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Differentiation of proinflammatory CD4+ conventional T cells (Tconv) is critical for productive antitumor responses yet their elicitation remains poorly understood. We comprehensively characterized myeloid cells in tumor draining lymph nodes (tdLN) of mice and identified two subsets of conventional type-2 dendritic cells (cDC2) that traffic from tumor to tdLN and present tumor-derived antigens to CD4+ Tconv, but then fail to support antitumor CD4+ Tconv differentiation. Regulatory T cell (Treg) depletion enhanced their capacity to elicit strong CD4+ Tconv responses and ensuing antitumor protection. Analogous cDC2 populations were identified in patients, and as in mice, their abundance relative to Treg predicts protective ICOS+ PD-1lo CD4+ Tconv phenotypes and survival. Further, in melanoma patients with low Treg abundance, intratumoral cDC2 density alone correlates with abundant CD4+ Tconv and with responsiveness to anti-PD-1 therapy. Together, this highlights a pathway that restrains cDC2 and whose reversal enhances CD4+ Tconv abundance and controls tumor growth.
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Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Animais , Antígenos de Neoplasias/imunologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Citocinas/metabolismo , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Toxina Diftérica/imunologia , Fatores de Transcrição Forkhead/metabolismo , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Linfonodos/imunologia , Linfonodos/metabolismo , Ativação Linfocitária , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Quimiocinas/metabolismo , Linfócitos T Reguladores/imunologia , Microambiente TumoralRESUMO
Objective: There is limited data on the impact of clinical-demographic factors on survival outcomes among veterans with head and neck squamous cell carcinoma (HNSCC). This study was undertaken to evaluate the impact of race and other factors on overall survival (OS) in a population of veterans with HNSCC treated with curative intent. Methods: Demographic and clinical data were collected on veterans with HNSCC treated with curative intent at our institution between 1999 and 2021. The primary outcome was 3-year OS. Secondary outcomes included treatment delay intervals, including time to treatment initiation (TTI), total package time, and duration of chemoradiation (DCRT). Results: Of 260 veterans with HNSCC, black veterans had significantly lower 3-year OS (49.4%) compared to white veterans (65%, P = .019). Black veterans were also more likely to experience delays in treatment initiation (median TTI 46 vs 41 days; P = .047). Black patients were more likely to receive radiation alone (25.8% [black] vs 8.4% [white]; P < .001) and less likely to receive adjuvant therapy if treated surgically (11.1% [black] vs 22.4% [white]; P = .004), despite any statistically significant difference in stage of their tumor at presentation (Stage I: 21.2% [black] vs 19.6% [white]; P = .372); (Stage IV: 44.4% [black] vs 48.6% [white]; P = .487). Other factors associated with worse 3-year OS included older age (P = .023), lower body mass index (P = .026), neurocognitive disorder/dementia (P = .037), mental health disorders (P = .020), hypopharyngeal primary (P = .001), higher stage disease (P = .002), treatment type (P = .001), need for prophylactic gastrostomy tube (P = .048) or tracheotomy (P = .005), recurrent disease (P = .036), persistent disease (P < .001), distant metastases (P = .002), longer TTI (P = .0362), and longer DCRT (P = .004). Discussion: Black race appears to be an independent predictor of 3-year OS in veterans with HNSCC. Further studies are warranted to determine the factors responsible for disparities in survival. Implications for Practice: This study evaluated the ways in which race affects survival for US veterans with head and neck cancer. The authors found that black veterans had an increased risk of death compared to white patients, and also experienced delays when receiving treatment. Level of Evidence: Level IV.
