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1.
Clin Cancer Res ; 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39400264

RESUMEN

BACKGROUND: DICER1-related tumor predisposition increases risk for a spectrum of benign and malignant tumors. In 2018, the International Pleuropulmonary Blastoma (PPB)/DICER1 Registry published guidelines for testing and imaging-based surveillance of individuals with a known or suspected germline DICER1 pathogenic or likely pathogenic (P/LP) variant. One of the Registry's goals is to continue to refine these guidelines as additional data becomes available. EXPERIMENTAL DESIGN: Individuals were enrolled in the International PPB/DICER1 Registry, the International Ovarian and Testicular Stromal Tumor Registry, and/or the National Cancer Institute Natural History of DICER1 Syndrome study. RESULTS: Review of participant records identified 713 participants with a germline DICER1 P/LP variant from 38 countries. To date, 5 cases of type I and 29 cases of type Ir PPB have been diagnosed by surveillance in enrolled individuals. One hundred and three individuals with a germline P/LP variant developed a primary ovarian Sertoli-Leydig cell tumor (SLCT) at a median age of 14 years (range: 11 months-66 years); 13% were diagnosed under age 8 years, the current age of onset of pelvic surveillance. Additionally, 4% of SLCTs were diagnosed before the age of 4 years. CONCLUSION: Ongoing data collection highlights the role of lung surveillance in the detection of early PPB and suggests that imaging-based detection and early resection may decrease the risk of advanced PPB. DICER1-related ovarian tumors were detected before age 8 years, prompting the Registry to recommend earlier initiation of ovarian surveillance with pelvic ultrasound beginning at the time of detection of a germline DICER1 P/LP variant.

2.
Genet Med ; : 101280, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39315526

RESUMEN

PURPOSE: Defects in the gene encoding selenocysteine insertion sequence binding protein 2, SECISBP2, result in global impaired selenoprotein synthesis manifesting a complex syndrome with characteristic serum thyroid function tests due to impaired thyroid hormone metabolism. Knowledge about this multisystemic defect remains limited. METHODS: Genetic and laboratory investigations were performed in affected members from six families presenting with short stature, failure to thrive. RESULTS: Four probands presented a complex neurodevelopmental profile, including absent speech, autistic features, and seizures. Pediatric neurological evaluation prompted genetic investigations leading to the identification of SECISBP2 variants before knowing the characteristic thyroid tests in two cases. Thyroid hormone treatment improved motor development, while speech and intellectual impairments persisted. This defect poses great diagnostic and treatment challenges for clinicians, as illustrated by a case that escaped detection for 20years, as SECISBP2 was not included in the neurodevelopmental genetic panel, and his complex thyroid status prompted anti-thyroid treatment instead. CONCLUSION: This syndrome uncovers the role of selenoproteins in humans. The severe neurodevelopmental disabilities manifested in four patients with SECISBP2 deficiency highlight an additional phenotype in this multisystem disorder. Early diagnosis and treatment are required, and long-term evaluation will determine the full spectrum of manifestations and the impact of therapy.

3.
Clin Cancer Res ; 30(20): 4566-4571, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39190470

RESUMEN

Gastrointestinal (GI) polyposis and cancer in pediatric patients is frequently due to an underlying hereditary cancer risk syndrome requiring ongoing cancer screening. Identification of at-risk patients through family history, clinical features of a syndrome, or symptom onset ensures appropriate cancer risk assessment and management in childhood and beyond. In this 2024 perspective, we outline updates to the hereditary GI cancer screening guidelines first published by the American Association of Cancer Research Pediatric Cancer Predisposition Workshop in 2017. These guidelines consider existing recommendations by pediatric and adult gastroenterology consortia to ensure alignment with gastroenterology practices in managing polyposis conditions. We specifically address the recommendations for pediatric screening in familial adenomatous polyposis, Peutz-Jeghers syndrome, and juvenile polyposis syndrome. Further, we emphasize the importance of multidisciplinary care and partnership with gastroenterology, as it is crucial in management of children and families with these conditions.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias Gastrointestinales , Predisposición Genética a la Enfermedad , Síndromes Neoplásicos Hereditarios , Humanos , Niño , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/etiología , Detección Precoz del Cáncer/métodos , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/complicaciones , Poliposis Adenomatosa del Colon/genética , Poliposis Adenomatosa del Colon/diagnóstico , Pruebas Genéticas/métodos , Guías de Práctica Clínica como Asunto , Medición de Riesgo/métodos
4.
Front Endocrinol (Lausanne) ; 15: 1443394, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39205688

