Reconstruction for Salvage Laryngectomy With Limited Pharyngectomy.

Importance: Closure technique for optimization of postoperative and functional outcomes following salvage laryngectomy remains an area of debate among head and neck surgeons. Objective: To investigate the association of salvage laryngectomy closure technique with early postoperative and functional outcomes. Design, Setting, and Participants: This retrospective cohort study included patients from 17 academic, tertiary care centers who underwent total laryngectomy with no or limited pharyngectomy after completing a course of definitive radiotherapy or chemoradiotherapy with curative intent between January 2011 and December 2016. Patients with defects not amenable to primary closure were excluded. Data were analyzed from February 14, 2021, to January 29, 2024. Exposures: Total laryngectomy with and without limited pharyngectomy, reconstructed by primary mucosal closure (PC), regional closure (RC), or free tissue transfer (FTT). Main Outcomes and Measures: Patients were stratified on the basis of the pharyngeal closure technique. Perioperative and long-term functional outcomes were evaluated with bivariate analyses. A multivariable regression model adjusted for historical risk factors for pharyngocutaneous fistula (PCF) was used to assess risk associated with closure technique. Relative risks (RRs) with 95% CIs were determined. Results: The study included 309 patients (256 [82.8%] male; mean age, 64.7 [range, 58.0-72.0] years). Defects were reconstructed as follows: FTT (161 patients [52.1%]), RC (64 [20.7%]), and PC (84 [27.2%]). A PCF was noted in 36 of 161 patients in the FTT group (22.4%), 25 of 64 in the RC group (39.1%), and 29 of 84 in the PC group (34.5%). On multivariable analysis, patients undergoing PC or RC had a higher risk of PCF compared with those undergoing FTT (PC: RR, 2.2 [95% CI, 1.1-4.4]; RC: RR, 2.5 [95% CI, 1.3-4.8]). Undergoing FTT was associated with a clinically meaningful reduction in risk of PCF (RR, 0.6; 95% CI, 0.4-0.9; number needed to treat, 7). Subgroup analysis comparing inset techniques for the RC group showed a higher risk of PCF associated with PC (RR, 1.8; 95% CI, 1.1-3.0) and predominately pectoralis myofascial flap with onlay technique (RR, 1.9; 95% CI, 1.2-3.2), but there was no association of pectoralis myocutaneous flap with cutaneous paddle interposition with PCF (RR, 1.2; 95% CI, 0.5-2.8) compared with FTT with cutaneous inset. There were no clinically significant differences in functional outcomes between the groups. Conclusion and Relevance: In this study of patients with limited pharyngeal defects, interpositional fasciocutaneous closure technique was associated with reduced risk of PCF in the salvage setting, which is most commonly achieved by FTT in academic practices. Closure technique was not associated with functional outcomes at 1 and 2 years postoperatively.

Wearable Biosensor Technology in Education: A Systematic Review.

Wearable Biosensor Technology (WBT) has emerged as a transformative tool in the educational system over the past decade. This systematic review encompasses a comprehensive analysis of WBT utilization in educational settings over a 10-year span (2012-2022), highlighting the evolution of this field to address challenges in education by integrating technology to solve specific educational challenges, such as enhancing student engagement, monitoring stress and cognitive load, improving learning experiences, and providing real-time feedback for both students and educators. By exploring these aspects, this review sheds light on the potential implications of WBT on the future of learning. A rigorous and systematic search of major academic databases, including Google Scholar and Scopus, was conducted in accordance with the PRISMA guidelines. Relevant studies were selected based on predefined inclusion and exclusion criteria. The articles selected were assessed for methodological quality and bias using established tools. The process of data extraction and synthesis followed a structured framework. Key findings include the shift from theoretical exploration to practical implementation, with EEG being the predominant measurement, aiming to explore mental states, physiological constructs, and teaching effectiveness. Wearable biosensors are significantly impacting the educational field, serving as an important resource for educators and a tool for students. Their application has the potential to transform and optimize academic practices through sensors that capture biometric data, enabling the implementation of metrics and models to understand the development and performance of students and professors in an academic environment, as well as to gain insights into the learning process.

Implementation of a Real-Time Brain-to-Brain Synchrony Estimation Algorithm for Neuroeducation Applications.

