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1.
Front Oncol ; 14: 1425545, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39211550

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally. Notably, human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is on the rise, accounting for 70% of all OPSCC cases. Persistent high-risk HPV infection is linked to various cancers, but HPV infection alone is not sufficient to cause cancer. Advances in next-generation sequencing have improved our understanding of changes in the human microbiome of cancerous environments. Yet, there remains a dearth of knowledge on the impact of HPV-microbiome crosstalk in HPV-positive OPSCC. In this review, we examine what is known about the oropharyngeal microbiome and the compositional shifts in this microbiome in HPV-positive OPSCC. We also review potential mechanisms of crosstalk between HPV and specific microorganisms. Additional research is needed to understand these interactions and their roles on cancer development and progression.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39115834

RESUMO

Importance: Cannabis is the most commonly used illicit substance worldwide. Whether cannabis use is associated with head and neck cancer (HNC) is unclear. Objective: To assess the clinical association between cannabis use and HNC. Design, Setting, and Participants: This large multicenter cohort study used clinical records from a database that included 20 years of data (through April 2024) from 64 health care organizations. A database was searched for medical records for US adults with and without cannabis-related disorder who had recorded outpatient hospital clinic visits and no prior history of HNC. Propensity score matching was performed for demographic characteristics, alcohol-related disorders, and tobacco use. Subsequently, relative risks (RRs) were calculated to explore risk of HNC, including HNC subsites. This analysis was repeated among those younger than 60 years and 60 years or older. Exposure: Cannabis-related disorder. Main Outcomes and Measures: Diagnosis of HNC and any HNC subsite. Results: The cannabis-related disorder cohort included 116 076 individuals (51 646 women [44.5%]) with a mean (SD) age of 46.4 (16.8) years. The non-cannabis-related disorder cohort included 3 985 286 individuals (2 173 684 women [54.5%]) with a mean (SD) age of 60.8 (20.6) years. The rate of new HNC diagnosis in all sites was higher in the cannabis-related disorder cohort. After matching (n = 115 865 per group), patients with cannabis-related disorder had a higher risk of any HNC (RR, 3.49; 95% CI, 2.78-4.39) than those without HNC. A site-specific analysis yielded that those with cannabis-related disorder had a higher risk of oral (RR, 2.51; 95% CI, 1.81-3.47), oropharyngeal (RR, 4.90; 95% CI, 2.99-8.02), and laryngeal (RR, 8.39; 95% CI, 4.72-14.90) cancer. Results were consistent when stratifying by older and younger age group. Conclusions and Relevance: This cohort study highlights an association between cannabis-related disorder and the development of HNC in adult patients. Given the limitations of the database, future research should examine the mechanism of this association and analyze dose response with strong controls to further support evidence of cannabis use as a risk factor for HNCs.

3.
Oper Neurosurg (Hagerstown) ; 27(3): 265-278, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38869495

RESUMO

BACKGROUND AND OBJECTIVES: Suprasellar tumors, particularly pituitary adenomas (PAs), commonly present with visual decline, and the endoscopic endonasal transsphenoidal approach (EETA) is the primary management for optic apparatus decompression. Patients presenting with complete preoperative monocular blindness comprise a high-risk subgroup, given concern for complete blindness. This retrospective cohort study evaluates outcomes after EETA for patients with PA presenting with monocular blindness. METHODS: Retrospective analysis of all EETA cases at our institution from June 2012 to August 2023 was performed. Inclusion criteria included adults with confirmed PA and complete monocular blindness, defined as no light perception, and a relative afferent pupillary defect secondary to tumor mass effect. RESULTS: Our cohort includes 15 patients (9 males, 6 females), comprising 2.4% of the overall PA cohort screened. The mean tumor diameter was 3.8 cm, with 6 being giant PAs (>4 cm). The mean duration of preoperative monocular blindness was 568 days. Additional symptoms included contralateral visual field defects (n = 11) and headaches (n = 10). Two patients presented with subacute PA apoplexy. Gross total resection was achieved in 46% of patients, reflecting tumor size and invasiveness. Postoperatively, 2 patients experienced improvement in their effectively blind eye and 2 had improved visual fields of the contralateral eye. Those with improvements were operated within 10 days of presentation, and no patients experienced worsened vision. CONCLUSION: This is the first series of EETA outcomes in patients with higher-risk PA with monocular blindness on presentation. In these extensive lesions, vision remained stable for most without further decline and improvement from monocular blindness was observed in a small subset of patients with no light perception and relative afferent pupillary defect. Timing from vision loss to surgical intervention seemed to be associated with improvement. From a surgical perspective, caution is warranted to protect remaining vision and we conclude that EETA is safe in the management of these patients.


