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1.
Nat Metab ; 6(1): 78-93, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38191667

ABSTRACT

The coexistence of brown adipocytes with low and high thermogenic activity is a fundamental feature of brown adipose tissue heterogeneity and plasticity. However, the mechanisms that govern thermogenic adipocyte heterogeneity and its significance in obesity and metabolic disease remain poorly understood. Here we show that in male mice, a population of transcription factor jun-B (JunB)-enriched (JunB+) adipocytes within the brown adipose tissue exhibits lower thermogenic capacity compared to high-thermogenic adipocytes. The JunB+ adipocyte population expands in obesity. Depletion of JunB in adipocytes increases the fraction of adipocytes exhibiting high thermogenic capacity, leading to enhanced basal and cold-induced energy expenditure and protection against diet-induced obesity and insulin resistance. Mechanistically, JunB antagonizes the stimulatory effects of PPARγ coactivator-1α on high-thermogenic adipocyte formation by directly binding to the promoter of oestrogen-related receptor alpha, a PPARγ coactivator-1α downstream effector. Taken together, our study uncovers that JunB shapes thermogenic adipocyte heterogeneity, serving a critical role in maintaining systemic metabolic health.


Subject(s)
Insulin Resistance , Mice , Male , Animals , PPAR gamma/metabolism , Adipocytes, Brown/metabolism , Obesity/etiology , Obesity/metabolism , Diet, High-Fat , Transcription Factors/genetics , Transcription Factors/metabolism
2.
Am J Otolaryngol ; 45(1): 104102, 2024.
Article in English | MEDLINE | ID: mdl-37948827

ABSTRACT

OBJECTIVE: The presence of occult nodal metastases in patients with squamous cell carcinoma (SCC) of the oral tongue has implications for treatment. Upwards of 30% of patients will have occult nodal metastases, yet a significant number of patients undergo unnecessary neck dissection to confirm nodal status. This study sought to predict the presence of nodal metastases in patients with SCC of the oral tongue using a convolutional neural network (CNN) that analyzed visual histopathology from the primary tumor alone. METHODS: Cases of SCC of the oral tongue were identified from the records of a single institution. Only patients with complete pathology data were included in the study. The primary tumors were randomized into 2 groups for training and testing, which was performed at 2 different levels of supervision. Board-certified pathologists annotated each slide. HALO-AI convolutional neural network and image software was used to perform training and testing. Receiver operator characteristic (ROC) curves and the Youden J statistic were used for primary analysis. RESULTS: Eighty-nine cases of SCC of the oral tongue were included in the study. The best performing algorithm had a high level of supervision and a sensitivity of 65% and specificity of 86% when identifying nodal metastases. The area under the curve (AUC) of the ROC curve for this algorithm was 0.729. CONCLUSION: A CNN can produce an algorithm that is able to predict nodal metastases in patients with squamous cell carcinoma of the oral tongue by analyzing the visual histopathology of the primary tumor alone.


Subject(s)
Carcinoma, Squamous Cell , Tongue Neoplasms , Humans , Artificial Intelligence , Tongue Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Tongue/pathology , Neck Dissection/methods , Retrospective Studies , Lymph Nodes/pathology , Neoplasm Staging
3.
Ann Otol Rhinol Laryngol ; 132(11): 1373-1379, 2023 Nov.
Article in English | MEDLINE | ID: mdl-36896865

ABSTRACT

OBJECTIVES: The presence of nodal metastases in patients with papillary thyroid carcinoma (PTC) has both staging and treatment implications. However, lymph nodes are often not removed during thyroidectomy. Prior work has demonstrated the capability of artificial intelligence (AI) to predict the presence of nodal metastases in PTC based on the primary tumor histopathology alone. This study aimed to replicate these results with multi-institutional data. METHODS: Cases of conventional PTC were identified from the records of 2 large academic institutions. Only patients with complete pathology data, including at least 3 sampled lymph nodes, were included in the study. Tumors were designated "positive" if they had at least 5 positive lymph node metastases. First, algorithms were trained separately on each institution's data and tested independently on the other institution's data. Then, the data sets were combined and new algorithms were developed and tested. The primary tumors were randomized into 2 groups, one to train the algorithm and another to test it. A low level of supervision was used to train the algorithm. Board-certified pathologists annotated the slides. HALO-AI convolutional neural network and image software was used to perform training and testing. Receiver operator characteristic curves and the Youden J statistic were used for primary analysis. RESULTS: There were 420 cases used in analyses, 45% of which were negative. The best performing single institution algorithm had an area under the curve (AUC) of 0.64 with a sensitivity and specificity of 65% and 61% respectively, when tested on the other institution's data. The best performing combined institution algorithm had an AUC of 0.84 with a sensitivity and specificity of 68% and 91% respectively. CONCLUSION: A convolutional neural network can produce an accurate and robust algorithm that is capable of predicting nodal metastases from primary PTC histopathology alone even in the setting of multi-institutional data.


Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Humans , Artificial Intelligence , Carcinoma, Papillary/surgery , Carcinoma, Papillary/pathology , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Neck Dissection , Neural Networks, Computer , Retrospective Studies , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/pathology , Thyroidectomy/methods
4.
Am J Surg ; 222(5): 952-958, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34030870

ABSTRACT

BACKGROUND: The presence of nodal metastases is important in the treatment of papillary thyroid carcinoma (PTC). We present our experience using a convolutional neural network (CNN) to predict the presence of nodal metastases in a series of PTC patients using visual histopathology from the primary tumor alone. METHODS: 174 cases of PTC were evaluated for the presence or absence of lymph metastases. The artificial intelligence (AI) algorithm was trained and tested on its ability to discern between the two groups. RESULTS: The best performing AI algorithm demonstrated a sensitivity and specificity of 94% and 100%, respectively, when identifying nodal metastases. CONCLUSION: A CNN can be used to accurately predict the likelihood of nodal metastases in PTC using visual data from the primary tumor alone.


Subject(s)
Artificial Intelligence , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/pathology , Algorithms , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neural Networks, Computer , ROC Curve , Sensitivity and Specificity , Thyroid Cancer, Papillary/diagnosis , Thyroid Gland/pathology , Thyroid Neoplasms/diagnosis
5.
Ann Otol Rhinol Laryngol ; : 34894211014794, 2021 May 25.
Article in English | MEDLINE | ID: mdl-34032125

ABSTRACT

OBJECTIVE(S): To review the experience of 3 hospitals with airway management during surgery for substernal goiter and identify preoperative factors that predict the need for advanced airway management techniques. METHODS: A retrospective chart review between 2009 and 2017 of patients with substernal goiter treated surgically at 1 of 3 hospitals was performed. RESULTS: Of the 179 patients included in the study, 114 (63.7%) were female, the mean age was 55.1 years (range 20-87). Direct laryngoscopy or videolaryngoscopy was successful in 162 patients (90.5%), with fiberoptic intubation used for the remaining 17 patients. Thirty-one patients (17.4%) required >1 intubation attempt; these patients had larger thyroids (201.3 g, 95% CI 155.3-247.2 g) than those intubated with 1 attempt (144.7 g, 95% CI 127.4-161.9 g, P = .009). Those who required >1 attempt had higher BMI (38.3, 95% CI 34.0-42.6 vs. 32.9, 95% CI 31.5-34.3, P = .02). Mallampati score was found to be a predictor of >1 attempt, though tracheal compression and tracheal shift were not found to be predictors of >1 attempt, nor was the lowest thyroid extent. BMI was the only independent factor on multivariable logistic regression of needing >1 attempt (odds ratio 1.056, 95% CI 1.011-1.103, P = .015). CONCLUSIONS: The majority of patients undergoing surgery for substernal goiter can be intubated routinely without the need for fiberoptic intubation. Thyroid-specific factors such as lowest thyroid extent and mass effect of the gland on the trachea do not appear to be associated with difficult intubation, whereas classic patient factors associated with difficulty intubation are. LEVEL OF EVIDENCE: VI.

7.
JAMA Otolaryngol Head Neck Surg ; 141(9): 816-21, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26312435

ABSTRACT

IMPORTANCE: We present what we believe to be the first case series in which the teres major muscle is used as a free flap in head and neck reconstruction. OBJECTIVES: To describe our experience with the teres major muscle in free flap reconstruction of head and neck defects and to identify advantages of this approach. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was performed at 2 tertiary care centers between February 1, 2007, and June 30, 2012. Data analysis was conducted from July 31, 2014, through December 1, 2014. INTERVENTION: Teres major muscle free flap for use in head and neck reconstruction. MAIN OUTCOMES AND MEASURES: Indications for use, complications, and outcomes including donor site morbidity. RESULTS: The teres major free flap was used in 11 patients as a component of chimeric subscapular system free flaps for a variety of complex head and neck defects. The teres major muscle was used to fill soft-tissue defects of the neck, face, and nasal cavity; it provided substantial soft-tissue volume but was less bulky than the latissimus dorsi muscle. The teres major muscle was also used to provide protection for vascular anastomoses and/or great vessels and to enhance soft-tissue coverage of the mandibular reconstruction plate. In addition, the muscle was selected as a substrate for skin grafting where inadequate neck skin remained. Flap survival occurred in 10 of 11 flaps (91%). Two flaps (18%) demonstrated venous congestion that was managed successfully. Two patients (18%) developed minor recipient-site complications (submental fistula and infection with recurrent wound dehiscence and plate exposure). All donor sites healed well, with chronic, mild shoulder pain noted in 2 patients (18%) and no postoperative seromas observed in any patient. CONCLUSIONS AND RELEVANCE: Addition of the teres major muscle to a subscapular system free flap is an option for reconstruction of a variety of complex head and neck defects, particularly when a moderate amount of soft tissue is required. In select cases, the teres major muscle may have advantages over the latissimus dorsi muscle.