This study centers on creating a real-time algorithm to estimate brain-to-brain synchronization during social interactions, specifically in collaborative and competitive scenarios. This type of algorithm can provide useful information in the educational context, for instance, during teacher-student or student-student interactions. Positioned within the context of neuroeducation and hyperscanning, this research addresses the need for biomarkers as metrics for feedback, a missing element in current teaching methods. Implementing the bispectrum technique with multiprocessing functions in Python, the algorithm effectively processes electroencephalography signals and estimates brain-to-brain synchronization between pairs of subjects during (competitive and collaborative) activities that imply specific cognitive processes. Noteworthy differences, such as higher bispectrum values in collaborative tasks compared to competitive ones, emerge with reliability, showing a total of 33.75% of significant results validated through a statistical test. While acknowledging progress, this study identifies areas of opportunity, including embedded operations, wider testing, and improved result visualization. Beyond academia, the algorithm's utility extends to classrooms, industries, and any setting involving human interactions. Moreover, the presented algorithm is shared openly, to facilitate implementations by other researchers, and is easily adjustable to other electroencephalography devices. This research not only bridges a technological gap but also contributes insights into the importance of interactions in educational contexts.

Virtual surgical planning for mandibular reconstruction in an abbreviated admission pathway.

OBJECTIVES: Virtual Surgical Planning (VSP) creates individualized surgical plans for free flap reconstruction of mandibular defects. Prior studies indicate that VSP can offer cost benefits due to reduced operative time and length of stay (LOS). We assessed the impact of VSP in the context of a validated postoperative abbreviated LOS clinical pathway. METHODS: This study assessed patients undergoing VSP vs conventional fibular free flap reconstruction for mandibular defects (12/2015-10/2020) and their operative time, ischemia time, and LOS were evaluated. RESULTS: Forty-four patients underwent VSP reconstruction, while 52 patients underwent conventional reconstruction for mandibular defects. VSP was associated with significantly lower total operative time (6 h and 57 mins vs 7 h and 54 mins, p = 0.011), but not length of stay or ischemia time. Total OR time was significantly increased with increasing number of segments needed in both the VSP group (p = 0.002) and the conventional group (p = 0.015). CONCLUSION: Shorter operative times and LOS have been attributed to the use of VSP in free tissue transfers. It is argued that these reductions offset the added cost of VSP. Our study indicates that there is no cost benefit for VSP utilization due to a significantly reduced operative time with no impact on length of admission in an abbreviated admission clinical pathway following free tissue transfer.

Routine Contrasted Chest CT Accurately Identifies Anatomic Variations of the Proximal Subscapular System.

OBJECTIVE: The vascular anatomy of the proximal subscapular artery has been previously classified into 2 major types depending on the presence of a common subscapular trunk. The purpose of this study was to determine the utility, reliability, and cost of routine chest imaging to identify these anatomical variations. METHODS: Data were collected retrospectively at a tertiary medical center for patients who were undergoing CT chest for various indications between October 2019 and October 2020. Two independent and blinded readers interpreted CT chest with contrast of 52 patients for a total 104 sides. RESULTS: The proximal branching pattern of the subscapular system was identified to have a common trunk in 99 (95%) sides. The remaining five sides (5%) demonstrated two arterial pedicles; with one patient exhibiting the variant anatomy bilaterally. CONCLUSION: Preoperative CT chest with contrast can accurately identify anatomic variation of the subscapular vascular system. For complex reconstruction requiring a single anastomosis in the vessel depleted neck, preoperative imaging can assure selection of a type I vascular anatomy of the proximal subscapular system. Preoperative imaging with contrasted CT has value in assessing this anatomy when planning for chimeric flaps involving circumflex scapular and thoracodorsal arteries. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:684-687, 2024.

Correlating area deprivation index with initial stage at presentation and with follow up and recurrence within an advanced practice provider-led survivorship clinic.