Assuntos
Adenoma , Cegueira , Neoplasias Hipofisárias , Humanos , Masculino , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/diagnóstico por imagem , Feminino , Cegueira/etiologia , Cegueira/cirurgia , Pessoa de Meia-Idade , Adenoma/cirurgia , Adenoma/complicações , Estudos Retrospectivos , Adulto , Idoso , Neuroendoscopia/métodos , Resultado do Tratamento , Cirurgia Endoscópica por Orifício Natural/métodos
4.
J Comput Assist Tomogr ; 48(4): 614-627, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38626756

RESUMO

ABSTRACT: Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions. It categorizes tumors based on their locations: gastric, duodenal, pancreatic, small bowel, colonic, rectal, appendiceal, gallbladder, prostate, lung, gynecological, and others. The piece also elucidates the challenges in managing metastatic disease and controversies surrounding MEN1-neuroendocrine tumor management. The article underscores the significance of individualized treatment plans, underscoring the need for a multidisciplinary approach to ensure optimal patient outcomes.


Assuntos
Tumores Neuroendócrinos , Humanos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/patologia
5.
AJR Am J Roentgenol ; 222(5): e2330720, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38353447

RESUMO

BACKGROUND. The 2022 Society of Radiologists in Ultrasound (SRU) consensus conference recommendations for small gallbladder polyps support management that is less aggressive than earlier approaches and may help standardize evaluation of polyps by radiologists. OBJECTIVE. The purpose of the present study was to assess the interreader agreement of radiologists in applying SRU recommendations for management of incidental gallbladder polyps on ultrasound. METHODS. This retrospective study included 105 patients (75 women and 30 men; median age, 51 years) with a gallbladder polyp on ultrasound (without features highly suspicious for invasive or malignant tumor) who underwent cholecystectomy between January 1, 2003, and January 1, 2021. Ten abdominal radiologists independently reviewed ultrasound examinations and, using the SRU recommendations, assessed one polyp per patient to assign risk category (extremely low risk, low risk, or indeterminate risk) and make a possible recommendation for surgical consultation. Five radiologists were considered less experienced (< 5 years of experience), and five were considered more experienced (≥ 5 years of experience). Interreader agreement was evaluated. Polyps were classified pathologically as nonneoplastic or neoplastic. RESULTS. For risk category assignments, interreader agreement was substantial among all readers (k = 0.710), less-experienced readers (k = 0.705), and more-experienced readers (k = 0.692). For surgical consultation recommendations, inter-reader agreement was substantial among all readers (k = 0.795) and more-experienced readers (k = 0.740) and was almost perfect among less-experienced readers (k = 0.811). Of 10 readers, a median of 5.0 (IQR, 2.0-8.0), 4.0 (IQR, 2.0-7.0), and 0.0 (IQR, 0.0-0.0) readers classified polyps as extremely low risk, low risk, and indeterminate risk, respectively. Across readers, the percentage of polyps classified as extremely low risk ranged from 32% to 72%; as low risk, from 24% to 65%; and as indeterminate risk, from 0% to 8%. Of 10 readers, a median of zero change to 0 (IQR, 0.0-1.0) readers recommended surgical consultation; the percentage of polyps receiving a recommendation for surgical consultation ranged from 4% to 22%. Of a total of 105 polyps, 102 were nonneo-plastic and three were neoplastic (all benign). Based on readers' most common assessments for nonneoplastic polyps, the risk category was extremely low risk for 53 polyps, low risk for 48 polyps, and indeterminate risk for one polyp; surgical consultation was recommended for 16 polyps. CONCLUSION. Ten abdominal radiologists showed substantial agreement for polyp risk categorizations and surgical consultation recommendations, although areas of reader variability were identified. CLINICAL IMPACT. The findings support the overall reproducibility of the SRU recommendations, while indicating opportunity for improvement.