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Importance: Postoperative radiation therapy for close surgical margins in low- to intermediate-grade salivary carcinomas lacks multi-institutional supportive evidence. Objective: To evaluate the oncologic outcomes for low- and intermediate-grade salivary carcinomas with close and positive margins. Design, Setting, and Participants: The American Head and Neck Society Salivary Gland Section conducted a retrospective cohort study from 2010 to 2019 at 41 centers. Margins were classified as R0 (negative), R1 (microscopically positive), or R2 (macroscopically positive). R0 margins were subclassified into clear (>1 mm) or close (≤1 mm). Data analysis was performed from June to October 2023. Main Outcomes and Measures: Main outcomes were risk factors for local recurrence. Results: A total of 865 patients (median [IQR] age at surgery, 56 [43-66] years; 553 female individuals [64%] and 312 male individuals [36%]) were included. Of these, 801 (93%) had parotid carcinoma and 64 (7%) had submandibular gland carcinoma, and 748 (86%) had low-grade tumors and 117 (14%) had intermediate-grade tumors, with the following surgical margins: R0 in 673 (78%), R1 in 168 (19%), and R2 in 24 (3%). Close margins were found in 395 of 499 patients with R0 margins (79%), for whom margin distances were measured. A total of 305 patients (35%) underwent postoperative radiation therapy. Of all 865 patients, 35 (4%) had local recurrence with a median (IQR) follow-up of 35.3 (13.9-59.1) months. In patients with close margins as the sole risk factor for recurrence, the local recurrence rates were similar between those who underwent postoperative radiation therapy (0 of 46) or observation (4 of 165 [2%]). Patients with clear margins (n = 104) had no recurrences. The local recurrence rate in patients with R1 or R2 margins was better in those irradiated (2 of 128 [2%]) compared to observed (13 of 64 [20%]) (hazard ratio [HR], 0.05; 95% CI, 0.01-0.24). Multivariable analysis for local recurrence found the following independent factors: age at diagnosis (HR for a 10-year increase in age, 1.33; 95% CI, 1.06-1.67), R1 vs R0 (HR, 5.21; 95% CI, 2.58-10.54), lymphovascular invasion (HR, 4.47; 95% CI, 1.43-13.99), and postoperative radiation therapy (HR, 0.10; 95% CI, 0.04-0.29). The 3-year local recurrence-free survivals for the study population were 96% vs 97% in the close margin group. Conclusions and Relevance: In this cohort study of patients with low- and intermediate-grade major salivary gland carcinoma, postoperative radiation therapy for positive margins was associated with decreased risk of local recurrence. In isolation from other risk factors for local recurrence, select patients with close surgical margins (≤1 mm) may safely be considered for observation.
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Carcinoma , Neoplasias das Glândulas Salivares , Humanos , Masculino , Feminino , Lactente , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Estudos de Coortes , Margens de Excisão , Carcinoma/cirurgia , Neoplasias das Glândulas Salivares/radioterapia , Neoplasias das Glândulas Salivares/cirurgia , Neoplasias das Glândulas Salivares/patologiaRESUMO
BACKGROUND: Head and neck cancer patients are at risk for malnutrition, which can impact postoperative outcomes. This study evaluates the Malnutrition Universal Screening Tool (MUST) to predict outcomes in major head and neck surgeries. METHODS: A retrospective chart review included 275 major surgical procedures performed on 242 patients over the age of 18 years between May 2015 and May 2020. RESULTS: The majority of patients had a MUST score of zero (68.7%). Just under 17% scored 2 or greater indicating malnourishment. Having a MUST score of 2 or higher was associated with occurrence of a postoperative complication (p < 0.001). Patients with alcohol use disorder or depression were 5.2 (CI: 2.0-13.7, p = 0.001) and 2.75 (CI 1.1-7.0; p = 0.033) times more likely to develop a postoperative complication, respectively. CONCLUSIONS: Malnutrition and comorbidities were associated with complications in our surgical cohort. MUST is a novel tool to identify patients who may benefit from nutritional interventions.
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Neoplasias de Cabeça e Pescoço , Desnutrição , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Detecção Precoce de Câncer , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/cirurgia , Fatores de RiscoRESUMO
OBJECTIVES: To report a case of ingested wire bristle embedded within the extrinsic musculature of the tongue requiring a transcervical approach for removal and to provide a revised algorithm for the management of ingested wire bristles. METHODS: The clinical record of 1 patient who ingested a grill brush wire bristle was reviewed. A literature review was also conducted to refine a treatment algorithm for managing ingested wire bristles. RESULTS: We present a case of a 53-year-old male who accidentally ingested a grill brush wire bristle. After multiple unsuccessful endoscopic attempts at removal, the wire bristle migrated deep into the extrinsic musculature of the tongue, necessitating a transcervical approach for adequate visualization and retrieval. CONCLUSIONS: This is the first case reported of a wire bristle migrating deep into the tongue musculature that was successfully removed via a transcervical approach. Our proposed algorithm provides a comprehensive approach to the management of ingested wire bristles, specifically in cases where endoscopic retrieval is not feasible.