INTRODUCTION: Living in disadvantaged neighborhoods has been shown to result in worse healthcare outcomes. The Area Deprivation Index (ADI) is a metric that ranks neighborhoods by socioeconomic disadvantage utilizing numerous factors including income, education, employment, and housing quality. METHODS: A retrospective review of all patients who underwent surveillance in an APP-led head and neck cancer survivorship clinic from Dec 2016 to Oct 2020 at an academic tertiary care center were included. Tumor characteristics, visit frequency, recurrence, number of missed appointments, loss of follow up, and ADI scores were collected. RESULTS: 543 patients were included in the study. A majority were male (69.9 %) and white race (84.9 %) with an average age of 64.6 years old. Average ADI national percentile score was 71.6(range: 17 to 100). ADI national percentile score was not predictive of tumor characteristics at initial presentation: lymphovascular invasion (p = 0.940; OR 1.0 [95 % CI: 0.9 to 1.1]), extranodal extension (p = 0.576; OR 1.0 [95 % CI: 0.9 to 1.2]), positive margins (p = 0.069; OR 0.9 [95 % CI: 0.9 to 1.0]). ADI national percentile score was not significantly correlated with loss to follow up (p = 0.153; OR 1.2 [95 % CI: 0.9 to 1.7] or cancer recurrence (p = 0.594; OR 1.0 [95 % CI: 0.9 to 1.1]). Missing one or more clinic visits was correlated with loss to follow up (p = 0.029; OR 13.1 [95 % CI: 1.3 to 131.7]. CONCLUSION: Living in a disadvantaged neighborhood did not correlate with negative tumor characteristics, loss to follow up, or recurrence within an APP-led survivorship head and neck cancer clinic.

Microvascular Free Flap Outcomes in Maxillectomy Defects from Invasive Fungal Sinusitis.

OBJECTIVES: Microvascular free tissue transfer is routinely used for reconstructing midface defects in patients with malignancy, however, studies regarding reconstructive outcomes in invasive fungal sinusitis (IFS) are lacking. We aim to describe outcomes of free flap reconstruction for IFS defects, determine the optimal time to perform reconstruction, and if anti-fungal medications or other risk factors of an immunocompromised patient population affect reconstructive outcomes. METHODS: Retrospective review of reconstruction for IFS (2010-2022). Age, BMI, hemoglobin A1c, number of surgical debridements, and interval from the last debridement to reconstruction were compared between patients with delayed wound healing versus those without. Predictor variables for delayed wound healing and the effect of time on free flap reconstruction were analyzed. RESULTS: Twenty-seven patients underwent free flap reconstruction for IFS. Three patients were immunocompromised from leukemia and 21 had diabetes mellitus (DM). Patients underwent an average of four surgical debridements for treatment of IFS. The interval from the last IFS debridement to flap reconstruction was 5.58 months (±5.5). Seven flaps (25.9%) had delayed wound healing. A shorter interval of less than 2 months between the last debridement for IFS and reconstructive free flap procedure was associated with delayed wound healing (Fisher Exact Test p = 0.0062). Other factors including DM, BMI, HgA1c, and bone reconstruction were not associated with delayed wound healing. CONCLUSION: Patients with maxillectomy defects from IFS can undergo microvascular-free flap reconstruction with good outcomes while on anti-fungal medication. Early reconstruction in the first 2 months after the last IFS debridement is associated with delayed wound healing. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1642-1647, 2024.

One hundred years of neurosciences in the arts and humanities, a bibliometric review.

BACKGROUND: Neuroscientific approaches have historically triggered changes in the conception of creativity and artistic experience, which can be revealed by noting the intersection of these fields of study in terms of variables such as global trends, methodologies, objects of study, or application of new technologies; however, these neuroscientific approaches are still often considered as disciplines detached from the arts and humanities. In this light, the question arises as to what evidence the history of neurotechnologies provides at the intersection of creativity and aesthetic experience. METHODS: We conducted a century-long bibliometric analysis of key parameters in multidisciplinary studies published in the Scopus database. Screening techniques based on the PRISMA method and advanced data analysis techniques were applied to 3612 documents metadata from the years 1922 to 2022. We made graphical representations of the results applying algorithmic and clusterization processes to keywords and authors relationships. RESULTS: From the analyses, we found a) a shift from a personality-focus quantitative analysis to a field-focus qualitative approach, considering topics such as art, perception, aesthetics and beauty; b) The locus of interest in fMRI-supported neuroanatomy has been shifting toward EEG technologies and models based on machine learning and deep learning in recent years; c) four main clusters were identified in the study approaches: humanistic, creative, neuroaesthetic and medical; d) the neuroaesthetics cluster is the most central and relevant, mediating between creativity and neuroscience; e) neuroaesthetics and neuroethics are two of the neologism that better characterizes the challenges that this convergence of studies will have in the next years. CONCLUSIONS: Through a longitudinal analysis, we evidenced the great influence that neuroscience is having on the thematic direction of the arts and humanities. The perspective presented shows how this field is being consolidated and helps to define it as a new opportunity of great potential for future researchers.

