Recent otolaryngology_oapdeposits items

Smad7-based biologic targeting epidermis and stroma promotes healing of diabetic wounds in mice and pigs

Thu, 9 Apr 2026 00:00:00 +0000

Diabetic wounds have limited effective therapies to restore tissue repair and resolve excessive inflammation. This study aimed to identify mechanisms of diabetic wound healing defects and test a therapeutic intervention using diabetic mouse and pig models. Here, we show that Smad7 transgene expression in mouse epidermis promotes wound healing in diabetic mice. To restrict the therapeutic effects of Smad7 on wounds, we develop a Smad7-based biologic (Tat-PYC-Smad7) that penetrates cells of the wound. Topical Tat-PYC-Smad7 treatment to diabetic pig and mouse wounds accelerates healing. Tat-PYC-Smad7-treated wounds exhibit reduced TGFβ/NFκB signaling, faster re-epithelialization, and better extracellular matrix remodeling compared to vehicle controls. Tat-PYC-Smad7 also attenuates neutrophil extracellular trap (NET) formation, potentially acting through reductions in MPO enzymatic activity and MPO nuclear entry, consequently reducing chromatin decondensation and the release of NET...

Should Antithrombotic Therapy Be Withheld Perioperatively for Cutaneous Facial Reconstructions?

Wed, 8 Apr 2026 00:00:00 +0000

Should Antithrombotic Therapy Be Withheld Perioperatively for Cutaneous Facial Reconstructions?

Distinct core thalamocortical pathways to central and dorsal primary auditory cortex

Thu, 15 Jan 2026 00:00:00 +0000

The cat primary auditory cortex (AI) is usually assumed to form one continuous functional region. However, the dorsal and central parts of the AI iso-frequency domain contain neurons that have distinct response properties to acoustic stimuli. In this study, we asked whether neurons projecting to dorsal versus central regions of AI originate in different parts of the medial geniculate body (MGB). Spike rate responses to variations in the sound level and frequency of pure tones were used to measure characteristic frequency (CF) and frequency resolution. These were mapped with high spatial density in order to place retrograde tracers into matching frequency regions of the central narrow-band region (cNB) and dorsal AI. Labeled neurons projecting to these two parts of AI were concentrated in the middle and rostral thirds of the MGB, respectively. There was little evidence that differences in dorsal and central AI function could be due to convergent input from cells outside the ventral...

The Contribution of Spike Threshold to Acoustic Feature Selectivity, Spike Information Content, and Information Throughput

Thu, 15 Jan 2026 00:00:00 +0000

Hypotheses of sensory coding range from the notion of nonlinear "feature detectors" to linear rate coding strategies. Here, we report that auditory neurons exhibit a novel trade-off in the relationship between sound selectivity and the information that can be communicated to a postsynaptic cell. Recordings from the cat inferior colliculus show that neurons with the lowest spike rates reliably signal the occurrence of stereotyped stimulus features, whereas those with high response rates exhibit lower selectivity. The highest information conveyed by individual action potentials comes from neurons with low spike rate and high selectivity. Surprisingly, spike information is inversely related to spike rates, following a trend similar to that of feature selectivity. Information per time interval, however, was proportional to measured spike rates. A neuronal model based on the spike threshold of the synaptic drive accurately accounts for this trade-off: higher thresholds enhance the...

Two thalamic pathways to primary auditory cortex

Thu, 15 Jan 2026 00:00:00 +0000

Neurons in the center of cat primary auditory cortex (AI) respond to a narrow range of sound frequencies and the preferred frequencies in local neuron clusters are closely aligned in this central narrow bandwidth region (cNB). Response preferences to other input parameters, such as sound intensity and binaural interaction, vary within cNB; however, the source of this variability is unknown. Here we examined whether input to the cNB could arise from multiple, anatomically independent subregions in the ventral nucleus of the medial geniculate body (MGBv). Retrograde tracers injected into cNB labeled discontinuous clusters of neurons in the superior (sMGBv) and inferior (iMGBv) halves of the MGBv. Most labeled neurons were in the sMGBv and their density was greater, iMGBv somata were significantly larger. These findings suggest that cNB projection neurons in superior and iMGBv have distinct anatomic and possibly physiologic organization.

