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1.
World Neurosurg ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38734166

RESUMEN

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor predominantly arising in soft tissue. We report a rare case of thoracic spinal EHE with pulmonary metastasis. METHODS: Case report and systematic review of spinal EHE. RESULTS: A 36-year-old man presented with bilateral lower extremity weakness, progressive paresthesia, and urinary incontinence. He underwent open surgical resection of the tumor and decompression of the spinal cord, with subsequent improvement in neurological function. Systematic review identified 84 cases of spinal EHE, 73 of which were primary, and 14 of which developed extra-spinal metastases. CONCLUSION: EHE is an exceedingly rare tumor that may present with a wide swath of clinical symptoms. At present, no guidelines or formal treatment recommendations have been established. Surgical debulking has demonstrated efficacy as a front-line treatment, particularly in the setting of compressive neurological dysfunction; data regarding adjuvant chemoradiation are less consistently reported, mandating further study.

2.
J Clin Neurosci ; 125: 106-109, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38763077

RESUMEN

OBJECTIVE: To determine the incidence of vasospasm in traumatic brain injury patients with traumatic subarachnoid hemorrhage. METHODS: IRB approval was obtained for this retrospective chart review. An institutional trauma database was queried for adult patients with traumatic brain injury (TBI) and traumatic subarachnoid hemorrhage (tSAH) seen on CT head obtained within 20 days. The presence of vasospasm on CTA was determined by radiology report. Association between categorical background characteristics and intracranial vasospasm was assessed by the chi-square test and association between a continuous variables and intracranial vasospasm was assessed by a paired t-test. RESULTS: 1142 patients with traumatic SAH were identified from the trauma database. 792 patients were excluded: 142 for age <18, 632 did not have CT angiography, and 18 had non-traumatic SAH. 350 patients were analyzed, of which 28 (8 %) had vasospasm. Traumatic vasospasm was associated with higher-grade TBI based on Cochran-Armitage trend test (p < 0.05). Vasospasm patients had longer length of stay in the ICU (mean days 13.64 vs 7.24, P < 0.001), and had a higher incidence of death (39.29 % vs 20.81 %), although this did not reach statistical significance. CONCLUSION: Intracranial vasospasm, specifically in patients with tSAH, is associated with more severe TBI and longer stays in the ICU. Our incidence is smaller compared to other studies likely due to the retrospective nature and the infrequency of obtaining CT angiography after initial presentation. Prospective studies are warranted as the incidence is significant and may represent a point of intervention for TBI.

3.
bioRxiv ; 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38617365

RESUMEN

The plant corepressor TPL is recruited to diverse chromatin contexts, yet its mechanism of repression remains unclear. Previously, we have leveraged the fact that TPL retains its function in a synthetic transcriptional circuit in the yeast model Saccharomyces cerevisiae to localize repressive function to two distinct domains. Here, we employed two unbiased whole genome approaches to map the physical and genetic interactions of TPL at a repressed locus. We identified SPT4, SPT5 and SPT6 as necessary for repression with the SPT4 subunit acting as a bridge connecting TPL to SPT5 and SPT6. We also discovered the association of multiple additional constituents of the transcriptional preinitiation complex at TPL-repressed promoters, specifically those involved in early transcription initiation events. These findings were validated in yeast and plants through multiple assays, including a novel method to analyze conditional loss of function of essential genes in plants. Our findings support a model where TPL nucleates preassembly of the transcription activation machinery to facilitate rapid onset of transcription once repression is relieved.