Assuntos
Achados Incidentais , Pólipos , Ultrassonografia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Pólipos/diagnóstico por imagem , Pólipos/cirurgia , Estudos Retrospectivos , Ultrassonografia/métodos , Adulto , Doenças da Vesícula Biliar/diagnóstico por imagem , Doenças da Vesícula Biliar/cirurgia , Idoso , Variações Dependentes do Observador , Radiologistas , Sociedades Médicas , Consenso , Guias de Prática Clínica como Assunto
6.
Trials ; 24(1): 512, 2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563721

RESUMO

BACKGROUND: Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors. METHODS: STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site ("cluster") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions. DISCUSSION: The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency. TRIAL REGISTRATION: ISRCTN: 10412338. Registration date: October 24, 2019.


Assuntos
Doadores de Sangue , Síncope Vasovagal , Humanos , Medicina Estatal , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/etiologia , Síncope Vasovagal/prevenção & controle , Água , Doação de Sangue
7.
Radiographics ; 43(7): e220191, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37347698

RESUMO

The radiologic diagnosis of adrenal disease can be challenging in settings of atypical presentations, mimics of benign and malignant adrenal masses, and rare adrenal anomalies. Misdiagnosis may lead to suboptimal management and adverse outcomes. Adrenal adenoma is the most common benign adrenal tumor that arises from the cortex, whereas adrenocortical carcinoma (ACC) is a rare malignant tumor of the cortex. Adrenal cyst and myelolipoma are other benign adrenal lesions and are characterized by their fluid and fat content, respectively. Pheochromocytoma is a rare neuroendocrine tumor of the adrenal medulla. Metastases to the adrenal glands are the most common malignant adrenal tumors. While many of these masses have classic imaging appearances, considerable overlap exists between benign and malignant lesions and can pose a diagnostic challenge. Atypical adrenal adenomas include those that are lipid poor; contain macroscopic fat, hemorrhage, and/or iron; are heterogeneous and/or large; and demonstrate growth. Heterogeneous adrenal adenomas may mimic ACC, metastasis, or pheochromocytoma, particularly when they are 4 cm or larger, whereas smaller versions of ACC, metastasis, and pheochromocytoma and those with washout greater than 60% may mimic adenoma. Because of its nonenhanced CT attenuation of less than or equal to 10 HU, a lipid-rich adrenal adenoma may be mimicked by a benign adrenal cyst, or it may be mimicked by a tumor with central cystic and/or necrotic change such as ACC, pheochromocytoma, or metastasis. Rare adrenal tumors such as hemangioma, ganglioneuroma, and oncocytoma also may mimic adrenal adenoma, ACC, metastasis, and pheochromocytoma. The authors describe cases of adrenal neoplasms that they have encountered in clinical practice and presented to adrenal multidisciplinary tumor boards. Key lessons to aid in diagnosis and further guide appropriate management are provided. © RSNA, 2023 Online supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.


Assuntos
Adenoma , Neoplasias do Córtex Suprarrenal , Neoplasias das Glândulas Suprarrenais , Carcinoma Adrenocortical , Cistos , Feocromocitoma , Humanos , Feocromocitoma/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Carcinoma Adrenocortical/diagnóstico por imagem , Cistos/patologia , Lipídeos
8.
JAMA Surg ; 158(7): e231112, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37133836