Spatial Transcriptomic Landscape of Canine Oral Squamous Cell Carcinoma

Tue, 22 Jul 2025 00:00:00 +0000

Canine oral squamous cell carcinoma (COSCC) is the second most common oral tumor in dogs and the most relevant for comparative human trials as a spontaneous large animal model of disease. Historical genomic work has focused primarily on bulk sequencing. The present study describes the complete transcriptomic landscape of COSCC with spatial distinction between the surface tumor, deep invasive tumor, peritumoral dysplastic epithelium, and tumor microenvironment compared to matched normal oral samples. Each region demonstrated distinct molecular signatures. Genes related to epithelial growth factor (EGFR) and epithelial-mesenchymal transformation (EMT) were upregulated in both peritumoral dysplasia and surface cancer. Additionally, the KRAS gene set, KRT17, and SSP1 were enriched in cancer. We identified five genes that represent dysplastic lesion with high potential for malignant transformation (FZD4, GAS1, HACD2, NOG, and SLC39A6). Also, three genes, SFRP4, FZD1, and IL34 represented...

A practical and safer model of nitrogen mustard injury in cornea

Fri, 11 Jul 2025 00:00:00 +0000

PURPOSE: Sulfur mustard (SM) is an alkylating agent used in warfare and terrorism that inflicts devastating ocular injuries. Although the clinical symptoms are well described, the underlying mechanisms are not fully understood, hindering the development of effective treatments. One major roadblock is the lack of a suitable model due to the extremely hazardous nature of SM, which requires strict safety measures. As a safer and practical alternative, we report a novel model that uses mechlorethamine (nitrogen mustard) gel, an FDA-approved topical chemotherapeutic administered by patients at home. Here we demonstrate its suitability to induce mustard corneal injury in any laboratory. METHODS: Ex vivo porcine corneas were injured with mechlorethamine gel. Hematoxylin-eosin staining and immunohistochemistry were performed to evaluate histopathology of SM-like corneal injuries: epithelium thickness and stromal separation, keratocyte and inflammatory cell counts, and expression of inflammation...

Predictors of Donor‐Site Wound Complications Following Fibula Free Flap Reconstruction

Fri, 6 Jun 2025 00:00:00 +0000

Objective: The fibula free flap (FFF) remains the workhorse flap for head and neck defects necessitating osteocutaneous reconstruction. Although lower extremity angiography, ultrasound (US), and other vascular studies are routinely used for fibula assessment and patient selection, predictors of donor-site morbidity following harvest remain poorly understood. We sought to investigate the factors associated with FFF donor-site complications. Study Design: Retrospective analysis of patients at a tertiary care center. Setting: Tertiary care center. Methods: In total, 119 patients undergoing FFF reconstruction during the years 2012 to 2022 were included. Multivariable logistic regression was used to identify independent predictors of soft-tissue donor-site wound complications. Results: A total of 48 (40.3%) patients developed a donor-site wound complication with an average time to diagnosis of 24 days (±16) following surgery. In multivariable regression, history of alcohol use disorder...

Nanomedicine Approaches for Autophagy Modulation in Cancer Therapy

Wed, 7 May 2025 00:00:00 +0000

Cancer is a daunting global health problem with a steadily rising incidence. Despite the wide arsenal of current anticancer therapies, challenges such as drug resistance, tumor heterogeneity, poor targeting, and severe side effects often lead to suboptimal efficacy and poor patient outcomes, highlighting the need for innovative therapies. Autophagy modulation has emerged as an attractive approach to complement existing therapies. The dual role of autophagy in cancer promotion and suppression has inspired the development of new drugs and therapeutic strategies focusing on both inhibition and induction. Despite the promising results of current autophagy modulators in preclinical studies, challenges such as the lack of selectivity and potency, toxicity, poor pharmacokinetics, and inadequate tumor targeting continue to limit their successful clinical translation. Many of these challenges could be overcome using nanomedicine. This review explores recent advancements in nanomedicine...