RESUMEN

Objective: Levothyroxine (LT4) monotherapy is the current recommended approach for treating pediatric patients post-total thyroidectomy (TT) based on the assumption that peripheral conversion of thyroxine (T4) to triiodothyronine (T3) normalizes thyroid hormone levels. In adults, approximately 15% of post-TT patients on LT4 monotherapy have altered T4:T3 ratios with ongoing debate in regard to the clinical impact with respect to health-related quality of life (hrQOL). The ability to normalize T3 and T4 levels on LT4 monotherapy for pediatric patients' post-TT is important but not previously described. This study reports data on T3 levels in athyreotic pediatric patients to determine if a similar cohort of patients exists on LT4 monotherapy targeting normalization of TSH (LT4 replacement) or suppression (LT4 suppression). Methods: Thyroid function tests (TFTs) were retrospectively extracted from medical charts for patients <19 years old who underwent TT for definitive treatment of Graves' disease (GD) or differentiated thyroid cancer (DTC) between 2010-2021. LT4 dosing was selected to normalize the TSH in GD patients (LT4 replacement) or suppress TSH in DTC patients (LT4 suppression). Pre- and post-surgical TSH, T3 and T4 levels were compared. Results: Of 108 patients on LT4 replacement (n=53) or LT4 suppression (n=55) therapy, 94% (102/108) of patients demonstrated T3 levels in the normal range post-TT. However, the majority of patients on LT4 replacement (44/53; 83%) and LT4 suppression (31/55; 56%) displayed post-TT T3 levels in the lower half of the normal range despite 50% (22/44) and 48% (15/31) of these patients, respectively, having post-TT fT4 levels above the upper limit of the normal range. Conclusion: A significant number of pediatric patients do not achieve similar T3 and T4:T3 levels pre- and post-TT. Future multi-center, prospective studies evaluating LT4 monotherapy in comparison to combined LT4/LT3 therapy are warranted to determine the potential clinical impact of altered T3 levels in athyreotic pediatric patients.


Asunto(s)
Pruebas de Función de la Tiroides , Tiroidectomía , Tiroxina , Triyodotironina , Humanos , Tiroxina/uso terapéutico , Tiroxina/sangre , Tiroxina/administración & dosificación , Triyodotironina/sangre , Masculino , Femenino , Niño , Adolescente , Estudios Retrospectivos , Enfermedad de Graves/tratamiento farmacológico , Enfermedad de Graves/sangre , Enfermedad de Graves/cirugía , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/sangre , Neoplasias de la Tiroides/cirugía , Tirotropina/sangre , Terapia de Reemplazo de Hormonas/métodos
5.
Am J Cardiol ; 227: 48-56, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39094946