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Corpos Estranhos , Laringe , Masculino , Humanos , Pessoa de Meia-Idade , Língua/cirurgia , Laringoscopia , Corpos Estranhos/cirurgia , AlgoritmosRESUMO
Objectives: Investigate opioid usage and postoperative pain in patients undergoing head and neck free flap surgery. Methods: A retrospective review of 100 consecutive patients undergoing head and neck free flap reconstruction at two academic centers was performed. Data captured included demographics, postoperative inpatient pain, pain at postoperative visits, morphine equivalent doses (MEDs) administration, medication history, and comorbidities. Data were analyzed using regression models, χ 2 tests, and student's t-tests. Results: Seventy-three percent of patients were discharged with opioid medication, with over half (53.4%) continuing to take opioids at their second postoperative visit, and over one-third (34.2%) continuing to take them around 4-month postoperatively. One out of every five (20.3%) opioid-naïve patients chronically took opioids postoperatively. There was a poor association between inpatient postoperative pain scores and daily MEDs administered (R 2 = 0.13, 0.17, and 0.22 in postoperative Days 3, 5, and 7, respectively). Neither preoperative radiotherapy nor postoperative complications were associated with an increase in opioid usage. Conclusions: For patients undergoing head and neck free flap operations, opioid medications are commonly used for postoperative analgesia. This practice may increase the chance an opioid-naïve patient uses opioids chronically. We found a poor association between MEDs administered and patient-reported pain scores, which suggests that standardized protocols aimed at optimizing analgesia while reducing opioid administration may be warranted. Level of Evidence: 3 (Retrospective cohort study).
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BACKGROUND: Patients undergoing surgery for head and neck cancer (HNC) have potentially high perioperative complication rates. Recent studies indicate that preoperative COVID-19 infection poses increased risk for postoperative complications in other fields. However, to date, there has not been data showing the effect of COVID-19 on complication rates for HNC. Here, a large database was employed to assess if perioperative COVID-19 increased the risk of perioperative complications among those undergoing HNC surgery. METHODS: A retrospective investigation was conducted using a multi-institutional research database. Subjects who underwent HNC surgery from January 2020 to September 2022 were identified using the International Classification of Diseases and Current Procedure Terminology codes. Thirty-day surgical and medical complications were assessed for those diagnosed with COVID-19 infection from 7 days before or after surgery compared to those who were COVID-19 negative. Cohorts were propensity scores matched by age, sex, and race. RESULTS: Perioperative COVID-19 was present in n = 208 and absent in n = 15 158 subjects that underwent HNC surgery. For unmatched analyses, there was a statistically significant increased risk in the 30-day postoperative period in COVID-19-positive patients for the following surgical complications: surgical site fistula, free tissue transfer (FTT) complication, FTT failure, and death. Additionally, there was a statistically significant increased risk in the 30-day postoperative period in COVID-19-positive patients for the following medical complications: ventilator support, pneumonia, vasopressor, acute renal failure, and myocardial infarction. CONCLUSION: This large, retrospective populational study suggests HNC patients are at increased risk for death and several perioperative complications. This investigation is the first to address this clinical question.
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COVID-19 , Neoplasias de Cabeça e Pescoço , Infarto do Miocárdio , Humanos , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/complicações , Infarto do Miocárdio/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Estudos Multicêntricos como AssuntoRESUMO
Introduction As the limits of advanced skull base malignancies that can be managed through an endoscopic endonasal approach continue to be expanded, the resultant anterior skull base defects are of increasing size and complexity. In the absence of nasoseptal or turbinate flaps, the vascularized pericranial flap has been employed at our institution with excellent results. Objective The study aimed to review the outcomes of patients who underwent endonasal anterior craniofacial resection with anterior skull base reconstruction using a vascularized pericranial flap. Design Retrospective chart review of patients treated by the University of California - San Francisco minimally invasive skull base service from the years 2011 to 2017. Average duration of follow-up was 16.4 months. Setting This study was conducted at Academic tertiary referral center. Participants A total of nine patients with advanced anterior cranial base malignancies were identified who were treated with a minimally invasive, endoscopic anterior craniofacial resection from the years 2011 to 2017. Due to the nature of the resection in these patients, nasoseptal flaps and inferior/middle turbinate flaps were unavailable or insufficient for anterior skull base defect repair. Each patient underwent reconstruction of the anterior cranial base defect using an anteriorly based pericranial flap harvested by bicoronal incision, and tunneled anteriorly to the nasal cavity through a frontoethmoidal incision.