4.
JAMA ; 331(15): 1279-1286, 2024 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-38497992

RESUMEN

Importance: Endotracheal tubes are typically inserted in the operating room using direct laryngoscopy. Video laryngoscopy has been reported to improve airway visualization; however, whether improved visualization reduces intubation attempts in surgical patients is unclear. Objective: To determine whether the number of intubation attempts per surgical procedure is lower when initial laryngoscopy is performed using video laryngoscopy or direct laryngoscopy. Design, Setting, and Participants: Cluster randomized multiple crossover clinical trial conducted at a single US academic hospital. Patients were adults aged 18 years or older having elective or emergent cardiac, thoracic, or vascular surgical procedures who required single-lumen endotracheal intubation for general anesthesia. Patients were enrolled from March 30, 2021, to December 31, 2022. Data analysis was based on intention to treat. Interventions: Two sets of 11 operating rooms were randomized on a 1-week basis to perform hyperangulated video laryngoscopy or direct laryngoscopy for the initial intubation attempt. Main Outcomes and Measures: The primary outcome was the number of operating room intubation attempts per surgical procedure. Secondary outcomes were intubation failure, defined as the responsible clinician switching to an alternative laryngoscopy device for any reason at any time, or by more than 3 intubation attempts, and a composite of airway and dental injuries. Results: Among 8429 surgical procedures in 7736 patients, the median patient age was 66 (IQR, 56-73) years, 35% (2950) were women, and 85% (7135) had elective surgical procedures. More than 1 intubation attempt was required in 77 of 4413 surgical procedures (1.7%) randomized to receive video laryngoscopy vs 306 of 4016 surgical procedures (7.6%) randomized to receive direct laryngoscopy, with an estimated proportional odds ratio for the number of intubation attempts of 0.20 (95% CI, 0.14-0.28; P < .001). Intubation failure occurred in 12 of 4413 surgical procedures (0.27%) using video laryngoscopy vs 161 of 4016 surgical procedures (4.0%) using direct laryngoscopy (relative risk, 0.06; 95% CI, 0.03-0.14; P < .001) with an unadjusted absolute risk difference of -3.7% (95% CI, -4.4% to -3.2%). Airway and dental injuries did not differ significantly between video laryngoscopy (41 injuries [0.93%]) vs direct laryngoscopy (42 injuries [1.1%]). Conclusion and Relevance: In this study among adults having surgical procedures who required single-lumen endotracheal intubation for general anesthesia, hyperangulated video laryngoscopy decreased the number of attempts needed to achieve endotracheal intubation compared with direct laryngoscopy at a single academic medical center in the US. Results suggest that video laryngoscopy may be a preferable approach for intubating patients undergoing surgical procedures. Trial Registration: ClinicalTrials.gov Identifier: NCT04701762.


Asunto(s)
Intubación Intratraqueal , Laringoscopios , Laringoscopía , Femenino , Humanos , Masculino , Intubación Intratraqueal/efectos adversos , Intubación Intratraqueal/métodos , Laringoscopía/efectos adversos , Laringoscopía/métodos , Quirófanos , Traumatismos de los Dientes/etiología , Grabación en Video , Procedimientos Quirúrgicos Operativos , Estudios Cruzados , Persona de Mediana Edad , Anciano , Centros Médicos Académicos
5.
Artículo en Inglés | MEDLINE | ID: mdl-38336021

RESUMEN

Improved strategies in aortic valve-preserving operations appreciate the dynamic, three-dimensional complexity of the aortic root and its valve. This depends not only on detailed four-dimensional imaging of the planar dimensions of the aortic root but also on quantitative assessment of the valvar leaflets and their competency. The zones of apposition and resulting hemodynamic ventriculoarterial junction formed in diastole determine valvar competency. Current understanding and assessment of this junction is limited, often relying on intraoperative direct surgical inspection. However, this direct inspection itself is limited by evaluation in a nonhemodynamic state with limited field of view. In this review, we discuss the anatomy of the aortic root, including its hemodynamic junction. We review current echocardiographic approaches toward interrogating the incompetent aortic valve for presurgical planning. Furthermore, we introduce and standardize a complementary approach to assessing this hemodynamic ventriculoarterial junction by three-dimensional echocardiography to further personalize presurgical planning for aortic valve surgery.