Assessment of Patient Comprehension of Mohs Reconstruction Using Augmented Educational Materials in Preoperative Counselling

Wed, 7 May 2025 00:00:00 +0000

Assessment of Patient Comprehension of Mohs Reconstruction Using Augmented Educational Materials in Preoperative Counselling

Exploring a specific type of tissue-resident natural killer cell involved in the anti-tumor and immunotherapy response in human papillomavirus-positive head and neck squamous cell carcinoma using scRNA-seq

Mon, 21 Apr 2025 00:00:00 +0000

Background: Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is an increasingly common malignancy. We aimed to explore the immune heterogeneity of natural killer (NK) cells in HPV-positive HNSCC. Methods: Single-cell RNA-sequencing (scRNA-seq) and bulk RNA-sequencing datasets of HPV-positive HNSCC data were obtained from the Gene Expression Omnibus (GEO) database. "Seurat", "harmony", and "SingleR" were used to perform the scRNA-seq analysis. Subsequently, the "cellphonedb" package was used for the cell crosstalk analysis, and the "clusterProfiler" package was used for the hallmark pathway enrichment analysis. Finally, the "gene set variation analysis" ("GSVA") package was used for the immune cell infiltration, Tumor Immune Dysfunction and Exclusion (TIDE), and risk-score analyses. Results: A total of 30,562 cells were classified into 9 cell clusters that comprised 6 main cell types [i.e., T cells, natural killer T (NKT) cells, NK cells, B cells,...

Long read sequencing identifies complex structural variant landscape and recurrent TERT rearrangements in mucoepidermoid carcinoma

Thu, 17 Apr 2025 00:00:00 +0000

Mucoepidermoid Carcinoma (MEC) is a common salivary malignant neoplasm. Approximately 60 % of MECs harbor translocations between CRTC1 or CRTC3 and MAML2, which are thought to drive disease pathogenesis. However, the precise structural mechanism driving this rearrangement remains uncharacterized. Here, we performed multi-omic and long read genomic sequencing, discovering a chain of alterations that created the CRTC1::MAML2 fusion, but also an unexpected MAML2 to MYBL1 rearrangement, suggesting that MYBL1 may play a larger role in salivary gland cancers than previously recognized. Furthermore, we discovered and validated recurrent TERT rearrangements and amplifications in MEC models. 5/5 MEC cell lines and 36/39 (92 %) primary MEC tumors harbored a TERT rearrangement or copy number amplification. Custom sequencing of the TERT locus confirmed translocation breakpoints in 13/33 (39 %) MECs, while exome sequencing confirmed frequent TERT amplifications. Critically,...

Idiopathic Subglottic Stenosis in Non‐Caucasian Women

Fri, 11 Apr 2025 00:00:00 +0000

Objective: To characterize presentation, disease course, and treatment of idiopathic subglottic stenosis (iSGS) in non-Caucasian women and compare this cohort to the predominantly female, Caucasian patient cohorts identified in the literature. Study Design: Retrospective review. Results are compared to systematic review of demographics. Setting: Multiple California institutions from 2008 to 2021. Methods: Patients with intubation within 2 years of disease or who met exclusion criteria listed in prior publications were excluded. A systematic review of iSGS patient demographics was also completed for comparison. Results: Of 421 patients with iSGS, 58 self-identified as non-Caucasian women, with 50 ultimately included. Mean age of onset was 45.1 years old (95% confidence interval [CI], 41.5-48.8), and mean age at diagnosis was 47.2 years (95% CI, 43.6-50.7). Mean Charlson comorbidity index was 1.06 (n = 49, 95% CI, 0.69-1.44). At diagnosis, Cotton-Meyer severity scores (documented...

DNA immunotherapy for recurrent respiratory papillomatosis (RRP): phase 1/2 study assessing efficacy, safety, and immunogenicity of INO-3107

Wed, 2 Apr 2025 00:00:00 +0000

Recurrent respiratory papillomatosis (RRP) is a chronic airway disease caused by Human Papillomavirus (HPV). INO-3107, DNA immunotherapy designed to elicit T-cells against HPV-6 and HPV-11, was evaluated in a 52-week Phase 1/2 study for efficacy, safety, and immunogenicity (NCT04398433). Thirty-two eligible adults with HPV-6 and/or HPV-11 RRP, requiring ≥2 surgical interventions in the year preceding dosing were enrolled between October 2020 and November 2021 and administered 4 INO-3107 doses by intramuscular injection followed by electroporation. The primary endpoint was safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs). Secondary endpoints included surgical intervention frequency and change in RRP Severity Score (modified) post-INO-3107 and assessment of immune responses. 81% (26/32) of patients experienced surgery reduction following INO-3107 compared with the year prior to treatment. Blood assessments revealed HPV-6 and HPV-11 antigen-specific...