Loss of BAP1 Protein Expression by Immunohistochemistry in the Salivary Duct Carcinoma Component of an Intracapsular Carcinoma ex Pleomorphic Adenoma of the Parotid Gland.

BACKGROUND: BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is altered in a variety of neoplasms as well as in BAP1 tumor predisposition syndrome. BAP1 alterations are associated with aggressive behavior in some malignancies and may have treatment implications in future. We present the first documented case of loss of BAP1 protein expression by immunohistochemistry in the salivary duct carcinoma (SDC) component of an intracapsular carcinoma ex pleomorphic adenoma (CXPA) in the context of molecular loss of function of BAP1 in the neoplasm. METHODS: A woman of approximately 55 years of age presented with a deep parotid lobe mass, which was resected and found to be CXPA. BAP1 immunohistochemistry and next-generation sequencing was performed to further characterize the neoplasm. RESULTS: The neoplasm showed loss of BAP1 protein expression in the SDC component but retention in the residual pleomorphic adenoma (PA). Next-generation sequencing confirmed a BAP1 loss of function alteration in the neoplasm. CONCLUSION: This is the first documented case report of BAP1 protein expression loss in the SDC component of a CXPA. Future studies are needed to investigate the relevance of BAP1 alterations in SDC and CXPA, which may have prognostic and treatment implications.

Remote smart pill cap monitoring of post-surgical pain management in thyroid and parathyroid surgery.

BACKGROUND: With recent efforts to decrease opioid use following surgery, this study aims to answer: what pain regimen do patients follow at home? Is it controlling pain? METHODS: This is a prospective, pilot study of thyroid and parathyroid surgery patients. Patients were prescribed acetaminophen, ibuprofen, and tramadol dispensed in smart pill (Pillsy) bottles that record "events" corresponding to medication use. Patients received messages querying their current pain level. Patients were compared to historical controls. RESULTS: 26 patients were in the Pillsy group and 30 in the control group. In the Pillsy group, pain scores averaged 3.67 out of 10 in the first 24 h after surgery and decreased each day. Patients took an average of 6.45 doses of acetaminophen, 6.64 doses of ibuprofen, and 1.82 doses of tramadol in the first week. CONCLUSIONS: Pain scores are highest in the first 24 h after surgery and decrease thereafter. This acceptable level of pain can be achieved with non-opioid medications.

Brain-to-brain communication during musical improvisation: a performance case study.

Understanding and predicting others' actions in ecological settings is an important research goal in social neuroscience. Here, we deployed a mobile brain-body imaging (MoBI) methodology to analyze inter-brain communication between professional musicians during a live jazz performance. Specifically, bispectral analysis was conducted to assess the synchronization of scalp electroencephalographic (EEG) signals from three expert musicians during a three-part 45 minute jazz performance, during which a new musician joined every five minutes. The bispectrum was estimated for all musician dyads, electrode combinations, and five frequency bands. The results showed higher bispectrum in the beta and gamma frequency bands (13-50 Hz) when more musicians performed together, and when they played a musical phrase synchronously. Positive bispectrum amplitude changes were found approximately three seconds prior to the identified synchronized performance events suggesting preparatory cortical activity predictive of concerted behavioral action. Moreover, a higher amount of synchronized EEG activity, across electrode regions, was observed as more musicians performed, with inter-brain synchronization between the temporal, parietal, and occipital regions the most frequent. Increased synchrony between the musicians' brain activity reflects shared multi-sensory processing and movement intention in a musical improvisation task.

Evaluation of a Fast Test Based on Biometric Signals to Assess Mental Fatigue at the Workplace-A Pilot Study.