RESUMEN

Transesophageal echocardiography (TEE) plays an important role for real-time procedural guidance during surgical smyectomy (SM) for hypertrophic obstructive cardiomyopathy (HOCM). We aimed to compare (1) interventricular septum (IVS) thickness using 2- (2D) and 3-dimensional (3D) intraoperative TEE and preoperative cardiac magnetic resonance (CMR) and (2) mitral valve (MV) leaflet length using 2D, 3D TEE, automatic quantification of mitral valve (AMVQ) and preoperative CMR. We prospectively studied 50 patients with HOCM (age 59 ± 12 years, 44% men) who underwent SM during 2018 to 2019. The maximal basal, mid, and distal anteroseptum (AS) and inferoseptum (IS) were measured by multiplanar 3D reconstruction on TEE and by short-axis imaging on preoperative CMR and classified as mild (≤18 mm), moderate (18 to 25 mm), or severe (≥25 mm) groups based on AS and IS thickness on CMR. MV leaflet lengths were evaluated by preoperative CMR and intraprocedural 2D TEE, zoom 3D TEE, and AMVQ (EchoPAC, General Electric, Wisconsin). There was a moderate correlation between AS and IS thickness on 3D TEE and CMR (R2 = 0.46, p <0.01 and R2 = 0.41, p <0.01, respectively), with 3D TEE showing an average overestimation of 3.8 and 4.7 mm versus CMR. The 3D TEE overestimated 14 patients (56%) with mild thickness as moderate and 5 patients (22%) with moderate thickness as severe. Assuming 3D TEE as the gold standard, the closest correlation for anterior mitral leaflet length was with CMR (average overestimation by CMR of 0.5 mm [root mean square deviation (RMSE%) 17]), intermediate correlation with 2D TEE (average deviation of 0.6 mm [RMSE% 21]) and no correlation with AMVQ (average deviation of 0.7 mm [RMSE% 24]). In conclusion, 3D TEE overestimates IVS thickness versus CMR in patients with HOCM who underwent SM, with greater discrepancy in those with thinner IVS. There are significant differences in MV lengths measured using different imaging techniques.


Asunto(s)
Cardiomiopatía Hipertrófica , Ecocardiografía Tridimensional , Ecocardiografía Transesofágica , Válvula Mitral , Imagen Multimodal , Tabique Interventricular , Humanos , Cardiomiopatía Hipertrófica/cirugía , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Persona de Mediana Edad , Masculino , Femenino , Estudios Prospectivos , Tabique Interventricular/diagnóstico por imagen , Tabique Interventricular/cirugía , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Ecocardiografía Transesofágica/métodos , Ecocardiografía Tridimensional/métodos , Anciano , Imagen por Resonancia Cinemagnética/métodos , Procedimientos Quirúrgicos Cardíacos/métodos , Imagen por Resonancia Magnética/métodos
6.
Front Pediatr ; 12: 1444919, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39132310

RESUMEN

Monocarboxylate transporter 8 (MCT8) deficiency is a rare, X-linked disorder arising from mutations in the SLC16A2 gene and resulting from dysfunctional thyroid hormone transport. This disorder is characterized by profound neurodevelopmental delay and motor disability due to a lack of thyroid hormone in the brain, and coexisting endocrinological symptoms, due to chronic thyrotoxicosis, resulting from elevated thyroid hormone outside the central nervous system (CNS). In February 2024, we reviewed the published literature to identify relevant articles reporting on the current unmet needs of patients with MCT8 deficiency. There are several main challenges in the diagnosis and treatment of MCT8 deficiency, with decreased awareness and recognition of MCT8 deficiency among healthcare professionals (HCPs) associated with misdiagnosis and delays in diagnosis. Diagnostic delay may also be attributed to other factors, including the complex symptomology of MCT8 deficiency only becoming apparent several months after birth and pathognomonic serum triiodothyronine (T3) testing not being routinely performed. For patients with MCT8 deficiency, multidisciplinary team care is vital to optimize the support provided to patients and their caregivers. Although there are currently no approved treatments specifically for MCT8 deficiency, earlier identification and diagnosis of this disorder enables earlier access to supportive care and developing treatments focused on improving outcomes and quality of life for both patients and caregivers.

7.
Thyroid ; 34(10): 1308-1313, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39104254

RESUMEN

Background: Receptor tyrosine kinase (RTK) fusions of RET, NTRK1/3, and ALK are enriched among pediatric thyroid cancer patients with metastatic and persistent disease, and their oncoproteins represent attractive drug targets. Methods: We performed RNA-sequencing in a papillary thyroid cancer (PTC) lacking other frequent driver alterations. Results: We report a novel RTK fusion, TG-insulin-like growth factor 1 receptor gene (IGF1R), in a 17-year-old female patient with angioinvasive follicular variant PTC. The in-frame fusion protein preserves the cholinesterase-like domain of TG with dimerization properties and the transmembrane and kinase domain of IGF1R. The tumor sample shows increased IGF1R mRNA expression and tyrosine kinase phosphorylation, augmentation of Mitogen activated protein kinase (MAPK) transcriptional output genes, and decreased NIS levels. Conclusions: We reveal a novel targetable kinase fusion oncogene in thyroid cancer which is not incorporated in different thyroid-specific sequencing panels. The integration of IGF1R fusion screening in the next versions of thyroid-specific targeted next-generation sequencing panels may be beneficial to thyroid cancer patients.