Poor nutrition status associated with low patient satisfaction six months into treatment for head and neck/esophageal cancer treatment: A prospective multicenter cohort study

Tue, 1 Apr 2025 00:00:00 +0000

BACKGROUND: Patient-reported outcome measures have been associated with survival in oncology patients. Altered intake and malnutrition are common symptoms for patients treated for head and neck cancer and esophageal cancer (HNC/EC). The purpose of this study was to examine the relationship between patient-reported satisfaction with medical care and nutrition status. METHODS: This prospective cohort study collected data from 11 international cancer care sites. RESULTS: One hundred and sixtythree adult patients (n = 115 HNC; n = 48 EC) completed a patient satisfaction questionnaire (the Canadian Health Care Evaluation Project Lite) and were included. HNC/EC patient global satisfaction with medical care was 88.3/100 ± 15.3 at baseline and remained high at 86.6/100 ± 16.8 by 6 months (100 max satisfaction score). Poor nutrition status, as defined by the Patient-Generated Subjective Global Assessment Short Form, was associated with lower patient satisfaction with overall medical care,...

Clinical Management Update of Oral Leukoplakia: A Review From the American Head and Neck Society Cancer Prevention Service

Mon, 20 Jan 2025 00:00:00 +0000

BACKGROUND: Oral potentially malignant disorders (OPMDs) occur in up to 4%-5% of the population, of which oral leukoplakia (OL) is the most common subtype. Predicting high-risk OL remains a challenge. Early diagnosis and effective treatment are thought to be of paramount importance to improve outcomes. METHODS: We searched PubMed and Clinicaltrials.gov data for updates in the clinical management of OL from 2015 to current. RESULTS: Recent publication of large cohorts of patients with OL aids in counseling patients regarding risk of malignant transformation. Management for OL includes surveillance, excision, and laser surgery, as well as local and systemic approaches to chemoprevention. Several new entities show promise regarding candidate biomarkers, chemoprevention agents, and diagnostic adjuncts, though all require further validation. CONCLUSION: This update serves to further inform clinical management of OL and provide impetus for future investigations. TRIAL REGISTRATION:...

Safety of a Novel Upper Esophageal Sphincter Balloon Dilator

Sun, 29 Dec 2024 00:00:00 +0000

OBJECTIVE: The shape of esophageal dilators has not changed in over 350 years. Clinical and animal research suggests that the upper esophageal sphincter (UES) is not round but approximates a kidney shape and that cylindrical dilators may be suboptimal. The Infinity UES Dilation System has been developed specifically for the anatomic configuration of the UES. This study evaluates the safety of the UES-specific Infinity Dilation System. METHODS: All patients undergoing dilation of the UES between January 1, 2022 and September 1, 2023 were included. Demographics, procedure indication, dilator type, minor adverse events, and major complications were abstracted. Minor adverse events, complications, and maximum dilation dimension (mm) were compared between groups. RESULTS: A total of 477 patients were included. Eight hundred and seventy-three total UES dilations were performed. The primary indications for UES dilation were cricopharyngeus muscle dysfunction (43%) and stenosis from radiation...

Pediatric Tracheostomy Emergency Readiness Assessment Tool: International Consensus Recommendations

Wed, 11 Dec 2024 00:00:00 +0000

OBJECTIVE: To achieve consensus on critical steps and create an assessment tool for actual and simulated pediatric tracheostomy emergencies that incorporates human and systems factors along with tracheostomy-specific steps. METHODS: A modified Delphi method was used. Using REDCap software, an instrument comprising 29 potential items was circulated to 171 tracheostomy and simulation experts. Consensus criteria were determined a priori with a goal of consolidating and ordering 15 to 25 final items. In the first round, items were rated as "keep" or "remove". In the second and third rounds, experts were asked to rate the importance of each item on a 9-point Likert scale. Items were refined in subsequent iterations based on analysis of results and respondents' comments. RESULTS: The response rates were 125/171 (73.1%) for the first round, 111/125 (88.8%) for the second round, and 109/125 (87.2%) for the third round. 133 comments were incorporated. Consensus (>60% participants scoring...

Worsening orbital roof “blow-in” fractures following traumatic brain injury: A report of two cases

Mon, 11 Nov 2024 00:00:00 +0000

Background: Orbital roof fractures are often the result of high-velocity collisions and are seen in 1-9% of patients with craniofacial trauma. Although the majority of orbital roof fractures are displaced superiorly, a subset results in inferior displacement of fracture fragments, posing a risk for muscle/nerve entrapment and possible blindness. Many of these patients have severe traumatic brain injury (TBI) and, in addition to orbital fractures, also have elevated intracranial pressure (ICP). Management of depressed orbital roof fractures in the setting of severe TBI with elevated ICP represents a management dilemma. Case Description: Two cases of severe TBI with associated downward displacement of orbital roof fractures were reviewed. Both cases exhibited elevated ICP correlated with the degree of orbital roof fracture depression. Surgical intervention involving elevation and repair of the fractures was undertaken when there was a significant risk of injury to the extraocular...

