Fat Grafting the Male Face.

There are many developmental sexual dimorphisms of the human face, and thereby differences in aging based on sex. Sensitivity regarding the nature of the changes that are unique to the male face as well as understanding men's unique aesthetic goals will allow the skilled practitioner to tailor rejuvenating treatments accordingly. Fat grafting of the male face has not been extensively described but is an excellent tool for facial rejuvenation either as an adjunct or a stand-alone procedure. Each treatment area demands different techniques and special attention to avoid unintentional feminization.

Patient-reported outcomes and morbidity after head and neck reconstructions: An evaluation of fibular and scapular free flaps.

BACKGROUND: Fibular (FFF) and scapular free flaps (SFF) are versatile tissue transfers for head and neck reconstruction. However, their relative morbidity has been sparsely studied. The primary goal of this study was to evaluate the morbidity and patient-reported outcome measures of these two reconstructive options. MATERIALS AND METHODS: Case series of patients from 2017 to 2020 who underwent a FFF or SFF for head and neck ablation. Demographic and surgical outcome measures, such as Charlson Comorbidity Index (CCI), anesthetic time, donor site morbidity, and perioperative morbidity score (POMs) were extracted. Patients were contacted to complete the Decision Regret Scale (DRS), University of Washington Quality of Life (UW-QoL), Oral Health Impact-14, and limb specific functional outcome measures. Statistical analyses included a linear regression. RESULTS: In total, 97 FFF (mean age 58.5, 62.9% male) and 55 SFF (mean age 64.8, 63.6% male) were included. Total surgical time was higher in the SFF group (p < 0.05) and they had more comorbidities (p < 0.01). SFF patients had lower POM scores on post-operative day three (p < 0.05) while FFF patients scored better on the UW-QoL Physical Domain (p < 0.01). The DRS for both groups (FFF mean DRS 22.7, SFF mean DRS 19.2) was similar. When adjusted for patient morbidity, however, the SFF group had less decisional regret (p < 0.05). CONCLUSION: This is the largest comprehensive evaluation of patient-reported outcome measures for FFF and SFFs. SFFs required longer surgical times but had less early morbidity than FFFs. Patients who underwent either reconstructions reported mild decisional regret, proving these are generally well tolerated procedures.

Synchrony in head and neck surgery: Feasibility and outcomes of simultaneous scapular free flap reconstruction.

BACKGROUND: The scapula free flap is a versatile option in head and neck reconstruction but is less amenable to simultaneous harvest and ablation. METHODS: Retrospective series (2015-2021) of consecutive scapula flaps. Cases categorized as simultaneous versus sequential, compared for operative time, oncological and patient-reported outcomes. RESULTS: Seventy consecutive scapula free flaps were performed (n = 21 simultaneous, n = 49 sequential). Mandible reconstruction was performed in 51.0% and 61.9% of sequential and simultaneous cases, respectively; 49.0% and 38.1% addressed bony maxillary defects. Simultaneous surgery reduced operative time by 37.9% (151 min, p < 0.00001) and there were fewer tracheostomies performed (p < 0.005). Rates of positive margins and free flap compromise were equivalent (n = 1, 4.8% vs. n = 2, 4.1%). There was no difference in patient-reported outcomes. CONCLUSIONS: This series demonstrates feasibility, efficacy, and outcomes of bony scapula reconstruction of maxillofacial defects comparing simultaneous and sequential approaches. Benefits of the two-team approach are highlighted including decreased operative time.

Dyskeratosis Congenita and Squamous Cell Cancer of the Head and Neck: A Case Report and Systematic Review.