Asunto(s)
Proteínas de Fusión Oncogénica , Receptor IGF Tipo 1 , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Femenino , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Adolescente , Receptor IGF Tipo 1/genética , Proteínas de Fusión Oncogénica/genética , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología
8.
Alzheimers Dement ; 20(8): 5590-5606, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38958537

RESUMEN

INTRODUCTION: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention. METHODS: Patients with MCI and age-matched controls (CN) were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry. RESULTS: Neurovascular coupling (NVC) and functional connectivity (FC) were decreased in MCI compared to CN, prominently in the left-dorsolateral prefrontal cortex (LDLPFC). We observed an increased ratio of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared to CN, correlating with structural MRI small vessel ischemic damage in MCI. LDLPFC NVC, CEEV ratio, and LDLPFC FC had the highest feature importance in the random Forest group classification. DISCUSSION: NVC, CEEVs, and FC predict MCI diagnosis, indicating their potential as markers for MCI cerebrovascular pathology. HIGHLIGHTS: Neurovascular coupling (NVC) is impaired in mild cognitive impairment (MCI). Functional connectivity (FC) compensation mechanism is lost in MCI. Cerebrovascular endothelial extracellular vesicles (CEEVs) are increased in MCI. CEEV load strongly associates with cerebral small vessel ischemic lesions in MCI. NVC, CEEVs, and FC predict MCI diagnosis over demographic and comorbidity factors.


Asunto(s)
Biomarcadores , Disfunción Cognitiva , Vesículas Extracelulares , Acoplamiento Neurovascular , Humanos , Disfunción Cognitiva/fisiopatología , Vesículas Extracelulares/metabolismo , Femenino , Masculino , Anciano , Biomarcadores/sangre , Acoplamiento Neurovascular/fisiología , Imagen por Resonancia Magnética , Espectroscopía Infrarroja Corta , Persona de Mediana Edad
9.
Eur Thyroid J ; 13(4)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38984999

RESUMEN

Objective: The American Thyroid Association (ATA) Pediatric Guidelines recommend selective, prophylactic central neck dissection (pCND) for patients with papillary thyroid carcinoma (PTC) based on tumor focality, tumor size, and the surgeon's experience. With the expansion of pre-surgical somatic oncogene testing and continued controversy over the benefits of pCND, oncogenic alteration data may provide an opportunity to stratify pCND. This study compared lymph node (LN) involvement in pediatric patients with PTC between tumors with low- and high-invasive-associated alterations to explore the potential utility of preoperative oncogenic alterations in the stratification of pCND. Methods: This is retrospective cohort study of pediatric patients who underwent somatic oncogene testing post thyroidectomy for PTC between July 2003 and July 2022. Results: Of 192 eligible PTC patients with postoperative somatic oncogene data, 19 tumors harbored somatic alterations associated with low-invasive disease (19/192, 10%), and 128 tumors harbored a BRAFV600E alteration (45/192, 23%) or an oncogenic fusion (83/192, 43%). Tumors with low-invasive alterations were less likely to present malignant preoperative cytology (2/18, 11%) than those with high-invasive alterations (97/124, 78%; P < 0.001). Twelve patients with low-invasive alterations had LNs dissected from the central neck (12/19, 63%) compared to 127 patients (127/128, 99%) with high-invasive alterations. LN metastasis was identified in two patients with low-invasive alterations (2/19, 11%) compared to 107 patients with high-invasive alterations (107/128, 84%; P < 0.001). Conclusion: Pediatric patients with low-invasive somatic oncogenic alterations are at low risk for metastasis to central neck LNs. Our findings suggest that preoperative knowledge of somatic oncogene alterations provides objective data to stratify pediatric patients who may not benefit from pCND.