Anatomy-Specific Classification Model Using Label-Free FLIm to Aid Intraoperative Surgical Guidance of Head and Neck Cancer

Sat, 9 Nov 2024 00:00:00 +0000

Intraoperative identification of head and neck cancer tissue is essential to achieve complete tumor resection and mitigate tumor recurrence. Mesoscopic fluorescence lifetime imaging (FLIm) of intrinsic tissue fluorophores emission has demonstrated the potential to demarcate the extent of the tumor in patients undergoing surgical procedures of the oral cavity and the oropharynx. Here, we report FLIm-based classification methods using standard machine learning models that account for the diverse anatomical and biochemical composition across the head and neck anatomy to improve tumor region identification. Three anatomy-specific binary classification models were developed (i.e., "base of tongue," "palatine tonsil," and "oral tongue"). FLIm data from patients (N = 85) undergoing upper aerodigestive oncologic surgery were used to train and validate the classification models using a leave-one-patient-out cross-validation method. These models were evaluated for two classification tasks:...

Early Detection of Lymph Node Metastasis Using Primary Head and Neck Cancer Computed Tomography and Fluorescence Lifetime Imaging

Fri, 1 Nov 2024 00:00:00 +0000

Objectives: Early detection and accurate diagnosis of lymph node metastasis (LNM) in head and neck cancer (HNC) are crucial for enhancing patient prognosis and survival rates. Current imaging methods have limitations, necessitating new evaluation of new diagnostic techniques. This study investigates the potential of combining pre-operative CT and intra-operative fluorescence lifetime imaging (FLIm) to enhance LNM prediction in HNC using primary tumor signatures. Methods: CT and FLIm data were collected from 46 HNC patients. A total of 42 FLIm features and 924 CT radiomic features were extracted from the primary tumor site and fused. A support vector machine (SVM) model with a radial basis function kernel was trained to predict LNM. Hyperparameter tuning was conducted using 10-fold nested cross-validation. Prediction performance was evaluated using balanced accuracy (bACC) and the area under the ROC curve (AUC). Results: The model, leveraging combined CT and...

Is Postoperative Nasal Stenting Necessary After Primary Cleft Lip and Nose Repair?

Wed, 9 Oct 2024 00:00:00 +0000

The repair of an infant with cleft lip includes treatment of the nasal deformity using surgical repositioning of the nasal cartilages. In some cases, the nose is molded before surgery, termed nasoalveolar molding, and in others, postoperatively with nostril stents for a variable amount of time. This best practice evaluation fails to make a definitive evidence-based conclusion, yet the benefits of stenting seem to outweigh the risks.

Rates, Indications, and Speech Perception Outcomes of Revision Cochlear Implantations.

Wed, 9 Oct 2024 00:00:00 +0000

Revision cochlear implant (RCI) is a growing burden on cochlear implant programs. While reports on RCI rate are frequent, outcome measures are limited. The objectives of the current study were to: (1) evaluate RCI rate, (2) classify indications, (3) delineate the pre-RCI clinical course, and (4) measure surgical and speech perception outcomes, in a large cohort of patients implanted in a tertiary referral center between 1989-2018. Retrospective data review was performed and included patient demographics, medical records, and audiologic outcomes. Results indicated that RCI rate was 11.7% (172/1465), with a trend of increased RCI load over the years. The main indications for RCI were device-related failures (soft-45.4%, hard-23.8%), medical failure (14%), trauma (8.1%), and surgical failure (6.4%). Success rate was 98.8%. Children comprised 78% (134) of the cohort and were more likely than adults to undergo RCI. Most (70%) of the RCIs were performed within 10 years from primary...