6.
Horm Res Paediatr ; 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38295777

RESUMEN

INTRODUCTION: Agranulocytosis is a rare, but serious complication of methimazole (MMI) use for Graves' disease (GD). Treatment requires discontinuation of MMI, and the use of propylthiouracil (PTU) is also contraindicated. Few reports exist about the optimal alternative treatment regimens for the management of thyrotoxicosis in these medically complex patients in the pediatric population. CASE REPORT: We report prolonged saturated solution of potassium Iodide (SSKI) use (29 days) in a 17-year-old female with GD and MMI-induced agranulocytosis, who presented with septic shock. Her treatment course also included beta-blockade, cholestyramine, and granulocyte colony stimulating factor. We performed a review of the literature on the use of SSKI in the management of thyrotoxicosis, as well as best practices from the view of endocrinology, infectious disease, hematology, surgery, and intensivists, for the evaluation and management of MMI-induced agranulocytosis. DISCUSSION: The management of MMI-induced agranulocytosis and associated sequelae require subspecialty input and intensive evaluation and monitoring. Alternative treatments to manage hyperthyroidism and control symptoms of thyrotoxicosis during agranulocytosis are a bridge to definitive therapy, and include beta-blockade, SSKI, cholestyramine, steroids, lithium, and plasmapheresis.

7.
Horm Res Paediatr ; 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37956658

RESUMEN

INTRODUCTION: Radiation-induced lung injury is a rare complication of radioactive iodine therapy (RAIT) in pediatric thyroid cancer treatment. In this case report, we describe a pediatric patient with an ERC1::RET-positive classic papillary thyroid carcinoma who developed progressive respiratory symptoms and chest imaging abnormalities following RAIT for lymph node and pulmonary disease. CASE PRESENTATION: A pediatric patient with ERC1::RET-positive classic papillary thyroid carcinoma was hospitalized for pulmonary decompensation three months following one empiric dose of RAIT. Testing revealed no evidence of infection or progression of pulmonary metastases, and there was no improvement with empiric antibiotic therapy for pneumonia. Despite empiric anti-inflammatory therapies, the patient remains symptomatic from a respiratory standpoint with requirement for supplemental oxygen and evidence of fibrotic changes on chest imaging. CONCLUSIONS: This patient's pulmonary condition is consistent with radiation-induced pulmonary injury including development of pulmonary fibrosis. With the availability of RET fusion targeted inhibitors, this case highlights a rare pulmonary side effect of radioactive iodine for clinicians to recognize. Upfront targeted therapy protocols may help avoid radioactive iodine-associated adverse reactions.

8.
J Clin Ultrasound ; 51(9): 1622-1630, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37850556

RESUMEN

This scoping review analyzed statements from 22 medical organizations in the United States to identify commonalities in the definition and governance of point-of-care ultrasound (POCUS). A total of 41 statements were included. The review found that the most commonly used elements in defining POCUS were "focused," "bedside," and "patient care." In terms of governance, consistent requirements included specific training programs, documentation in medical records, continuous quality assurance, and standards for credentialing and privileging. These findings suggest the existence of essential commonalities that could facilitate communication and the development of standardized POCUS programs in the future.


Asunto(s)
Sistemas de Atención de Punto , Pruebas en el Punto de Atención , Estados Unidos , Humanos , Ultrasonografía , Habilitación Profesional
9.
J Neurosurg Case Lessons ; 6(7)2023 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-37728278

RESUMEN

BACKGROUND: Anterior choroidal artery (AChA) fusiform aneurysms are exceedingly rare and associated with high rebleeding and mortality rates. Their difficult anatomy comes with a broad range of treatment options, including bypass, stent-assisted coiling, and flow diversion. Currently, flow diverters are approved for large-caliber internal carotid artery segment aneurysms. However, many institutions have expanded their use to distal small-caliber vessels, which raises questions regarding device sizing and long-term patency. The authors present a dissecting distal AChA fusiform pseudoaneurysm treated successfully with flow diversion. OBSERVATIONS: A 40-year-old woman with monoclonal gammopathy of unknown significance, lichen sclerosis, and an unspecified connective tissue disease presented with diffuse subarachnoid hemorrhage. She had a dissecting, 5 × 3-mm, left AChA pseudoaneurysm 4 mm distal to the origin of the vessel. A 2.5-mm flow redirection endoluminal device was deployed. There were no procedural complications. A 6-month cerebral angiogram showed device patency and no pseudoaneurysm remnant. These results were maintained at 1 year as seen on head magnetic resonance angiography. LESSONS: Flow diversion is a successful and safe therapeutic intervention for challenging intracranial aneurysms originating from small-caliber vessels supplying eloquent vascular territories.