Non-pathological mental fatigue is a recurring, but undesirable condition among people in the fields of office work, industry, and education. This type of mental fatigue can often lead to negative outcomes, such as performance reduction and cognitive impairment in education; loss of focus and burnout syndrome in office work; and accidents leading to injuries or death in the transportation and manufacturing industries. Reliable mental fatigue assessment tools are promising in the improvement of performance, mental health and safety of students and workers, and at the same time, in the reduction of risks, accidents and the associated economic loss (e.g., medical fees and equipment reparations). The analysis of biometric (brain, cardiac, skin conductance) signals has proven to be effective in discerning different stages of mental fatigue; however, many of the reported studies in the literature involve the use of long fatigue-inducing tests and subject-specific models in their methodologies. Recent trends in the modeling of mental fatigue suggest the usage of non subject-specific (general) classifiers and a time reduction of calibration procedures and experimental setups. In this study, the evaluation of a fast and short-calibration mental fatigue assessment tool based on biometric signals and inter-subject modeling, using multiple linear regression, is presented. The proposed tool does not require fatigue-inducing tests, which allows fast setup and implementation. Electroencephalography, photopletismography, electrodermal activity, and skin temperature from 17 subjects were recorded, using an OpenBCI helmet and an Empatica E4 wristband. Correlations to self-reported mental fatigue levels (using the fatigue assessment scale) were calculated to find the best mental fatigue predictors. Three-class mental fatigue models were evaluated, and the best model obtained an accuracy of 88% using three features, ß/θ (C3), and the α/θ (O2 and C3) ratios, from one minute of electroencephalography measurements. The results from this pilot study show the feasibility and potential of short-calibration procedures and inter-subject classifiers in mental fatigue modeling, and will contribute to the use of wearable devices for the development of tools oriented to the well-being of workers and students, and also in daily living activities.

EEG-Based Tool for Prediction of University Students' Cognitive Performance in the Classroom.

This study presents a neuroengineering-based machine learning tool developed to predict students' performance under different learning modalities. Neuroengineering tools are used to predict the learning performance obtained through two different modalities: text and video. Electroencephalographic signals were recorded in the two groups during learning tasks, and performance was evaluated with tests. The results show the video group obtained a better performance than the text group. A correlation analysis was implemented to find the most relevant features to predict students' performance, and to design the machine learning tool. This analysis showed a negative correlation between students' performance and the (theta/alpha) ratio, and delta power, which are indicative of mental fatigue and drowsiness, respectively. These results indicate that users in a non-fatigued and well-rested state performed better during learning tasks. The designed tool obtained 85% precision at predicting learning performance, as well as correctly identifying the video group as the most efficient modality.

Functional outcome predictors following mandibular reconstruction with osteocutaneous fibula free flaps: correlating early postoperative videofluoroscopic swallow studies with long-term clinical results.

BACKGROUND: Advancements in the field of microvascular surgery and the widespread adoption of microvascular surgical techniques have made the use of osteocutaneous fibula free flaps the standard of care in the surgical management of segmental mandibular defects. Although the literature possesses abundant evidence to support the effectiveness of fibula free flaps as a reconstructive method, there are relatively few studies reporting on outcomes as objectively measured by videofluoroscopic swallowing studies (VFSS). The purpose of this study is to explore the potential correlation between early postoperative VFSS and the long-term swallowing outcomes in patients who underwent mandibular reconstruction with fibula free flaps. METHODS: We performed a retrospective chart review of 36 patients who underwent mandibular reconstruction with osteocutaneous fibular free flaps between 2009 and 2012. Demographics, clinical variables, VFSS data, and diet information were retrieved. Penetration and aspiration findings on VFSS, long-term oral feeding ability, and the need for gastrostomy tube were statistical endpoints correlated with postoperative clinical outcomes. RESULTS: Thirty-six patients were reviewed (15 females and 21 males) with a mean age of 54 years (7-81). Seventeen cases were treated for malignancy. The size of the bony defect ranged from 3 to 15 cm (mean = 9 cm). The cutaneous paddle, a surrogate for soft tissue defect, ranged from 10 to 125 cm2 (mean = 52 cm2). A gastrostomy tube was present in patients preoperatively (n = 8), and postoperatively (n = 14). Seventeen patients had neoadjuvant exposure to radiation. Postoperative VFSS showed penetration in 13 cases (36%) and aspiration in seven (19%). Overall, 29 patients (80.6%) achieved unrestricted diet, and this was statistically correlated with age (p = 0.037), radiation therapy (p = 0.002), and preoperative gastrostomy tube (p = 0.03). The presence of penetration or aspiration on VFSS was a strong predictor for long-term unrestricted oral diet (p < 0.001). CONCLUSION: Early postoperative VFSS is an excellent predictor for long-term swallowing outcomes in patients undergoing mandibular reconstruction with osteocutaneous fibula free flaps.