The State of Craniomaxillofacial Trauma Care in Low‐ and Middle‐Income Countries: A Scoping Review

Mon, 9 Sep 2024 00:00:00 +0000

Objective: This scoping review aims to contribute a descriptive analysis of the craniomaxillofacial trauma (CMF trauma) literature in low- and middle-income countries (LMICs) to identify knowledge gaps, direct future research, and inform policy. Data Sources: PubMed/MEDLINE, Cochrane Review, EMBASE, ClinicalTrials.gov, and Google Scholar from January 1, 2012 to December 10, 2023. Review Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guided reporting, and the PRISMA flowchart documented database searches. Specific, predefined search terms and inclusion criteria were used for screening, and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was used for quality assessment. The search yielded 54 articles, with 13 meeting the inclusion criteria. Key findings were summarized and divided into 7 categories. Results: There were 10,420 patients (7739 [74.3%] male, 2681...

Cell derived matrices from bovine corneal endothelial cells as a model to study cellular dysfunction

Wed, 4 Sep 2024 00:00:00 +0000

PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is a progressive corneal disease that impacts the structure and stiffness of the Descemet's membrane (DM), the substratum for corneal endothelial cells (CECs). These structural alterations of the DM could contribute to the loss of the CECs resulting in corneal edema and blindness. Oxidative stress and transforming growth factor-β (TGF-β) pathways have been implicated in endothelial cell loss and endothelial to mesenchymal transition of CECs in FECD. Ascorbic acid (AA) is found at high concentrations in FECD and its impact on CEC survival has been investigated. However, how TGF-β and AA effect the composition and rigidity of the CEC's matrix remains unknown. METHODS: In this study, we investigated the effect of AA, TGF-β1 and TGF-β3 on the deposition, ultrastructure, stiffness, and composition of the extracellular matrix (ECM) secreted by primary bovine corneal endothelial cells (BCECs). RESULTS: Immunofluorescence and electron...

Inducible nitric oxide synthase (iNOS)-activated Cxcr2 signaling in myeloid cells promotes TGFβ-dependent squamous cell carcinoma lung metastasis

Sun, 1 Sep 2024 00:00:00 +0000

Transforming growth factor beta (TGFβ) activity is linked to metastasis in many cancer types, but whether TGFβ activity is necessary for squamous cell carcinoma (SCC) lung metastasis has not been studied. Here we used a lung metastatic SCC model derived from keratin 15 (K15). Kras^G12D.Smad4^-/- SCC and human SCC specimens to identify metastasis drivers and test therapeutic interventions. We demonstrated that a TGFβ receptor (TGFβR) inhibitor reduced lung metastasis in mouse SCC correlating with reduced CD11b⁺/Ly6G⁺ myeloid cells positive for inducible nitric oxide synthase (iNOS). Further, TGFβ activity and iNOS were higher in primary human oral SCCs with metastasis than SCCs without metastasis. Consistently, either depleting myeloid cells with anti-Gr1 antibody or inhibiting iNOS with L-N6-(1-iminoethyl)-l-lysine (L-NIL) reduced SCC lung metastasis. L-NIL treated tumor-bearing mice exhibited reductions in tumor-infiltrating myeloid cells...

Perspectives on the state of cleft lip and cleft palate patient care in Africa

Sat, 31 Aug 2024 00:00:00 +0000

PURPOSE OF REVIEW: Patients with cleft lip -palate (CLP) experience morbidity and social stigma, particularly in low-income and middle-income countries (LMICs) such as those of sub-Saharan Africa (SSA). Delays in treatment secondary either to lack of awareness, skills, equipment and consumables; poor health infrastructure, limited resources or a combination of them, has led to SSA having the highest rates of death and second highest rates of disability-adjusted life years in patients with CLP globally. Here we review current perspectives on the state of comprehensive cleft lip and palate repair in Africa. RECENT FINDINGS: To bridge gaps in government health services, nongovernmental organizations (NGOs) have emerged to provide care through short-term surgical interventions (STSIs). These groups can effect change through direct provision of care, whereas others strengthen internal system. However, sustainability is lacking as there continue to be barriers to achieving comprehensive...

Multi-kinase compensation rescues EGFR knockout in a cell line model of head and neck squamous cell carcinoma

Sat, 6 Jul 2024 00:00:00 +0000

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a debilitating disease with poor survival rates. While the epidermal growth factor receptor (EGFR)-targeting antibody Cetuximab is approved for treatment, responses are limited and the molecular mechanisms driving resistance remain incompletely understood. METHODS: To better understand how cells survive without EGFR activity, we developed an EGFR knockout derivative of the UM-SCC-92 cell line using CRISPR/Cas9 technology. We then characterized changes to the transcriptome with RNAseq and changes in response to kinase inhibitors with resazurin cell viability assays. Finally, we tested if inhibitors with activity in the EGFR knockout model also had synergistic activity in combination with EGFR inhibitors in either wild type UM-SCC-92 cells or a known Cetuximab-resistant model. RESULTS: Functional and molecular analysis showed that knockout cells had decreased cell proliferation, upregulation of FGFR1 expression, and an...