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While the use of image-guided navigation is an excellent adjunct to the use of anatomical landmarks, dynamic changes that may occur in the position of critical structures are not accounted for during and after tumor resection. Unlike navigation, Doppler ultrasonography provides real-time imaging of the anterior skull base and can be used to accurately identify the location of vital structures during skull base surgery. A 56-year-old female initially presented with new onset left eye visual deficits. She previously underwent sublabial transsphenoidal subtotal resection of the tumor, confirmed as clival chordoma. She subsequently presented to our institution. She was treated with an expanded endonasal resection of the remaining chordoma followed by CyberKnife radiosurgery. Two years later, surveillance imaging identified tumor recurrence within the right clivus posterior to the carotid artery. Intraoperatively, in the previously operated irradiated skull base, the normal bony architecture of the sella was absent, resulting in the inability to distinguish the anterior genu of the internal carotid artery (ICA) from the adjacent tumor. Using Doppler ultrasonography, the course of the ICA was imaged in real time, allowing for safe, gross total tumor resection. In the setting of prior operation, radiation, or extensive disease, the normal bony architecture of the sella may be disrupted, placing the cavernous ICA at risk. We report what we believe is the first use of intraoperative ultrasound during the endoscopic endonasal approach in the setting of a previously operated, radiated sella.
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OBJECTIVE: To determine if there is an association between authors' financial conflict of interest and published position on clinical use of hypoglossal nerve stimulation for obstructive sleep apnea. STUDY DESIGN: Retrospective cross-sectional analysis. SETTING: International roster of authors and articles analyzed. METHODS: A Google Scholar search was performed for editorials and reviews citing the 2014 New England Journal of Medicine article on hypoglossal nerve stimulation for obstructive sleep apnea. Included articles were coded as favorable or neutral. Conflict of interest was recorded as declared by the authors in these articles and as independently searched in the Open Payments registry. RESULTS: Sixteen articles from 45 independent authors were analyzed. Nine articles by authors were coded as favorable. Among authors of articles with favorable views, 16 (59%) had a financial conflict of interest with the manufacturer of the hypoglossal nerve stimulator device, as opposed to only 1 of 21 (5%) authors of neutral/unfavorable articles. When we included only authors to whom payments could be identified or excluded on Open Payments, 16 of 20 (80%; 95% CI, 62%-98%) authors of favorable articles had a financial conflict, while 1 of 10 (10%; 95% CI, 0%-29.6%) of neutral/unfavorable articles did (P = .004). CONCLUSION: Our study demonstrates an association between published position on hypoglossal nerve stimulator use and financial conflict with the device manufacturer. Several undeclared conflicts were also found, suggesting a role for independent search for conflicts during the review process.
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Conflito de Interesses/economia , Terapia por Estimulação Elétrica , Apoio Financeiro/ética , Nervo Hipoglosso , Síndromes da Apneia do Sono/terapia , Estudos Transversais , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVES: To present a novel location in which neurosarcoidomatous inflammation is identified and its accompanying presentation. METHODS: The authors present a case of bilateral vocal fold paresis associated with non-caseating granulomatous inflammation of the cervical and intra-axial portions of the vagus nerve masquerading as a cranial nerve tumor. RESULTS: Examination revealed bilateral vocal fold paresis and asymmetric palate elevation. MRI demonstrated enhancing bilateral jugular foramen masses, and neck ultrasound demonstrated bilateral thickened appearance of the vagus nerves. Vagus nerve biopsy demonstrated non-caseating granulomas. CONCLUSIONS: Neurosarcoidosis may contribute to variable cranial neuropathies. Vocal fold paresis is usually thought to arise from mediastinal compression of the left recurrent laryngeal nerve. Rarely, though, lesions may arise in other parts of the vagus nerve. Failure of response to steroids does not rule out the diagnosis, making tissue diagnosis important in some cases.
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Doenças do Sistema Nervoso Central/diagnóstico , Sarcoidose/diagnóstico , Nervo Vago/diagnóstico por imagem , Nervo Vago/patologia , Paralisia das Pregas Vocais/etiologia , Biópsia , Feminino , Granuloma/diagnóstico por imagem , Granuloma/etiologia , Humanos , Forâmen Jugular/diagnóstico por imagem , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , UltrassonografiaRESUMO
OBJECTIVE: To report the prevalence of intratonsillar abscess in the pediatric population at our institution and demonstrate that intratonsillar abscess is a more commonly encountered diagnosis than previously reported. METHODS: A retrospective chart review was performed that included patients presenting to our pediatric tertiary referral academic emergency department from January 1, 2014 to December 31, 2014 diagnosed with intratonsillar abscess on computed tomography. RESULTS: In the year 2014, 22 children were diagnosed with intratonsillar abscess by radiological criteria. The majority of patients (82%) required no surgical intervention and were successfully treated with antibiotics and supportive measures. All patients recovered from the infection uneventfully, and there were no treatment complications recorded. CONCLUSION: Even in recent literature, intratonsillar abscess is described as a rare entity, with few cases reported. In our experience, CT imaging demonstrating the presence of intratonsillar abscess is more common than previously described. Regardless of treatment method, in our experience children with intratonsillar abscess do well clinically.