RESUMO

Importance: Intravenous (IV) contrast medium is sometimes withheld due to risk of complication or lack of availability in patients undergoing computed tomography (CT) for abdominal pain. The risk from withholding contrast medium is understudied. Objective: To determine the diagnostic accuracy of unenhanced abdominopelvic CT using contemporaneous contrast-enhanced CT as the reference standard in emergency department (ED) patients with acute abdominal pain. Design, Setting, and Participants: This was an institutional review board-approved, multicenter retrospective diagnostic accuracy study of 201 consecutive adult ED patients who underwent dual-energy contrast-enhanced CT for the evaluation of acute abdominal pain from April 1, 2017, through April 22, 2017. Three blinded radiologists interpreted these scans to establish the reference standard by majority rule. IV and oral contrast media were then digitally subtracted using dual-energy techniques. Six different blinded radiologists from 3 institutions (3 specialist faculty and 3 residents) interpreted the resulting unenhanced CT examinations. Participants included a consecutive sample of ED patients with abdominal pain who underwent dual-energy CT. Exposure: Contrast-enhanced and virtual unenhanced CT derived from dual-energy CT. Main outcome: Diagnostic accuracy of unenhanced CT for primary (ie, principal cause[s] of pain) and actionable secondary (ie, incidental findings requiring management) diagnoses. The Gwet interrater agreement coefficient was calculated. Results: There were 201 included patients (female, 108; male, 93) with a mean age of 50.1 (SD, 20.9) years and mean BMI of 25.5 (SD, 5.4). Overall accuracy of unenhanced CT was 70% (faculty, 68% to 74%; residents, 69% to 70%). Faculty had higher accuracy than residents for primary diagnoses (82% vs 76%; adjusted odds ratio [OR], 1.83; 95% CI, 1.26-2.67; P = .002) but lower accuracy for actionable secondary diagnoses (87% vs 90%; OR, 0.57; 95% CI, 0.35-0.93; P < .001). This was because faculty made fewer false-negative primary diagnoses (38% vs 62%; OR, 0.23; 95% CI, 0.13-0.41; P < .001) but more false-positive actionable secondary diagnoses (63% vs 37%; OR, 2.11, 95% CI, 1.26-3.54; P = .01). False-negative (19%) and false-positive (14%) results were common. Interrater agreement for overall accuracy was moderate (Gwet agreement coefficient, 0.58). Conclusion: Unenhanced CT was approximately 30% less accurate than contrast-enhanced CT for evaluating abdominal pain in the ED. This should be balanced with the risk of administering contrast material to patients with risk factors for kidney injury or hypersensitivity reaction.


Assuntos
Abdome Agudo , Tomografia Computadorizada por Raios X , Adulto , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Dor Abdominal/diagnóstico por imagem , Dor Abdominal/etiologia , Serviço Hospitalar de Emergência
9.
Clin Neurophysiol ; 152: 93-111, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37208270

RESUMO

Neurostimulation has diverse clinical applications and potential as a treatment for medically refractory movement disorders, epilepsy, and other neurological disorders. However, the parameters used to program electrodes-polarity, pulse width, amplitude, and frequency-and how they are adjusted have remained largely untouched since the 1970 s. This review summarizes the state-of-the-art in Deep Brain Stimulation (DBS) and highlights the need for further research to uncover the physiological mechanisms of neurostimulation. We focus on studies that reveal the potential for clinicians to use waveform parameters to selectively stimulate neural tissue for therapeutic benefit, while avoiding activating tissue associated with adverse effects. DBS uses cathodic monophasic rectangular pulses with passive recharging in clinical practice to treat neurological conditions such as Parkinson's Disease. However, research has shown that stimulation efficiency can be improved, and side effects reduced, through modulating parameters and adding novel waveform properties. These developments can prolong implantable pulse generator lifespan, reducing costs and surgery-associated risks. Waveform parameters can stimulate neurons based on axon orientation and intrinsic structural properties, providing clinicians with more precise targeting of neural pathways. These findings could expand the spectrum of diseases treatable with neuromodulation and improve patient outcomes.


Assuntos
Estimulação Encefálica Profunda , Doenças do Sistema Nervoso , Doença de Parkinson , Humanos , Estimulação Encefálica Profunda/efeitos adversos , Eletrodos , Neurofisiologia
10.
Acad Radiol ; 30(7): 1340-1349, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36216684

RESUMO

RATIONALE AND OBJECTIVES: To evaluate whether addition of a computer-aided diagnostic (CAD) generated MRI series improves detection of clinically significant prostate cancer. MATERIALS AND METHODS: Nine radiologists retrospectively interpreted 150 prostate MRI examinations without and then with an additional random forest-based CAD model-generated MRI series. Characteristics of biopsy negative versus positive (Gleason ≥ 7 adenocarcinoma) groups were compared using the Wilcoxon test for continuous and Pearson's chi-squared test for categorical variables. The diagnostic performance of readers was compared without versus with CAD using MRMC methods to estimate the area under the receiver operator characteristic curve (AUC). Inter-reader agreement was assessed using weighted inter-rater agreement statistics. Analyses were repeated in peripheral and transition zone subgroups. RESULTS: Among 150 men with median age 67 ± 7.4 years, those with clinically significant prostate cancer were older (68 ± 7.6 years vs. 66 ± 7.0 years; p < .02), had smaller prostate volume (43.9 mL vs. 60.6 mL; p < .001), and no difference in prostate specific antigen (PSA) levels (7.8 ng/mL vs. 6.9 ng/mL; p = .08), but higher PSA density (0.17 ng/mL/cc vs. 0.10 ng/mL/cc; p < .001). Inter-rater agreement (IRA) for PI-RADS scores was moderate without CAD and significantly improved to substantial with CAD (IRA = 0.47 vs. 0.65; p < .001). CAD also significantly improved average reader AUC (AUC = 0.72, vs. AUC = 0.67; p = .02). CONCLUSION: Addition of a random forest method-based, CAD-generated MRI image series improved inter-reader agreement and diagnostic performance for detection of clinically significant prostate cancer, particularly in the transition zone.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Neoplasias da Próstata/diagnóstico por imagem , Imageamento por Ressonância Magnética , Antígeno Prostático Específico , Estudos Retrospectivos , Computadores
11.
AJR Am J Roentgenol ; 220(1): 86-94, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35920707