IL-22RA2 Is a SMAD7 Target Mediating the Alleviation of Dermatitis and Psoriatic Phenotypes in Mice

Sat, 8 Jun 2024 00:00:00 +0000

Long-term management of inflammatory skin diseases is challenging because of side effects from repeated use of systemic treatments or topical corticosteroids. This study sought to identify the mechanisms and developmental therapeutics for these diseases using genetic models and pharmacological approaches. We found that mice overexpressing SMAD7 in keratinocytes but not mice overexpressing the N-terminal domain of SMAD7 (i.e., N-SMAD7) were resistant to imiquimod-induced T helper 1/17- and T helper 2-type inflammation. We generated a Tat-PYC-SMAD7 (truncated SMAD7 protein encompassing C-terminal SMAD7 and PY motif fused with cell-penetrating Tat peptide). Topically applied Tat-PYC-SMAD7 to inflamed skin entered cells upon contact and attenuated imiquimod-, 2,4-dinitrofluorobenzene-, and tape-stripping-induced inflammation. RNA-sequencing analyses of mouse skin exposed to these insults showed that in addition to inhibiting TGFβ/NF-κB, SMAD7 blunted IL-22/signal transducer and activator...

Stratification of surgical margin distances by the millimeter on local recurrence in oral cavity cancer: A systematic review and meta‐analysis

Wed, 15 May 2024 00:00:00 +0000

There are limited data supporting the commonly suggested 5 mm margin cutoff as the optimum value in defining clear margins in oral cancer. A database search of Pubmed/Medline, Web of Science, and EBSCOhost was performed from inception to June 2022. A random-effects model was chosen for this meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed throughout this study. Seven studies met study criteria (2215 patients). The risk ratio was significantly higher for margins <5 mm when compared to those ≥5 mm (2.09 (95%CI: 1.53-2.86, I² = 0.47)). Subgroup analysis (I² = 0.15) of margin distances of 0.0-0.9, 1.0-1.9, 2.0-2.9, 3.0-3.9, and 4.0-4.9 mm calculated risk ratios for local recurrence of 2.96, 2.01, 2.17, 1.8, and 0.98, respectively. Margins between 4.0 and 4.9 mm had similar risk ratios for local recurrence compared to ≥5 mm, while margins <4.0 were significantly higher.

Portrait of a Surgeon: Artificial Intelligence Reflections

Sat, 27 Apr 2024 00:00:00 +0000

Text-to-image artificial intelligence (AI) programs are popular public-facing tools that generate novel images based on user prompts. Given that they are trained from Internet data, they may reflect societal biases, as has been shown for text-to-text large language model programs. We sought to investigate whether 3 common text-to-image AI systems recapitulated stereotypes held about surgeons and other health care professionals. All platforms queried were able to reproduce common aspects of the profession including attire, equipment, and background settings, but there were differences between programs most notably regarding visible race and gender diversity. Thus, historical stereotypes of surgeons may be reinforced by the public's use of text-to-image AI systems, particularly those without procedures to regulate generated output. As AI systems become more ubiquitous, understanding the implications of their use in health care and for health care-adjacent purposes is critical to...

International Society for Extracellular Vesicles and International Society for Cell and Gene Therapy statement on extracellular vesicles from mesenchymal stromal cells and other cells: considerations for potential therapeutic agents to suppress coronavirus disease-19

Mon, 8 Apr 2024 00:00:00 +0000

STATEMENT: The International Society for Cellular and Gene Therapies (ISCT) and the International Society for Extracellular Vesicles (ISEV) recognize the potential of extracellular vesicles (EVs, including exosomes) from mesenchymal stromal cells (MSCs) and possibly other cell sources as treatments for COVID-19. Research and trials in this area are encouraged. However, ISEV and ISCT do not currently endorse the use of EVs or exosomes for any purpose in COVID-19, including but not limited to reducing cytokine storm, exerting regenerative effects or delivering drugs, pending the generation of appropriate manufacturing and quality control provisions, pre-clinical safety and efficacy data, rational clinical trial design and proper regulatory oversight.