American Society of Anesthesiologists Class as Predictor for Perioperative Morbidity in Head and Neck Free Flaps.

OBJECTIVE: To evaluate outcomes of free flaps in low- versus high-risk American Society of Anesthesiologists (ASA) classes utilizing a standardized perioperative clinical pathway. STUDY DESIGN: Case series with chart review. SETTING: Single tertiary care academic institution. SUBJECTS AND METHODS: Data were collected from 301 patients who underwent 305 free flap reconstructions for head and neck defects from January 2012 to March 2016 by a single surgeon (M.M.). A standardized perioperative clinical pathway was utilized for all patients, aimed at abbreviating hospital stay and minimizing intensive care unit stay. Data included ASA classification, comorbidities, length of hospitalization, intensive care unit stay, 30-day mortality/readmission, discharge disposition, flap survival, and postoperative complications. Low-risk ASA classes were defined as 1 and 2 (n = 53) and high risk as 3 and 4 (n = 248). RESULTS: Total medical complication rates (P = .012) were mildly increased in the high-risk group, as a result of increased minor-not major-medical complication rates (P = .007). Discharge to a nursing or rehabilitation facility was found to be more common in the high-risk group (P = .024). All other outcomes were not statistically different between the cohorts. CONCLUSION: The ASA classification system is a validated tool in determining perioperative risk. We found that minor medical complications and discharge to a rehabilitation/nursing facility were increased in the high-risk ASA classes; otherwise, there were no statistical differences between the groups. These findings suggest that the ASA classification may be helpful for preoperative discharge planning and counseling but should not be used for patient selection or to assess candidacy for the procedure.

Clinical pathway for abbreviated postoperative hospital stay in free tissue transfer to the head and neck: Impact in resource utilization and surgical outcomes.

BACKGROUND: Assess the impact of a clinical pathway and progressive care unit (CPW/PCU) for patients undergoing head and neck free flap reconstruction with regard to patient outcomes and resource utilization. METHODS: Retrospective chart review of 270 patients at an academic tertiary-care center (2009-2014). Outcomes were compared among a control, CPW/PCU transition, and CPW/PCU groups. RESULTS: Compared to control, the CPW/PCU group had significantly reduced medical complications (21.1%-4.1%), intensive care unit length of stay (LOS, 5.02-0.2 days), hospital LOS (10.5-6.2 days), standardized total charges ($88 270-$58 661), and hospital costs ($41 365-$22 680). There were no observed differences in flap viability, surgical complications, reoperations, or readmissions. The CPW/PCU group achieved 100% home discharge. CONCLUSIONS: Our proposed CPW significantly improved patient outcomes and reduced resource utilization while maintaining flap outcomes. We propose a dynamic model for resource allocation that is easily reproducible in both academic and nonacademic settings.

Assessing a learning process with functional ANOVA estimators of EEG power spectral densities.

We propose to assess the process of learning a task using electroencephalographic (EEG) measurements. In particular, we quantify changes in brain activity associated to the progression of the learning experience through the functional analysis-of-variances (FANOVA) estimators of the EEG power spectral density (PSD). Such functional estimators provide a sense of the effect of training in the EEG dynamics. For that purpose, we implemented an experiment to monitor the process of learning to type using the Colemak keyboard layout during a twelve-lessons training. Hence, our aim is to identify statistically significant changes in PSD of various EEG rhythms at different stages and difficulty levels of the learning process. Those changes are taken into account only when a probabilistic measure of the cognitive state ensures the high engagement of the volunteer to the training. Based on this, a series of statistical tests are performed in order to determine the personalized frequencies and sensors at which changes in PSD occur, then the FANOVA estimates are computed and analyzed. Our experimental results showed a significant decrease in the power of [Formula: see text] and [Formula: see text] rhythms for ten volunteers during the learning process, and such decrease happens regardless of the difficulty of the lesson. These results are in agreement with previous reports of changes in PSD being associated to feature binding and memory encoding.

