Prurigo Nodularis Mechanisms and Current Management Options.

Prurigo nodularis (PN) manifests with highly pruritic lesions that negatively impact patient quality of life. Due to the variability in manifestation, hypertrophic lichen planus, pemphigoid nodularis, and neurotic excoriations tend to mimic PN. The pathophysiology of PN is believed to be due to interactions in the neural and immune pathways causing the release of proinflammatory and pruritogenic cytokines. Dermatologic and systemic conditions, including atopic dermatitis and chronic kidney disease, accompany PN diagnoses. Patients with moderate to severe or recalcitrant PN may benefit from dupilumab, the first medication approved by the US Food and Drug Administration (FDA) to treat PN. Here, we provide an updated review of PN with a focus on its pathophysiology, histologic findings, and current treatment options.

Dynamic balance and gait impairments in Parkinson's disease: novel cholinergic patterns.

The cholinergic system has been implicated in postural deficits, in particular falls, in Parkinson's disease (PD). Falls and freezing of gait typically occur during dynamic and challenging balance and gait conditions, such as when initiating gait, experiencing postural perturbations, or making turns. However, the precise cholinergic neural substrate underlying dynamic postural and gait changes remains poorly understood. The aim of this study was to investigate whether brain vesicular acetylcholine transporter binding, as measured with [18F]-fluoroethoxybenzovesamicol binding PET, correlates with dynamic gait and balance impairments in 125 patients with PD (mean age 66.89 ± 7.71 years) using the abbreviated balance evaluation systems test total and its four functional domain sub-scores (anticipatory postural control, reactive postural control, dynamic gait, and sensory integration). Whole brain false discovery-corrected (P < 0.05) correlations for total abbreviated balance evaluation systems test scores included the following bilateral or asymmetric hemispheric regions: gyrus rectus, orbitofrontal cortex, anterior part of the dorsomedial prefrontal cortex, dorsolateral prefrontal cortex, cingulum, frontotemporal opercula, insula, fimbria, right temporal pole, mesiotemporal, parietal and visual cortices, caudate nucleus, lateral and medial geniculate bodies, thalamus, lingual gyrus, cerebellar hemisphere lobule VI, left cerebellar crus I, superior cerebellar peduncles, flocculus, and nodulus. No significant correlations were found for the putamen or anteroventral putamen. The four domain-specific sub-scores demonstrated overlapping cholinergic topography in the metathalamus, fimbria, thalamus proper, and prefrontal cortices but also showed distinct topographic variations. For example, reactive postural control functions involved the right flocculus but not the upper brainstem regions. The anterior cingulum associated with reactive postural control whereas the posterior cingulum correlated with anticipatory control. The spatial extent of associated cholinergic system changes were least for dynamic gait and sensory orientation functional domains compared to the anticipatory and reactive postural control functions. We conclude that specific aspects of dynamic balance and gait deficits in PD associate with overlapping but also distinct patterns of cerebral cholinergic system changes in numerous brain regions. Our study also presents novel evidence of cholinergic topography involved in dynamic balance and gait in PD that have not been typically associated with mobility disturbances, such as the right anterior temporal pole, right anterior part of the dorsomedial prefrontal cortex, gyrus rectus, fimbria, lingual gyrus, flocculus, nodulus, and right cerebellar hemisphere lobules VI and left crus I.

Effects of Weight Loss and Weight Maintenance on Lipoprotein Insulin Resistance Scores in Adults with Overweight and Obesity.

Background: An elevated lipoprotein insulin resistance (LP-IR) score corresponds to insulin resistance in adults with overweight and obesity, yet data are lacking regarding the impact of exercise interventions on LP-IR. The purpose of this secondary analysis was to evaluate the effects of a weight loss and weight maintenance intervention on LP-IR score in adults with overweight and obesity. Methods: Thirty sedentary adults with overweight and obesity completed a 10-week OPTIFAST® weight loss program with supervised aerobic exercise to achieve clinical weight loss (CWL) (≥7% from baseline). Aerobic exercise volume increased weekly until 700 MET min/week was reached. Participants who reached CWL were randomized to groups at volumes at either physical activity (PA-REC) or weight maintenance (WM-REC) recommendations (weeks 11-28). Plasma blood samples were analyzed via nuclear magnetic resonance spectroscopy at baseline, after weight loss (week 10), and following weight maintenance (week 28). Results: Following the weight loss phase, on average, participants significantly (p < 0.001) reduced LP-IR score (-12.1 ± 13.5), body weight (-8.9 ± 2.7%), and waist circumference (-7.7 ± 4.1 cm). During the weight maintenance phase, there were no changes in LP-IR score between exercise groups (PA-REC: 4.1 ± 13.6; WM-REC: -2.0 ± 11.2; P = 0.7). The PA-REC group had improvements in LP-IR score from baseline (49.8 ± 24.6 to 36.6 ± 27.6, P < 0.001), yet there were no within-group changes during the weight maintenance phase (P > 0.05). Conclusion: LP-IR score improved during weight loss in adults with overweight and obesity and were sustained during the weight maintenance phase in the PA-REC group. Aerobic exercise at least at minimum guidelines following CWL can preserve LP-IR score improvements and may indicate a reduced T2DM risk in adults with overweight and obesity.