10.
Horm Res Paediatr ; : 1-11, 2023 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-37722360

RESUMEN

INTRODUCTION: Childhood cancer survivors (CCS) are at risk for radiotherapy (RT) late effects, including second malignancies. Optimal screening for differentiated thyroid cancer (DTC) in CCS post-RT remains controversial. We assessed the outcome of thyroid ultrasound (US) surveillance in CCS exposed to RT. METHODS: 306 CCS were surveilled with thyroid US between 2002-2021. Surveillance was dependent on age at the time of primary diagnosis, interval from receipt of RT, and individual provider. Thyroid US, clinicopathologic features, and outcomes were described. Cutpoints of CCS RT age associated with varying risk of nodule presentation were explored. The selected cutpoints were used to define age categories, which were then used to compare thyroid nodule-related outcomes. Risk factors for thyroid nodule(s) were evaluated using multivariate logistic regression (odds ratio [OR] [95% confidence interval]). RESULTS: The most common CCS diagnoses were leukemia (32%), CNS tumor (26%), and neuroblastoma (18%). Patients received TBI (45%) and/or RT to craniospinal (44%), chest (11%), and neck regions (6%). About 49% (n = 150) of patients had thyroid nodule(s). Forty-four patients underwent surgery, and 28 had DTC: 19 with American Thyroid Association (ATA) low-risk classification, 2 with ATA intermediate-risk, and 7 with ATA high-risk disease. Age cutpoint analyses identified cutpoints 3 and 10; hence, ≤3, >3 to ≤10, and >10 years were used. Of the 9 patients with intermediate- or high-risk disease, 8 were ≤10 years and 1 was >10 years at the time of RT. Female sex (OR = 1.62 [1.13-2.12] p = 0.054) and greater interval between RT and first US (OR = 1.10 [1.04-1.16] p = 0.001) were independent risk factors for nodule presentation. CONCLUSIONS: Thyroid US surveillance may be beneficial for CCS exposed to RT at younger ages (≤10 years) for earlier detection of DTC, prior to developing advanced metastatic disease.

11.
Interv Neuroradiol ; : 15910199231194664, 2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37593792

RESUMEN

BACKGROUND AND IMPORTANCE: In patients with vertebral artery (VA) occlusion, spontaneous flow reversal may occur in the anterior spinal artery (ASA) as a source of compensatory supply to the posterior circulation. Turbulent flow and increased flux through these small arteries may predispose to luminal damage and intracranial aneurysm formation. We report a novel case of a ruptured ASA-VA junction aneurysm in a patient with chronic bilateral VA occlusion, successfully treated with endovascular embolization. CLINICAL PRESENTATION: A 62-year-old female with uncontrolled hypertension presented with acute-onset headache, emesis, neck stiffness, and decreased level of consciousness. Head computed tomography demonstrated diffuse cisternal subarachnoid hemorrhage with intraventricular extension and ventriculomegaly. Computed tomography angiography showed left VA atresia and chronic right VA occlusion just distal to the posterior inferior cerebellar artery origin, as well as a complex, bilobed aneurysm at the ASA-VA junction. Angiography demonstrated flow reversal from the ASA into the distal stump of the occluded right VA, which in turn filled the aneurysm. Of note, the patient's posterior circulation was predominantly supplied by the dilated ASA, and associated collaterals from ASA and right VA stump. The aneurysm was accessed and embolized using superselective microcatheterization over a soft microguidewire through the right cervical VA perforators supplying retrograde flow into and through the ASA. CONCLUSION: ASA-VA aneurysms are exceedingly rare, and generally associated with atypical flow dynamics. Dynamic treatment strategies may be needed, especially in the setting of subarachnoid hemorrhage.

