briefly consider aspects of the shared and complementary pathways between skin sensitization induced by exposure to a contact allergen and the immune response to viruses, with particular reference to COVID-19. The relationship leads us to explore whether this principle, which we name here as "co-operative immune augmentation" may be extended to include viral vaccination. We consider evidence that even relatively weak contact allergens, used in vaccines for other purposes, can show enhanced sensitization, which is in keeping with a co-operative augmentation principle. Finally, we consider how the potent contact allergen diphenylcyclopropenone could be employed safely as an enhancer of vaccine responses.

Integrated expression analysis of muscle hypertrophy identifies Asb2 as a negative regulator of muscle mass.

The transforming growth factor-ß (TGF-ß) signaling network is a critical regulator of skeletal muscle mass and function and, thus, is an attractive therapeutic target for combating muscle disease, but the underlying mechanisms of action remain undetermined. We report that follistatin-based interventions (which modulate TGF-ß network activity) can promote muscle hypertrophy that ameliorates aging-associated muscle wasting. However, the muscles of old sarcopenic mice demonstrate reduced response to follistatin compared with healthy young-adult musculature. Quantitative proteomic and transcriptomic analyses of young-adult muscles identified a transcription/translation signature elicited by follistatin exposure, which included repression of ankyrin repeat and SOCS box protein 2 (Asb2). Increasing expression of ASB2 reduced muscle mass, thereby demonstrating that Asb2 is a TGF-ß network-responsive negative regulator of muscle mass. In contrast to young-adult muscles, sarcopenic muscles do not exhibit reduced ASB2 abundance with follistatin exposure. Moreover, preventing repression of ASB2 in young-adult muscles diminished follistatin-induced muscle hypertrophy. These findings provide insight into the program of transcription and translation events governing follistatin-mediated adaptation of skeletal muscle attributes and identify Asb2 as a regulator of muscle mass implicated in the potential mechanistic dysfunction between follistatin-mediated muscle growth in young and old muscles.