Head and Neck Reconstruction with Chimeric Anterolateral Thigh Free Flap: Indications, Outcomes, and Technical Considerations.

OBJECTIVE: Chimeric anterolateral thigh free flaps are composed of multiple skin paddles or muscular components that allow for the reconstruction of complex 3-dimensional defects. We present our experience with the technique and applications for various head and neck defects. STUDY DESIGN: Retrospective chart review. SETTING: Academic tertiary care center. SUBJECTS AND METHODS: Subjects include 24 consecutive patients undergoing reconstruction with a chimeric anterolateral thigh free flap by a single surgeon. Our algorithm for pharyngeal reconstruction with this technique is described. Data include demographics, indications, comorbidities, operative findings, and surgical outcomes. RESULTS: The most frequent defects were pharyngocutaneous (n = 12, 50%) and skull base (n = 6, 25%). The flap consisted of a double skin paddle in 11 cases (45.3%) and a skin paddle with an independent component of vastus lateralis muscle in 13 cases (54.7%). Revision surgery was required in 4 cases and was associated with malnutrition (P = .022). There were no total flap losses, but partial loss (distal skin paddle in all the cases) was observed in 3 patients and was related to severe congestive heart failure (P = .021) and malnutrition (P = .021). All except 1 patient who underwent pharyngeal reconstruction resumed oral diet and achieved alaryngeal speech. CONCLUSION: Chimeric anterolateral thigh free flaps represent an excellent option for reconstruction of complex head and neck defects. Modifications to the technique are proposed in patients at high risk of surgical complications.

Dual mTOR inhibitor MLN0128 suppresses Merkel cell carcinoma (MCC) xenograft tumor growth.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. Pathologic activation of PI3K/mTOR pathway and elevated expression of c-Myc are frequently detected in MCC. Yet, there is no targeted therapy presently available for this lethal disease. Recently, MLN0128, a second-generation dual TORC1/2 inhibitor is shown to have therapeutic efficacy in preclinical studies. MLN0128 is currently in clinical trials as a potential therapy for advanced cancers. Here we characterize the therapeutic efficacy of MLN0128 in the preclinical setting of MCC and delineate downstream targets of mTORC1/2 in MCC cellular systems. MLN0128 significantly attenuates xenograft MCC tumor growth independent of Merkel cell polyomavirus. Moreover, MLN0128 markedly diminishes MCC cell proliferation and induces apoptosis. Further investigations indicate that senescence does not contribute to MLN0128-mediated repression of xenograft MCC tumor growth. Finally, we also observe robust antitumor effects of MLN0128 when administered as a dual therapy with JQ1, a bromodomain protein BRD4 inhibitor. These results suggest dual blockade of PI3K/mTOR pathway and c-Myc axis is effective in the control of MCC tumor growth. Our results demonstrate that MLN0128 is potent as monotherapy or as a member of combination therapy with JQ1 for advanced MCC.

Disruption of BRD4 at H3K27Ac-enriched enhancer region correlates with decreased c-Myc expression in Merkel cell carcinoma.

Pathologic c-Myc expression is frequently detected in human cancers, including Merkel cell carcinoma (MCC), an aggressive skin cancer with no cure for metastatic disease. Bromodomain protein 4 (BRD4) regulates gene transcription by binding to acetylated histone H3 lysine 27 (H3K27Ac) on the chromatin. Super-enhancers of transcription are identified by enrichment of H3K27Ac. BET inhibitor JQ1 disrupts BRD4 association with super-enhancers, downregulates proto-oncogenes, such as c-Myc, and displays antitumor activity in preclinical animal models of human cancers. Here we show that an enhancer proximal to the c-Myc promoter is enriched in H3K27Ac and associated with high occupancy of BRD4, and coincides with a putative c-Myc super-enhancer in MCC cells. This observation is mirrored in tumors from MCC patients. Importantly, depleted BRD4 occupancy at the putative c-Myc super-enhancer region by JQ1 correlates with decreased c-Myc expression. Thus, our study provides initial evidence that super-enhancers regulate c-Myc expression in MCC.