12.
J Biomech Eng ; 145(11)2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37470476

RESUMEN

This paper reports a nonbraided, bioresorbable polycaprolactone (PCL) flow diverter (FD) for the endovascular treatment of aneurysms. Bioresorbable FDs can reduce the risk associated with the permanent metallic FDs as they are resorbed by the body after curing of aneurysms. PCL FDs were designed and fabricated using an in-house hybrid electromelt spinning-fused deposition fabrication unit. Flow diverter's properties, surface qualities, and mechanical characteristics of PCL FDs of 50%, 60%, and 70% porosities were studied using scanning electron microscope (SEM), atomic force microscopy (AFM), and high precision universal testing machine (UTM). The deployability through a clinically relevant catheter was demonstrated in a PDMS aneurysm model. The angiographic visibility of the developed PCL FDs was evaluated using BaSO4 and Bi2O3 coatings of various concentration. The average strut thicknesses were 74.12 ± 6.63 µm, 63.07 ± 1.26 µm, and 56.82 ± 2.09 µm for PCL FDs with 50%, 60%, and 70% porosities, respectively. They average pore areas for the 50%, 60% and 70% porosities FDs were 0.055 ± 0.0056 mm2, 0. 0605 ± 0.0065 mm2, and 0.0712 ± 0.012 mm2, respectively. The surface quality was great with an RMS roughness value of 14.45 nm. The tensile, radial strength, and flexibility were found to be satisfactory and comparable to the nonbraided coronary stents. The developed PCL FDs were highly flexible and demonstrated to be deployable through conventional delivery system as low as 4 Fr catheters in a PDMS aneurysm model. The visibility under X-ray increases with the increasing concentration of coating materials BaSO4 and Bi2O3. The visibility intensity was slightly higher with Bi2O3 coating of PCL FDs. The overall results of the engineering analysis of the developed nonbraided PCL FDs are promising.


Asunto(s)
Procedimientos Endovasculares , Aneurisma Intracraneal , Humanos , Implantes Absorbibles , Stents , Procedimientos Endovasculares/métodos
13.
J Clin Endocrinol Metab ; 108(12): 3338-3344, 2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-37265226

RESUMEN

CONTEXT: The American Thyroid Association (ATA) Pediatric Guidelines recommend patients not receive radioactive iodine therapy (RAIT) for differentiated thyroid cancer (DTC) confined to the thyroid. Since publication, there is ongoing concern whether withholding RAIT will result in a lower rate of remission. OBJECTIVE: This study explores whether ATA low-risk patients treated with and without RAIT achieved similar remission rates. METHODS: Medical records of patients <19 years old diagnosed with DTC and treated with total thyroidectomy between 2010 and 2020 were reviewed. Multivariate logistic regression was performed to evaluate factors influencing RAIT administration and remission rate. RESULTS: Ninety-five patients with ATA low-risk DTC were analyzed: 53% (50/95) and 47% (45/95) were treated with and without RAIT, respectively. RAIT was used to treat 82% of patients before 2015 compared with 33% of patients after 2015 (P < .01). No significant difference in 1-year remission rate was found between patients treated with and without RAIT, 70% (35/50) vs 69% (31/45), respectively. With longer surveillance, remission rates increased to 82% and 76% for patients treated with and without RAIT, respectively. Median follow-up was 5.8 years (IQR 4.3-7.9, range 0.9-10.9) and 3.6 years (IQR 2.7-6.6; range 0.9-9.3) for both cohorts. No risk factors for persistent or indeterminate disease status were found, including RAIT administration, N1a disease, and surgery after 2015. CONCLUSION: Withholding RAIT for pediatric patients with ATA low-risk DTC avoids exposure to radiation and does not have a negative impact on remission rates. Dynamic risk stratification at 1-year after initial treatment is a suitable time point to assess the impact of withholding RAIT for these patients.


Asunto(s)
Adenocarcinoma , Neoplasias de la Tiroides , Humanos , Niño , Adulto Joven , Adulto , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Radioisótopos de Yodo/uso terapéutico , Tiroidectomía , Factores de Riesgo , Adenocarcinoma/cirugía , Estudios Retrospectivos
14.
Proteomics ; 23(20): e2300150, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37199141