OBJECTIVES: Dyskeratosis congenita (DC) is a progressive congenital disorder that predisposes patients to squamous cell cancers (SCC) of the head and neck. We report a case of a patient who underwent primary osteocutaneous free flap for mandibular SCC followed by additional treatments for positive margins and discuss a systematic review on therapeutic management for this patient population. METHODS: Case report of a 39-year-old male with DC who underwent resection and reconstruction with a fibular free flap for mandible SCC, followed by revision surgery and adjuvant radiotherapy for positive margins. A systematic review was completed afterward with the following terms: "dyskeratosis congenita" AND "oral cancer" OR "head and neck" OR "otolaryngology" on Medline and Web of Science for articles between 1980 and 2021. In total, 12 articles were included that reported on DC and SCC in the head and neck. RESULTS: Of the case reports that were included in this review, half the patients had recurrence within 1 year of primary treatments. Only 2 patients did not require revision surgery, adjuvant, or salvage therapy. Half of patients that received radiation therapy had severe side effects. CONCLUSIONS: This is the largest review of DC and SCC in the head and neck. Based off our case report and review, these patients have aggressive disease that often requires multi-modality treatment. Consideration should be taken in regards to reports of side effects with radiation therapy.

Prospective cohort study of voice outcomes following secondary tracheoesophageal puncture in gastric pull-up reconstruction after total laryngopharyngoesophagectomy.

BACKGROUND: Gastric pull-up is a reconstructive option for circumferential defects after resection of advanced laryngopharyngeal malignancy. Voice loss is expected and vocal rehabilitation remains a challenge. Our study objectives were to investigate the feasibility of secondary tracheoesophageal puncture following gastric pull-up and to analyze voice outcomes. METHODS: This was a prospective cohort study of patients with advanced laryngopharyngeal malignancies who underwent gastric pull-up and secondary tracheoesophageal puncture between 1988 and 2017 at a tertiary-care academic institution. Objective acoustic measures included fundamental frequency and vocal intensity. Perceptual analysis was performed using voice recordings ("Rainbow Passage") randomly presented in a blinded fashion to four clinicians using the validated GRBAS scale. Speech intelligibility was assessed in a blinded fashion using a validated 7-point scale. Additionally, the Voice Handicap Index-10 was administered as a validated patient self-reporting tool. RESULTS: Ten patients (7 male, 3 female) were included, all of whom preferentially used tracheoesophageal puncture for communication. These patients had abnormal median fundamental frequency of 250 (interquartile range (IQR) 214-265) Hz and a limited median vocal intensity of 65.8 (IQR 64.1-68.3) dB. Perceptual analysis (GRBAS) revealed a median 'moderate' degree of impairment [grade 2 (IQR 2-3), roughness 2 (IQR 2-3), breathiness 3 (IQR 2-3), asthenia 2 (IQR 1-2), strain 2 (IQR 1-2)] as did median intelligibility scores [median 5 (IQR 4-7)]. Most patients self-reported an abnormal voice handicap-10 [median 26.5 (IQR 22.8-35.0)]. CONCLUSION: Secondary tracheoesophageal puncture is a safe and feasible option for voice rehabilitation after gastric pull-up. Although analyses demonstrated moderate subjective and objective impairment, tracheoesophageal puncture provided patients with a self-reported means of functional verbal communication and was their preferred method of communication.

Blocking brain-derived neurotrophic factor inhibits injury-induced hyperexcitability of hippocampal CA3 neurons.