RESUMO

BACKGROUND. Homogeneous microscopic fat within adrenal nodules on chemical-shift MRI (CS-MRI) is diagnostic of benign adrenal adenoma, but the clinical relevance of heterogeneous microscopic fat is not well established. OBJECTIVE. This study sought to determine the prevalence of malignancy in adrenal nodules with heterogeneous microscopic fat on dual-echo T1-weighted CS-MRI. METHODS. We performed a retrospective study of adult patients with adrenal nodules detected on MRI performed between August 2007 and November 2020 at seven institutions. Eligible nodules had a short-axis diameter of 10 mm or larger with heterogeneous microscopic fat (defined by an area of signal loss of < 80% on opposed-phase CS-MRI). Two radiologists from each center, blinded to reference standard results, determined the signal loss pattern (diffuse, two distinct parts, speckling pattern, central loss, or peripheral loss) within the nodules. The reference standard used was available for 283 nodules (pathology for 21 nodules, ≥ 1 year of imaging follow-up for 245, and ≥ 5 years of clinical follow-up for 17) in 282 patients (171 women and 111 men; mean age, 60 ± 12 [SD] years); 30% (86/282) patients had prior malignancy. RESULTS. The mean long-axis diameter was 18.7 ± 7.9 mm (range, 10-80 mm). No malignant nodules were found in patients without prior cancer (0/197; 95% CI, 0-1.5%). Four of the 86 patients with prior malignancy (hepatocellular carcinoma [HCC], renal cell carcinoma [RCC], lung cancer, or both colon cancer and RCC) (4.7%; 95% CI, 1.3-11.5%) had metastatic nodules. Detected patterns were diffuse heterogeneous signal loss (40% [114/283]), speckling (28% [80/283]), two distinct parts (18% [51/283]), central loss (9% [26/283]), and peripheral loss (4% [12/283]). Two metastases from HCC and RCC showed diffuse heterogeneous signal loss. Lung cancer metastasis manifested as two distinct parts, and the metastasis in the patient with both colon cancer and RCC showed peripheral signal loss. CONCLUSION. Presence of heterogeneous microscopic fat in adrenal nodules on CS-MRI indicates a high likelihood of benignancy, particularly in patients without prior cancer. This finding is also commonly benign in patients with cancer; however, caution is warranted when primary malignancies may contain fat or if the morphologic pattern of signal loss may indicate a collision tumor. CLINICAL IMPACT. In the absence of prior cancer, adrenal nodules with heterogeneous microscopic fat do not require additional imaging evaluation.


Assuntos
Neoplasias das Glândulas Suprarrenais , Carcinoma Hepatocelular , Carcinoma de Células Renais , Neoplasias do Colo , Neoplasias Renais , Neoplasias Hepáticas , Neoplasias Pulmonares , Adulto , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Carcinoma de Células Renais/patologia , Estudos Retrospectivos , Prevalência , Imageamento por Ressonância Magnética/métodos , Diagnóstico Diferencial , Neoplasias Renais/patologia , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem
12.
Nat Commun ; 13(1): 5803, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36192477

RESUMO

Age is the primary risk factor for many common human diseases. Here, we quantify the relative contributions of genetics and aging to gene expression patterns across 27 tissues from 948 humans. We show that the predictive power of expression quantitative trait loci is impacted by age in many tissues. Jointly modelling the contributions of age and genetics to transcript level variation we find expression heritability (h2) is consistent among tissues while the contribution of aging varies by >20-fold with [Formula: see text] in 5 tissues. We find that while the force of purifying selection is stronger on genes expressed early versus late in life (Medawar's hypothesis), several highly proliferative tissues exhibit the opposite pattern. These non-Medawarian tissues exhibit high rates of cancer and age-of-expression-associated somatic mutations. In contrast, genes under genetic control are under relaxed constraint. Together, we demonstrate the distinct roles of aging and genetics on expression phenotypes.