Computer assisted skull base surgery: a contemporary review

Mon, 19 Feb 2024 00:00:00 +0000

Skull base surgery has evolved significantly since Harvey Cushing's first descriptions in the early 1900s. Computer aided surgery (CAS) applications continue to expand; they include virtual surgical planning, augmented and virtual reality, 3D printing of models/cutting guides/implants, surgical navigation, and intraoperative imaging. The authors will review the current skull base CAS literature and propose a computer aided surgical workflow categorizing these applications into 3 phases: 1) Virtual planning, 2) Surgical execution, 3) Intraoperative verification.

Association of Social Determinants of Health with Time to Diagnosis and Treatment Outcomes in Idiopathic Subglottic Stenosis

Fri, 2 Feb 2024 00:00:00 +0000

OBJECTIVES: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients. METHODS: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical...

Commentary on Benjamin et al.'s “Assessing the Prevalence of Craniomaxillofacial Injuries Among Helmeted and Unhelmeted Electric Scooter Users”: A Call to Action for Logical Protection

Wed, 31 Jan 2024 00:00:00 +0000

Commentary on Benjamin et al.'s “Assessing the Prevalence of Craniomaxillofacial Injuries Among Helmeted and Unhelmeted Electric Scooter Users”: A Call to Action for Logical Protection

International Consensus Statement on Obstructive Sleep Apnea

Wed, 10 Jan 2024 00:00:00 +0000

BACKGROUND: Evaluation and interpretation of the literature on obstructive sleep apnea (OSA) allows for consolidation and determination of the key factors important for clinical management of the adult OSA patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International Consensus statement on Obstructive Sleep Apnea (ICS:OSA). METHODS: Using previously defined methodology, focal topics in OSA were assigned as literature review (LR), evidence-based review (EBR), or evidence-based review with recommendations (EBR-R) formats. Each topic incorporated the available and relevant evidence which was summarized and graded on study quality. Each topic and section underwent iterative review and the ICS:OSA was created and reviewed by all authors for consensus. RESULTS: The ICS:OSA addresses OSA syndrome definitions, pathophysiology, epidemiology, risk factors for disease, screening methods, diagnostic...

Revisiting laminin and extracellular matrix remodeling in metastatic squamous cell carcinoma: What have we learned after more than four decades of research?

Fri, 5 Jan 2024 00:00:00 +0000

Patients with squamous cell carcinoma (SCC) have significantly lower survival upon the development of distant metastases. The extracellular matrix (ECM) is a consistent yet dynamic influence on the metastatic capacity of SCCs. The ECM encompasses a milieu of structural proteins, signaling molecules, and enzymes. Just over 40 years ago, the fibrous ECM glycoprotein laminin was identified. Roughly four decades of research have revealed a pivotal role of laminins in metastasis. However, trends in ECM alterations in some cancers have been applied broadly to all metastatic diseases, despite evidence that these characteristics vary by tumor type. We will summarize how laminins influence the SCC metastatic process exclusively. Enhanced laminin protein deposition occurs at the invasive edge of SCC tumors, which correlates with elevated levels of laminin-binding β1 integrins on SCC cells, increased MMP-3 presence, worse prognosis, and lymphatic dissemination. Although these findings are...

Prognostic value of CD103+ tumor-infiltrating lymphocytes and programmed death ligand-1 (PD-L1) combined positive score in recurrent laryngeal squamous cell carcinoma

Fri, 8 Dec 2023 00:00:00 +0000

OBJECTIVES: In an evolving era of immunotherapeutic options for persistent or recurrent laryngeal squamous cell carcinoma (LSCC), there is a need for improved biomarkers of treatment response and survival to inform optimal treatment selection and prognostication. Herein, our primary objective was to explore correlations between tumor infiltrating lymphocytes (TILs) and PD-L1 Combined Positive Score (CPS). Secondarily, we sought to explore their combined association with survival outcomes in patients with persistent or recurrent LSCC treated with salvage surgery. MATERIALS AND METHODS: This was a retrospective cohort study at a single academic medical center. Immunohistochemistry staining for TILs and PD-L1 was performed on a tissue microarray of persistent or recurrent LSCC pathologic specimens. Correlations between TIL subsets and PD-L1 CPS were examined using Pearson's correlation coefficient and survival outcomes were analyzed with the Kaplan-Meier method and log-rank tests. RESULTS:...

Setting up clinical trials for success: Applying preclinical advances in combined TGFβ/PD‐L1 inhibition to ongoing clinical studies