Subject(s)
Free Tissue Flaps/surgery , Myocutaneous Flap/surgery , Otorhinolaryngologic Diseases/surgery , Otorhinolaryngologic Neoplasms/surgery , Plastic Surgery Procedures/methods , Transplantation Chimera , Adult , Aged , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Female , Free Tissue Flaps/blood supply , Graft Survival , Humans , Male , Mandibular Neoplasms/pathology , Mandibular Neoplasms/surgery , Mandibular Reconstruction/methods , Microsurgery/methods , Middle Aged , Myocutaneous Flap/blood supply , Neoplasm Staging , Osteoradionecrosis/surgery , Otorhinolaryngologic Diseases/pathology , Otorhinolaryngologic Neoplasms/pathology , Postoperative Complications/etiology
8.
Otolaryngol Head Neck Surg ; 144(6): 891-3, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21493326

ABSTRACT

OBJECTIVE: Tragal pumping is the practice of pushing on the tragus to raise pressure in the external auditory canal. This is a study to determine if tragal pumping improves middle ear penetration of ototopical medications via a patent pressure equalization tube. STUDY DESIGN: Prospective, randomized controlled trial. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Children with chronic otitis media scheduled for routine placement of bilateral pressure equalization tubes were offered enrollment in the study. After pressure equalization tube insertion, an otic preparation of 0.3% ofloxacin solution dyed with methylene blue was applied sequentially to both ear canals by the operating surgeon. Tragal pumping was performed on the experimental ear, and the opposite ear served as a control. A second operator, blinded to the randomization process, used an operating microscope to determine if otic drops had entered the middle ear as demonstrated by methylene blue staining of the promontory mucosa. RESULTS: Twenty-four patients with a mean age of 3.6 years were enrolled in the study. Middle ear penetration of otic drops was present in 33% (8/24) of control ears and in 75% (18/24) of experimental ears, resulting in a statistically significant difference (P = .0094). CONCLUSION: Tragal pumping improves the middle ear penetration of ototopical medications via a patent pressure equalization tube.


Subject(s)
Ear Canal , Middle Ear Ventilation/methods , Ofloxacin/administration & dosage , Otitis Media/therapy , Anti-Bacterial Agents/administration & dosage , Child , Child, Preschool , Chronic Disease , Double-Blind Method , Female , Follow-Up Studies , Humans , Male , Prospective Studies , Treatment Outcome
9.
J Grad Med Educ ; 3(3): 414-6, 2011 Sep.
Article in English | MEDLINE | ID: mdl-22942976

ABSTRACT

BACKGROUND: The objective of this study was to determine the extent of interest in international electives among prospective otolaryngology residents and to determine whether the availability of international electives affected students' interest in ranking a particular residency program. METHODS: A 3-part survey was given to all medical students enrolled in the 2008 otolaryngology match via the Electronic Residency Application Service. Part 1 elicited demographic information. Part 2 explored general interest in international rotations. Part 3 involved ranking several factors affecting students' choice of residency programs. This survey was developed at our institution, with no formal validation. Participation was anonymous and voluntary. RESULTS: A total of 307 students entered the otolaryngology match, and 55 surveys (18%) were completed. Twenty-five of 55 students (55%) had completed an international elective during or prior to medical school, and 51 of 55 respondents (93%) had a "strong" or "very strong" desire to participate in an international elective during residency; 48 of 55 students (87%) had a "strong" or "very strong" desire to participate in international surgical missions after residency. Future practice goals had no correlation with interest in international rotations, either during or after residency training. Respondents ranked 8 factors that had an impact on residency program selection in the following order of importance: operative experience, location, lifestyle, research opportunities, didactics, international electives, prestige of program, and salary. CONCLUSION: Interest in international medicine among prospective otolaryngologists was high in this subset of respondents but did not appear to affect residency program selection.

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