Assuntos
Envelhecimento , Locos de Características Quantitativas , Envelhecimento/genética , Expressão Gênica , Regulação da Expressão Gênica , Humanos , Fenótipo , Locos de Características Quantitativas/genética
13.
AJR Am J Roentgenol ; 219(1): 97-109, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35080458

RESUMO

BACKGROUND. A considerable fraction of pheochromocytomas initially suspected to be sporadic, whether or not symptomatic, are a result of germline mutations. OBJECTIVE. The purpose of this article is to compare imaging features between hereditary and sporadic pheochromocytomas. METHODS. This retrospective study included 71 patients (39 women, 32 men; median age, 48 years) who underwent adrenal pheochromocytoma resection from January 2002 to October 2021 after preoperative CT or MRI. Two radiologists independently reviewed examinations to assess features of the largest resected pheochromocytoma. Interreader agreement was assessed by prevalence-adjusted bias-adjusted kappa coefficients; a third radiologist resolved discrepancies for further analysis. Genetic testing was used to classify pheochromocytomas as hereditary or sporadic and to classify hereditary pheochromocytomas by germline mutation clusters. Symptoms associated with pheochromocytomas and preoperative biochemical laboratory values were recorded. Groups were compared using Kruskal-Wallis, Fisher exact, and chi-square tests, and false-discovery rate-adjusted p values were computed to account for multiple comparisons. RESULTS. Hereditary pheochromocytoma (n = 32), compared with sporadic pheochromocytoma (n = 39), was associated with younger median age (38 vs 52 years, p = .001) and smaller median size (24 vs 40 mm, p < .001). Interreader agreement for CT and MRI features, expressed as kappa, ranged from 0.44 to 1.00. Hereditary and sporadic pheochromocytoma showed no difference in frequency of calcifications, hemorrhage, cystic change/necrosis, or macroscopic fat on CT, or in frequency of hemorrhage, cystic change/necrosis, macroscopic fat, or microscopic fat on MRI (p > .05). When combining CT and MRI, cystic change/necrosis was observed in 35% of hereditary versus 67% of sporadic pheochromocytomas (p = .10). Hereditary pheochromocytoma, compared with sporadic, had lower frequency of symptoms (31% vs 74%; p = .004) and lower 24-hour urinary normetanephrines (1.1 vs 5.1 times upper limits of normal, p = .006). Among hereditary pheochromocytomas, cystic change/necrosis (when assessable on imaging) was present in 18% and 45% of those with cluster 1 (n = 11) and cluster 2 (n = 21) germ-line mutations, respectively. CONCLUSION. Hereditary pheochromocytomas, compared with sporadic, are detected at a younger age and smaller size, produce lower 24-hour urinary normetanephrines, are less often symptomatic, and may less frequently show cystic change/necrosis. CLINICAL IMPACT. Imaging findings may complement clinical and biochemical features in raising suspicion for a previously unsuspected germline mutation in patients with pheochromocytoma.


Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/genética , Diagnóstico por Imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Necrose , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/genética , Estudos Retrospectivos
14.
J Am Coll Radiol ; 19(3): 407-414, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34896068