Asunto(s)
Metástasis Linfática , Disección del Cuello , Oncogenes , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/cirugía , Cáncer Papilar Tiroideo/patología , Masculino , Niño , Femenino , Estudios Retrospectivos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Adolescente , Metástasis Linfática/patología , Metástasis Linfática/genética , Oncogenes/genética , Tiroidectomía , Proteínas Proto-Oncogénicas B-raf/genética , Preescolar
10.
J Clin Anesth ; 97: 111550, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39029153

RESUMEN

BACKGROUND: Minimally invasive thoracic surgery is associated with substantial pain that can impair pulmonary function. Fascial plane blocks may offer a favorable alternative to opioids, but conventional local anesthetics provide a limited duration of analgesia. We therefore tested the primary hypothesis that a mixture of liposomal bupivacaine and plain bupivacaine improves the overall benefit of analgesia score (OBAS) during the first three postoperative days compared to bupivacaine alone. Secondarily, we tested the hypotheses that liposomal bupivacaine improves respiratory mechanics, and decreases opioid consumption. METHODS: Adults scheduled for robotically or video-assisted thoracic surgery with combined ultrasound-guided pectoralis II and serratus anterior plane block were randomized to bupivacaine or bupivacaine combined with liposomal bupivacaine. OBAS was measured on postoperative days 1-3 and was analyzed with a linear mixed regression model. Postoperative respiratory mechanics were estimated using a linear mixed model. Total opioid consumption was estimated with a simple linear regression model. RESULTS: We analyzed 189 patients, of whom 95 were randomized to the treatment group and 94 to the control group. There was no significant treatment effect on total OBAS during the initial three postoperative days, with an estimated geometric mean ratio of 0.93 (95% CI: 0.76, 1.14; p = 0.485). There was no observed treatment effect on respiratory mechanics, total opioid consumption, or pain scores. Average pain scores were low in both groups. CONCLUSIONS: Liposomal bupivacaine did not improve OBAS during the initial postoperative three days following minimally invasive thoracic procedures. Furthermore, there was no improvement in respiratory mechanics, no reduction in opioid consumption, and no decrease in pain scores. Thus, the data presented here does not support the use of liposomal bupivacaine over standard bupivacaine to enhance analgesia after minimally invasive thoracic surgery. SUMMARY STATEMENT: For minimally invasive thoracic procedures, addition of liposomal bupivacaine to plain bupivacaine for thoracic fascial plane blocks does not improve OBAS, reduce opioid requirements, improve postoperative respiratory mechanics, or decrease pain scores.


Asunto(s)
Analgésicos Opioides , Anestésicos Locales , Bupivacaína , Liposomas , Procedimientos Quirúrgicos Mínimamente Invasivos , Bloqueo Nervioso , Dolor Postoperatorio , Humanos , Bupivacaína/administración & dosificación , Anestésicos Locales/administración & dosificación , Masculino , Femenino , Bloqueo Nervioso/métodos , Persona de Mediana Edad , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/etiología , Liposomas/administración & dosificación , Anciano , Analgésicos Opioides/administración & dosificación , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Ultrasonografía Intervencional , Dimensión del Dolor , Músculos Pectorales/efectos de los fármacos , Músculos Pectorales/inervación , Cirugía Torácica Asistida por Video/métodos , Cirugía Torácica Asistida por Video/efectos adversos , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Adulto , Mecánica Respiratoria/efectos de los fármacos , Procedimientos Quirúrgicos Torácicos/efectos adversos , Procedimientos Quirúrgicos Torácicos/métodos
11.
Front Neurol ; 15: 1398876, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38915798