RESUMEN

Blood serum is arguably the most analyzed biofluid for disease prediction and diagnosis. Herein, we benchmarked five different serum abundant protein depletion (SAPD) kits with regard to the identification of disease-specific biomarkers in human serum using bottom-up proteomics. As expected, the IgG removal efficiency among the SAPD kits is highly variable, ranging from 70% to 93%. A pairwise comparison of database search results showed a 10%-19% variation in protein identification among the kits. Immunocapturing-based SAPD kits against IgG and albumin outperformed the others in the removal of these two abundant proteins. Conversely, non-antibody-based methods (i.e., kits using ion exchange resins) and kits leveraging a multi-antibody approach were proven to be less efficient in depleting IgG/albumin from samples but led to the highest number of identified peptides. Notably, our results indicate that different cancer biomarkers could be enriched up to 10% depending on the utilized SAPD kit compared with the undepleted sample. Additionally, functional analysis of the bottom-up proteomic results revealed that different SAPD kits enrich distinct disease- and pathway-specific protein sets. Overall, our study emphasizes that a careful selection of the appropriate commercial SAPD kit is crucial for the analysis of disease biomarkers in serum by shotgun proteomics.

15.
Br J Anaesth ; 130(6): 786-794, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37055276

RESUMEN

BACKGROUND: Minimally invasive cardiac surgery provokes substantial pain and therefore analgesic consumption. The effect of fascial plane blocks on analgesic efficacy and overall patient satisfaction remains unclear. We therefore tested the primary hypothesis that fascial plane blocks improve overall benefit analgesia score (OBAS) during the initial 3 days after robotically assisted mitral valve repair. Secondarily, we tested the hypotheses that blocks reduce opioid consumption and improve respiratory mechanics. METHODS: Adults scheduled for robotically assisted mitral valve repairs were randomised to combined pectoralis II and serratus anterior plane blocks or to routine analgesia. The blocks were ultrasound-guided and used a mixture of plain and liposomal bupivacaine. OBAS was measured daily on postoperative Days 1-3 and were analysed with linear mixed effects modelling. Opioid consumption was assessed with a simple linear regression model and respiratory mechanics with a linear mixed model. RESULTS: As planned, we enrolled 194 patients, with 98 assigned to blocks and 96 to routine analgesic management. There was neither time-by-treatment interaction (P=0.67) nor treatment effect on total OBAS over postoperative Days 1-3 with a median difference of 0.08 (95% confidence interval [CI]: -0.50 to 0.67; P=0.69) and an estimated ratio of geometric means of 0.98 (95% CI: 0.85-1.13; P=0.75). There was no evidence of a treatment effect on cumulative opioid consumption or respiratory mechanics. Average pain scores on each postoperative day were similarly low in both groups. CONCLUSIONS: Serratus anterior and pectoralis plane blocks did not improve postoperative analgesia, cumulative opioid consumption, or respiratory mechanics during the initial 3 days after robotically assisted mitral valve repair. CLINICAL TRIAL REGISTRATION: NCT03743194.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Procedimientos Quirúrgicos Robotizados , Adulto , Humanos , Analgésicos Opioides , Válvula Mitral/cirugía , Analgésicos/uso terapéutico , Dolor/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/tratamiento farmacológico
16.
Front Endocrinol (Lausanne) ; 14: 1083382, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36896180

RESUMEN

DICER1 is a highly conserved RNase III endoribonuclease essential for the biogenesis of single-stranded mature microRNAs (miRNAs) from stem-loop precursor miRNAs. Somatic mutations in the RNase IIIb domain of DICER1 impair its ability to generate mature 5p miRNAs and are believed to drive tumorigenesis in DICER1 syndrome-associated and sporadic thyroid tumors. However, the DICER1-driven specific changes in miRNAs and resulting changes in gene expression are poorly understood in thyroid tissue. In this study, we profiled the miRNA (n=2,083) and mRNA (n=2,559) transcriptomes of 20 non-neoplastic, 8 adenomatous and 60 pediatric thyroid cancers (13 follicular thyroid cancers [FTC] and 47 papillary thyroid cancers [PTC]) of which 8 had DICER1 RNase IIIb mutations. All DICER1-mutant differentiated thyroid cancers (DTC) were follicular patterned (six follicular variant PTC and two FTC), none had lymph node metastasis. We demonstrate that DICER1 pathogenic somatic mutations were associated with a global reduction of 5p-derived miRNAs, including those particularly abundant in the non-neoplastic thyroid tissue such as let-7 and mir-30 families, known for their tumor suppressor function. There was also an unexpected increase of 3p miRNAs, possibly associated with DICER1 mRNA expression increase in tumors harboring RNase IIIb mutations. These abnormally expressed 3p miRNAs, which are otherwise low or absent in DICER1-wt DTC and non-neoplastic thyroid tissues, make up exceptional markers for malignant thyroid tumors harboring DICER1 RNase IIIb mutations. The extensive disarray in the miRNA transcriptome results in gene expression changes, which were indicative of positive regulation of cell-cycle. Moreover, differentially expressed genes point to increased MAPK signaling output and loss of thyroid differentiation comparable to the RAS-like subgroup of PTC (as coined by The Cancer Genome Atlas), which is reflective of the more indolent clinical behavior of these tumors.