RESUMO

OBJECTIVE: To evaluate the impact of structured recommendations on follow-up completion for incidental lung nodules (ILNs). METHODS: Patients with ILNs before and after implementation of structured Fleischner recommendations and electronic tracking were sampled randomly. The cohorts were compared for imaging follow-up. Multivariable logistic regression was used to assess appropriate follow-up and loss to follow-up, with independent variables including use of structured recommendations or tracking, age, sex, race, ethnicity, setting of the index test (inpatient, outpatient, emergency department), smoking history, and nodule features. RESULTS: In all, 1,301 patients met final inclusion criteria, including 255 patients before and 1,046 patients after structured recommendations or tracking. Baseline differences were found in the pre- and postintervention groups, with smaller ILNs and younger age after implementing structured recommendations. Comparing pre- versus postintervention outcomes, 40.0% (100 of 250) versus 29.5% (309 of 1,046) of patients had no follow-up despite Fleischner indications for imaging (P = .002), and among the remaining patients, 56.6% (82 of 145) versus 75.0% (553 of 737) followed up on time (P < .001). Delayed follow-up was more frequent before intervention. Differences postintervention were mostly accounted for by nodules ≤8 mm in the outpatient setting (P < .001). In multivariable analysis, younger age, White race, outpatient setting, and larger nodule size showed significant association with appropriate follow-up completion (P < .015), but structured recommendations did not. Similar results applied for loss to follow-up. DISCUSSION: Consistent use of structured reporting is likely key to mitigate selection bias when benchmarking rates of appropriate follow-up of ILN. Emergency department patients and inpatients are at high risk of missed or delayed follow-up despite structured recommendations.


Assuntos
Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Eletrônica , Humanos , Achados Incidentais , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico por imagem
15.
Abdom Radiol (NY) ; 45(11): 3800-3808, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32444889

RESUMO

PURPOSE: To identify the frequency, source, and management impact of discrepancies between the initial radiology report and expert reinterpretation occurring in the context of a hepatobiliary multidisciplinary tumor board (MTB). METHODS: This retrospective study included 974 consecutive patients discussed at a weekly MTB at a large tertiary care academic medical center over a 2-year period. A single radiologist with dedicated hepatobiliary imaging expertise attended all conferences to review and discuss the relevant liver imaging and rated the concordance between original and re-reads based on RADPEER scoring criteria. Impact on management was based on the conference discussion and reflected changes in follow-up imaging, recommendations for biopsy/surgery, or liver transplant eligibility. RESULTS: Image reinterpretation was discordant with the initial report in 19.9% (194/974) of cases (59.8%, 34.5%, 5.7% RADPEER 2/3/4 discrepancies, respectively). A change in LI-RADS category occurred in 59.8% of discrepancies. Most common causes of discordance included re-classification of a lesion as benign rather than malignant (16.0%) and missed tumor recurrence (13.9%). Impact on management occurred in 99.0% of discordant cases and included loco-regional therapy instead of follow-up imaging (19.1%), follow-up imaging instead of treatment (17.5%), and avoidance of biopsy (12.4%). 11.3% received OPTN exception scores due to the revised interpretation, and 8.8% were excluded from listing for orthotopic liver transplant. CONCLUSION: Even in a sub-specialized abdominal imaging academic practice, expert radiologist review in the MTB setting identified discordant interpretations and impacted management in a substantial fraction of patients, potentially impacting transplant allocation. The findings may impact how abdominal imaging sections best staff advanced MTBs.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia , Radiologistas , Estudos Retrospectivos
16.
AJR Am J Roentgenol ; 214(5): 1152-1157, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32097031

RESUMO

OBJECTIVE. The objective of this article is to assess radiologist concordance in characterizing thyroid nodules using the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS), focusing on the effect of radiologist experience on reader concordance. MATERIALS AND METHODS. Three experienced and three less experienced radiologists assessed 150 thyroid nodules using the TI-RADS lexicon. Percent concordance was determined for various endpoints. RESULTS. Interreader concordance for the five TI-RADS categories was 87.2% for shape, 81.2% for composition, 76.1% for echogenicity, 72.9% for margins, and 69.8% for echogenic foci. Concordance for individual features was 96.3% for rim calcifications, 90.8% for macrocalcifications, 90.1% for spongiform, 83.5% for comet tail artifact, and 77.7% for punctate echogenic foci. Concordance for the TI-RADS level and recommendation for fine-needle aspiration (FNA) were 50.4% and 78.9%, respectively. Concordance was significantly (p < 0.05) higher for less experienced readers in identifying margins (84.3% vs 67.4%), echogenic foci (76.9% vs 69.3%), comet tail artifact (89.6% vs 79.2%), and punctate echogenic foci (85.3% vs 75.5%), and lower for peripheral rim calcifications (95.0% vs 97.8 %), but was not different (p > 0.05) for the remaining categories and features. CONCLUSION. A range of TI-RADS categories, features, and recommendations for FNA had generally moderate interreader agreement among six radiologists. Our results show that concordance for numerous characteristics was significantly higher for the less experienced versus the more experienced readers. These results suggest that less experienced readers relied more on the explicit TI-RADS criteria, whereas the experienced radiologists partially relied on their accumulated experience when forming impressions. However, the overall TI-RADS level and recommendation for FNA were unaffected, supporting the robustness of the TI-RADS lexicon and its continued use in practice.