RESUMEN

Background: Arteriovenous malformations (AVMs) are rare vascular anomalies involving a disorganization of arteries and veins with no intervening capillaries. In the past 10 years, radiomics and machine learning (ML) models became increasingly popular for analyzing diagnostic medical images. The goal of this review was to provide a comprehensive summary of current radiomic models being employed for the diagnostic, therapeutic, prognostic, and predictive outcomes in AVM management. Methods: A systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, in which the PubMed and Embase databases were searched using the following terms: (cerebral OR brain OR intracranial OR central nervous system OR spine OR spinal) AND (AVM OR arteriovenous malformation OR arteriovenous malformations) AND (radiomics OR radiogenomics OR machine learning OR artificial intelligence OR deep learning OR computer-aided detection OR computer-aided prediction OR computer-aided treatment decision). A radiomics quality score (RQS) was calculated for all included studies. Results: Thirteen studies were included, which were all retrospective in nature. Three studies (23%) dealt with AVM diagnosis and grading, 1 study (8%) gauged treatment response, 8 (62%) predicted outcomes, and the last one (8%) addressed prognosis. No radiomics model had undergone external validation. The mean RQS was 15.92 (range: 10-18). Conclusion: We demonstrated that radiomics is currently being studied in different facets of AVM management. While not ready for clinical use, radiomics is a rapidly emerging field expected to play a significant future role in medical imaging. More prospective studies are warranted to determine the role of radiomics in the diagnosis, prediction of comorbidities, and treatment selection in AVM management.

12.
J Neurol Surg Rep ; 85(2): e88-e95, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38881626

RESUMEN

Background The ability to participate in clinical scholarship is a foundational component of modern evidence-based medical practice, empowering improvement across essentially every aspect of clinical care. In tandem, the need for comprehensive exposure to clinical research has been identified as a critical component of medical student training and preparation for residency that is underserved by traditional undergraduate medical education models. The goal of the current work was to provide guidelines and recommendations to assist novice medical students in taking ownership of their research education. Methods The Clinical Research Primer was composed from pooled research documents compiled by the study authors and our institutional neurosurgery student research group. The Primer was then structured as the natural evolution of a research project from its inception through the submission process. Results We divided the foundational components of the Clinical Research Primer into seven domains, each representing a landmark in the development of a peer-reviewed study, and a set of skills critical for junior scholars to develop. These vital components included the following: pitching and designing clinical studies, developing a research workflow, navigating the Institutional Review Board, data collection and analysis, manuscript writing and editing, submission mechanics, and tracking research projects for career development. Conclusion We anticipate that the tools included in the Clinical Research Primer will increase student research productivity and preparedness for residency. Although our recommendations are informed by our experiences within neurosurgery, they have been written in a manner that should generalize to almost any field of clinical study.

13.
World Neurosurg ; 188: 99-110, 2024 Aug.
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 neurologic 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 neurologic dysfunction; data regarding adjuvant chemoradiation are less consistently reported, mandating further study.


Asunto(s)
Hemangioendotelioma Epitelioide , Procedimientos Neuroquirúrgicos , Adulto , Humanos , Masculino , Descompresión Quirúrgica/métodos , Hemangioendotelioma Epitelioide/cirugía , Hemangioendotelioma Epitelioide/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Procedimientos Neuroquirúrgicos/métodos , Neoplasias de la Médula Espinal/cirugía , Neoplasias de la Médula Espinal/diagnóstico por imagen , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Vértebras Torácicas/cirugía
14.
J Clin Neurosci ; 125: 106-109, 2024 Jul.
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.


Asunto(s)
Hemorragia Subaracnoidea Traumática , Vasoespasmo Intracraneal , Humanos , Vasoespasmo Intracraneal/epidemiología , Vasoespasmo Intracraneal/etiología , Vasoespasmo Intracraneal/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Hemorragia Subaracnoidea Traumática/diagnóstico por imagen , Hemorragia Subaracnoidea Traumática/complicaciones , Hemorragia Subaracnoidea Traumática/epidemiología , Adulto , Anciano , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/epidemiología , Incidencia , Tomografía Computarizada por Rayos X , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/epidemiología , Hemorragia Subaracnoidea/diagnóstico por imagen
15.
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.

16.
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
17.
J Am Soc Echocardiogr ; 37(6): 626-633, 2024 Jun.
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.


Asunto(s)
Válvula Aórtica , Ecocardiografía Tridimensional , Humanos , Ecocardiografía Tridimensional/métodos , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Hemodinámica/fisiología , Atención Perioperativa/métodos , Aorta/diagnóstico por imagen , Aorta/cirugía
18.
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.

19.
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.

20.
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
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