The Bergen-Yale Sexual Addiction Scale (BYSAS): Longitudinal Measurement Invariance Across a Two-Year Interval.

The Bergen-Yale Sexual Addiction Scale (BYSAS; [1]) is arguably the most popular questionnaire at present for assessing sex addiction. Employing Confirmatory Factor Analysis (CFA) and treating item scores as ordered categorical, we applied Weighted Least Square Mean and Variance Adjusted Chi-Square (WLSMV) extraction to investigate the longitudinal measurement and structural invariance of ratings on the BYSAS among 276 adults (mean = 31.86 years; SD = 9.94 years; 71% male) over a two-year period, with ratings at three yearly intervals. Overall, there was support for configural invariance, full loading, full threshold, the full unique factor invariance; and all structural (latent variances and covariances) components. Additionally, there was no difference in latent mean scores across the three-time points. The psychometric and practical implications of the findings are discussed.

A Rare Case of an Adult with Spinal Cord Injury Without Neuroimaging Abnormality (SCIWONA).

BACKGROUND: Spinal cord injury without radiographic abnormality (SCIWORA) is defined as having clinical symptoms of traumatic myelopathy with no radiographic or computed tomographic features of spinal fracture or instability. An abnormal finding, such as a fracture, subluxation, or abnormal intersegmental motion at the level of the spinal cord injury, excludes SCIWORA as the diagnosis. Prevalence of SCIWORA is highest among children younger than 8 years, and is a diagnosis seen primarily in children, owing to anatomic differences that put children at more risk of this condition. In more recent years, with the increasing use of magnetic resonance imaging in patients with suspected spinal cord injury, a new term, spinal cord injury without neuroimaging abnormality (SCIWONA) has been suggested as a more specific way to describe cases of SCIWORA that have negative neuroimaging. CASE REPORT: Here we describe a case of a woman who presented with symptoms consistent with a spinal cord injury after a traumatic fall. Her presentation and imaging were consistent with SCIWONA. The patient subsequently had rapid and complete recovery of her neurologic function. Why Should an Emergency Physician Be Aware of This? Early recognition of SCIWONA and subsequent medical management is imperative for improved outcomes for these patients. Operative treatment is rare and typically only necessary in patients with consistent spinal cord instability.

Trauma-informed precepting: A novel curriculum for faculty development.

PURPOSE: Traumatic experiences are ubiquitous and associated with negative impacts on health and wellbeing in patients, students, and clinicians. Trauma-informed care (TIC) is a harm reduction framework that aims to minimize re-traumatization and the negative health impacts of trauma. TIC is increasingly being incorporated into undergraduate medical education (UME) curricula; however, to date, there is no standardized curriculum to support faculty in precepting TIC clinical skills. METHODS: We created a series of five educational modules in an asynchronous online format to support faculty in the instruction and precepting of TIC clinical skills in UME. The modules instruct on trauma epidemiology, trauma-informed clinical skills, trauma-informed precepting, and trauma-informed self-care (TISC). The modules are interactive and utilize multimedia content. RESULTS: Fifty-three faculty members of the primary care clerkship participated in the modules. After the modules, faculty demonstrated increased knowledge of TIC, though their comfort in applying principles with patients and students was unchanged. DISCUSSION: We present a novel, standardized curriculum to support faculty in the practice and precepting of TIC clinical skills. The intervention is shown to promote knowledge surrounding TIC. In the future, pairing these asynchronous modules with in-person training may be necessary to improve comfort with the application of these skills.

Cognitive and Cholinergic Systems Trajectories in Parkinson Disease.