Asunto(s)
MicroARNs , Neoplasias de la Tiroides , Niño , Humanos , ARN Helicasas DEAD-box/genética , MicroARNs/metabolismo , Mutación , Ribonucleasa III/genética , ARN Mensajero , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo
17.
Cancers (Basel) ; 15(3)2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36765847

RESUMEN

The Cancer Genome Atlas study in thyroid cancer exposed the genomic landscape of ~500 PTCs and revealed BRAFV600E-mutant tumors as having different prognosis, contrasting indolent cases and those with more invasive disease. Here, we describe the generation and characterization of six novel BRAFV600E-driven papillary thyroid cancer (PTC) cell lines established from a BrafV600E+/-/Pten+/-/TPO-Cre mouse model that spontaneously develop thyroid tumors. The novel cell lines were obtained from animals representing a range of developmental stages and both sexes, with the goal of establishing a heterogeneous panel of PTC cell lines sharing a common driver mutation. These cell lines recapitulate the genetics and diverse histopathological features of BRAFV600E-driven PTC, exhibiting differing degrees of growth, differentiation, and invasive potential that may help define mechanisms of pathogenesis underlying the heterogeneity present in the patient population. We demonstrate that these cell lines can be used for a variety of in vitro applications and can maintain the potential for in vivo transplantation into immunocompetent hosts. We believe that these novel cell lines will provide powerful tools for investigating the molecular basis of thyroid cancer progression and will lead to the development of more personalized diagnostic and treatment strategies for BRAFV600E-driven PTC.

19.
J Clin Endocrinol Metab ; 108(5): e169-e177, 2023 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-36330655

RESUMEN

CONTEXT: Pediatric thyroid cancer (TC) incidence rates are increasing, yet TC has one of the highest survival rates. Despite increased prevalence, little is known about youth adjustment to TC, particularly compared to other pediatric cancers. OBJECTIVE: The current study sought to describe health-related quality of life (HRQoL) in pediatric TC patients early after diagnosis compared to other pediatric cancer patients and healthy youth and examine predictors of HRQoL. METHODS: Pediatric TC patients (ages 8.5-23.4 years) and their caregivers from a pediatric thyroid center completed psychosocial questionnaires as part of a clinic-based screening program around time of surgery. TC HRQoL was compared to other pediatric cancer and healthy youth reported norms. Clinical and demographic data extracted from the medical record were examined for predictors of HRQoL. The main outcome measures included the Pediatric Quality of Life Inventory (PedsQL) and Distress Thermometer. RESULTS: Findings evidenced significantly higher HRQoL for TC patients than other pediatric cancers for all but emotional and school functioning. Compared to healthy youth, TC patients reported significantly lower functioning, except comparable social functioning. No significant differences in HRQoL were identified based on disease severity, thyroid disease history, or treatment. Patient distress was associated with HRQoL. CONCLUSION: The findings suggest general resilience in TC patients compared to youth with other cancers, yet worse HRQoL than peers. Early universal screening is warranted due to a short TC treatment regimen. If administrative barriers preclude comprehensive screening, the single-item Distress Thermometer may identify patients for further comprehensive screening.


Asunto(s)
Calidad de Vida , Neoplasias de la Tiroides , Adolescente , Humanos , Niño , Adulto Joven , Adulto , Calidad de Vida/psicología , Estado de Salud , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/epidemiología , Encuestas y Cuestionarios
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