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Abscesso/epidemiologia , Tonsila Palatina , Abscesso/diagnóstico por imagem , Abscesso/tratamento farmacológico , Adolescente , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Prevalência , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Duplication of the anterior skull base structures is an extremely rare malformation of failed midline blastogenesis. We present the case of a child with an obstructive oral cavity mass diagnosed on prenatal imaging. The child was successfully delivered by EXIT procedure, a tracheotomy was performed, and postnatal imaging demonstrated an array of craniofacial malformations, including complete duplication of the maxilla, pituitary glands, aqueducts of Sylvius, and basilar arteries. The child underwent excision of the duplicate maxilla, resulting in a wide cleft palate that will be repaired at a future date.
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Anormalidades Múltiplas/cirurgia , Anormalidades Craniofaciais/cirurgia , Base do Crânio/anormalidades , Anormalidades Múltiplas/diagnóstico por imagem , Artéria Basilar/anormalidades , Aqueduto do Mesencéfalo/anormalidades , Criança , Anormalidades Craniofaciais/diagnóstico por imagem , Parto Obstétrico/métodos , Feminino , Humanos , Maxila/anormalidades , Hipófise/anormalidades , Base do Crânio/diagnóstico por imagem , Traqueotomia , Ultrassonografia Pré-NatalRESUMO
Objective To review the literature concerning the management of dental needles broken off into the deep spaces of the neck, to report what we believe is the first case of a fractured dental needle migrating into the jugular foramen, and the unconventional use of endovascular intervention to retrieve the needle fragment. Design Case report with review of literature. Setting Academic tertiary care center. Participants Intervention was performed by the otolaryngology-head and neck surgery, vascular surgery, and neurovascular interventional radiology teams. Results Transoral exploration, including palatal split and exposure of the poststyloid parapharyngeal space with C-arm image guidance, was unable to retrieve the broken needle, which traversed the internal carotid lumen with the distal end entering the jugular foramen. Through endovascular intervention, the neurovascular interventional radiology team captured the proximal end of the needle and retrieved it through the femoral artery. The patient recovered uneventfully. Conclusion Fracture and loss of oral injection needles remain a persistent and preventable problem. This case demonstrates a novel, minimally invasive, well-tolerated, and successful method to extract a fractured needle that migrated into the lumen of the internal carotid artery at the level of the skull base.
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OBJECTIVES/HYPOTHESIS: Spontaneous occurrence of otogenic cerebrospinal fluid (CSF) effusion is now far more prevalent than causes related to infections, prior surgeries, or trauma-trends that may be increasing because of higher rates of obesity and improved diagnostic awareness. In our patient cohort with spontaneous CSF effusion, we report its association with obesity and audiological findings before and after surgery. STUDY DESIGN: Retrospective study. METHODS: In our 45 patients (46 ears) with CSF effusion (with or without lateral skull base meningoencephaloceles), we report clinical data, imaging studies, audiogram results, operative techniques, and recurrence rates. Causes included 33 spontaneous, 10 due to chronic otitis media, one iatrogenic, and one traumatic. RESULTS: Body mass index (BMI) averaged 35 overall (37 for spontaneous type and 32 for nonspontaneous type). Surgical repair of skull base defect was performed using three middle fossa approaches, 24 combined transmastoid/middle fossa, and 19 transmastoid alone. Overall recurrence of CSF leaks was 6.5%. Thirty patients had audiograms available. Sensorineural hearing loss occurred in 10% of patients. Air-bone gap improved by ≥ 15 dB in 20% of patients and worsened by ≥ 15 dB in 6.7% of patients. CONCLUSION: Patients with spontaneous CSF effusion had a BMI higher than in the nonspontaneous group, but the difference was not statistically significant. However, the dramatic trend toward spontaneous CSF effusion heightens the need for clinician's acumen for diagnosis, particularly in overweight/obese patients. Our audiological outcomes confirm the efficacy of surgical approaches in correcting conductive hearing loss and preserving bone conduction, although hearing loss is a risk during surgical repair. LEVEL OF EVIDENCE: 4. Laryngoscope, 124:1204-1208, 2014.