Assuntos
Competência Clínica , Radiologistas/normas , Sistemas de Informação em Radiologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Artefatos , Biópsia por Agulha Fina , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Nódulo da Glândula Tireoide/patologia
17.
Transfus Med Rev ; 34(1): 10-22, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31806414

RESUMO

Blood donors attending a donation session may be deferred from donating blood due to a failure to meet low hemoglobin (Hb) thresholds. This costs the blood donor service and donors valuable time and resources. In addition, donors who are deferred may have more symptoms, and as a direct and/or indirect effect of their experience, return rates of donors deferred for low Hb are reduced, even in repeat donors. It is therefore vital that low Hb deferral (LHD) is minimized. The aim of this updated systematic review is to expand the evidence base for factors which affect a donor's risk of deferral due to low Hb. Studies were identified by searching MEDLINE, Embase, The Cochrane Library, and the WHO International Clinical Trials Registry to March 2019. Demographic data, donor history, hematological/biological factors, and the primary outcome of deferral due to low Hb were extracted. Our primary outcome was deferral due to low Hb. Analyses were descriptive and quantitative; pooled odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by meta-analysis using random-effects models. A total of 116 studies met the inclusion criteria. Meta-analysis showed a significantly greater risk of LHD in females compared with males in studies applying universal Hb thresholds for males and females (OR 14.62 95% CI 12.43-17.19) and in those which used sex-specific thresholds (OR 5.73, 95% CI 4.36-7.53). Higher rates of LHD were also associated with increasing age in men, low body weight, shorter interdonation interval, donors of Hispanic or African descent, higher ambient temperature, donors with low ferritin levels, and donation in a fixed donor center. There was conflicting evidence on the effect of new and repeat donor status, and blood group. This work has strengthened the evidence of the previous review in identifying factors that should be considered in studies of donor deferral and highlighting areas in need of further study, including ABO and Rh blood groups, previous platelet donation, diet, smoking, time of day, and genetic data. These factors may lead to individually tailored donation criteria for safe and efficient donation in the future.


Assuntos
Seleção do Doador , Doenças Hematológicas/sangue , Hemoglobinas/metabolismo , Adulto , Doadores de Sangue/estatística & dados numéricos , Doadores de Sangue/provisão & distribuição , Seleção do Doador/métodos , Seleção do Doador/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Feminino , Doenças Hematológicas/epidemiologia , Doenças Hematológicas/etnologia , Hemoglobinas/análise , Humanos , Masculino , Fatores Sexuais , Fatores de Tempo
19.
Anticancer Res ; 31(2): 421-6, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21378320

RESUMO

A report that effects of butyrate on some cells may be mediated by activation of AMP-activated protein kinase (AMPK) prompted this study which examines if other AMPK activators can induce differentiation and inhibit proliferation of colon cancer cells in a manner similar to butyrate. Using induction of alkaline phosphatase as a marker, it was observed that compound C, an AMPK inhibitor, is able to reduce the differentiating effect of butyrate on SW1116 and Caco-2 colon cancer cells. Metformin was observed to be less effective than butyrate in the induction of alkaline phosphatase but was more effective as a growth inhibitor. Phenformin was found to be a more potent growth inhibitor than metformin and both compounds cause acidification of the medium when incubated with colon cancer cells. Combined incubation of 2-deoxyglucose with either of the biguanides prevented the acidification of the medium but enhanced the growth inhibitory effects.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias do Colo/tratamento farmacológico , Desoxiglucose/farmacologia , Fenformin/farmacologia , Adenilato Quinase/metabolismo , Fosfatase Alcalina/biossíntese , Fosfatase Alcalina/metabolismo , Butiratos/farmacologia , Células CACO-2 , Processos de Crescimento Celular/efeitos dos fármacos , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Desoxiglucose/administração & dosagem , Sinergismo Farmacológico , Ativação Enzimática/efeitos dos fármacos , Indução Enzimática/efeitos dos fármacos , Células HT29 , Humanos , Concentração de Íons de Hidrogênio , Fenformin/administração & dosagem
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