Brain trauma can disrupt synaptic connections, and this in turn can prompt axons to sprout and form new connections. If these new axonal connections are aberrant, hyperexcitability can result. It has been shown that ablating tropomyosin-related kinase B (TrkB), a receptor for brain-derived neurotrophic factor (BDNF), can reduce axonal sprouting after hippocampal injury. However, it is unknown whether inhibiting BDNF-mediated axonal sprouting will reduce hyperexcitability. Given this, our purpose here was to determine whether pharmacologically blocking BDNF inhibits hyperexcitability after injury-induced axonal sprouting in the hippocampus. To induce injury, we made Schaffer collateral lesions in organotypic hippocampal slice cultures. As reported by others, we observed a 50% reduction in axonal sprouting in cultures treated with a BDNF blocker (TrkB-Fc) 14 days after injury. Furthermore, lesioned cultures treated with TrkB-Fc were less hyperexcitable than lesioned untreated cultures. Using electrophysiology, we observed a two-fold decrease in the number of CA3 neurons that showed bursting responses after lesion with TrkB-Fc treatment, whereas we found no change in intrinsic neuronal firing properties. Finally, evoked field excitatory postsynaptic potential recordings indicated an increase in network activity within area CA3 after lesion, which was prevented with chronic TrkB-Fc treatment. Taken together, our results demonstrate that blocking BDNF attenuates injury-induced hyperexcitability of hippocampal CA3 neurons. Axonal sprouting has been found in patients with post-traumatic epilepsy. Therefore, our data suggest that blocking the BDNF-TrkB signaling cascade shortly after injury may be a potential therapeutic target for the treatment of post-traumatic epilepsy.

Enhanced recruitment of endosomal Na+/H+ exchanger NHE6 into Dendritic spines of hippocampal pyramidal neurons during NMDA receptor-dependent long-term potentiation.

Postsynaptic endosomal trafficking has emerged as a principal regulatory mechanism of structural and functional plasticity of glutamatergic synapses. Recycling endosomes perform activity-dependent transport of AMPA receptors (AMPARs) and lipids to the postsynaptic membrane, activities that are known to contribute to long-term synaptic potentiation and hypothesized to subserve learning and memory processes in the brain. Recently, genetic defects in a widely expressed vesicular pH-regulating transporter, the Na(+)/H(+) exchanger NHE6 isoform, have been implicated in neurodevelopmental disorders including severe X-linked mental retardation and autism. However, little information is available regarding the cellular properties of this transporter in the CNS. Here, we show by quantitative light microscopy that the protein abundance of NHE6 is developmentally regulated in area CA1 of the mouse hippocampus. Within pyramidal neurons, NHE6 was found to localize to discrete puncta throughout the soma and neurites, with noticeable accumulation at dendritic spines and presynaptic terminals. Dual immunolabeling of dendritic spines revealed that NHE6 partially colocalizes with typical markers of early and recycling endosomes as well as with the AMPAR subunit GluA1. Significantly, NHE6-containing vesicles exhibited enhanced translocation to dendritic spine heads during NMDA receptor (NMDAR)-dependent long-term potentiation. These data suggest that NHE6 may play a unique, previously unrecognized, role at glutamatergic synapses that are important for learning and memory.

Mitochondrial dysfunction and Purkinje cell loss in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS).

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset neurological disease resulting from mutations in the SACS gene encoding sacsin, a 4,579-aa protein of unknown function. Originally identified as a founder disease in Québec, ARSACS is now recognized worldwide. Prominent features include pyramidal spasticity and cerebellar ataxia, but the underlying pathology and pathophysiological mechanisms are unknown. We have generated an animal model for ARSACS, sacsin knockout mice, that display age-dependent neurodegeneration of cerebellar Purkinje cells. To explore the pathophysiological basis for this observation, we examined the cell biological properties of sacsin. We show that sacsin localizes to mitochondria in non-neuronal cells and primary neurons and that it interacts with dynamin-related protein 1, which participates in mitochondrial fission. Fibroblasts from ARSACS patients show a hyperfused mitochondrial network, consistent with defects in mitochondrial fission. Sacsin knockdown leads to an overly interconnected and functionally impaired mitochondrial network, and mitochondria accumulate in the soma and proximal dendrites of sacsin knockdown neurons. Disruption of mitochondrial transport into dendrites has been shown to lead to abnormal dendritic morphology, and we observe striking alterations in the organization of dendritic fields in the cerebellum of knockout mice that precedes Purkinje cell death. Our data identifies mitochondrial dysfunction/mislocalization as the likely cellular basis for ARSACS and indicates a role for sacsin in regulation of mitochondrial dynamics.