Objective: Cognitive decline in Parkinson disease (PD) is a disabling and highly variable non-motor feature. While cholinergic systems degeneration is linked to cognitive impairments in PD, most prior research reported cross-sectional associations. We aimed to fill this gap by investigating whether baseline regional cerebral vesicular acetylcholine transporter ligand [ 18 F]-fluoroethoxybenzovesamicol ([ 18 F]-FEOBV) binding predicts longitudinal cognitive changes in mild to moderate, non-demented PD subjects. Methods: Seventy-five non-demented, mild-moderate PD subjects received baseline standardized cognitive evaluations and [ 18 F]-FEOBV PET imaging with repeat cognitive evaluations 2 years later. Participants were classified into four cognitive classes based on stability or change in cognition: Persistent normal (no MCI at baseline and follow-up), Persistent MCI, MCI conversion, and MCI reversion. Whole-brain voxel comparisons with normal controls, and voxel-based and cluster volume-of-interest correlation analyses with longitudinal cognitive changes were performed. Results: Whole-brain voxel comparisons of each class with a matched control group revealed unique bi-directional differences in baseline regional [ 18 F]-FEOBV binding. Increased regional [ 18 F]-FEOBV binding in predominantly anterior cortical and sub-cortical regions was found in the persistent normal and MCI reversion groups. Whole-brain voxel correlation analysis between baseline [ 18 F]-FEOBV binding and two-year longitudinal percent changes in cognition identified a specific regional pattern of reduced posterior cortical, limbic and paralimbic [ 18 F]-FEOBV binding predictive of global cognitive declines and across five cognitive domains at two-year follow-ups. Interpretation: Cholinergic system changes correlate with varying cognitive trajectories in mild-moderate PD. Upregulation of cholinergic neurotransmission may be an important compensatory process in mild-moderate PD.

Evaluation and Surgical Management of Multiple Endocrine Neoplasias.

Multiple endocrine neoplasia (MEN) syndromes are rare autosomal dominant diseases that are associated with a mixture of both endocrine and non-endocrine tumors. Traditionally, there are 2 types of MEN that have unique clinical associations: MEN 1 (parathyroid hyperplasia, pancreatic neuroendocrine tumors, and pituitary tumors) and MEN 2 (medullary thyroid carcinoma and pheochromocytoma), which is further classified into MEN 2A (adds parathyroid adenomas) and 2B (adds ganglioneuromas and marfanoid habitus). Many of the endocrine tumors are resected surgically, and the pre, intra, and postoperative management strategies used must take into account the high recurrence rates asscioated with MEN tumors.

Overexpression of human DNA polymerase theta is a biomarker of aggressive and DNA repair-deficient papillary thyroid cancers.

BACKGROUND: DNA polymerase theta (POLQ) is an enzyme that repairs double-strand DNA breaks. POLQ is overexpressed in several cancer types, and increased expression is associated with a poor prognosis. Ablating POLQ function in vitro increases drug sensitivity to agents that cause double-strand DNA breaks, including chemotherapies and ionizing radiation. POLQ's role in thyroid cancer remains poorly understood. METHODS: Expression of POLQ and other genes of interest were analyzed in 513 papillary thyroid cancers (505 primary tumors and 8 metastatic lesions) and 59 normal thyroid samples available in the Cancer Genome Atlas. The Cancer Genome Atlas RNA and DNA sequencing data were queried with the Xena platform. The Recombination Proficiency Score was calculated to assess DNA repair efficiency. Other signaling events associated with thyroid tumorigenesis and clinical outcomes were analyzed. Univariate and multivariate analyses were performed. Treatment with the POLQ inhibitors ART558 and Novobiocin tested the effect of POLQ inhibition on in vitro thyroid cancer growth. RESULTS: POLQ expression was increased in papillary thyroid cancers compared to normal thyroid tissue (P < .05). POLQ expression levels were inversely correlated with Recombination Proficiency Score levels (P < .05). POLQ expression was highest in tall cell papillary thyroid cancers and in metastases. Higher POLQ expression was also associated with dedifferentiation, BRAF signaling, and shorter progression-free intervals (P < .05). Treatment with POLQ inhibitors decreased in vitro thyroid cancer growth (P < .05). CONCLUSION: These findings suggest that increased POLQ expression could serve as a valuable clinical marker and a potential therapeutic target in the treatment of thyroid cancer.

Sensitivity to and Control of Distraction: Distractor-Entrained Oscillation and Frontoparietal EEG Gamma Synchronization.

While recent advancements have been made towards a better understanding of the involvement of the prefrontal cortex (PFC) in the context of cognitive control, the exact mechanism is still not fully understood. Successful behavior requires the correct detection of goal-relevant cues and resisting irrelevant distractions. Frontal parietal networks have been implicated as important for maintaining cognitive control in the face of distraction. The present study investigated the role of gamma-band power in distraction resistance and frontoparietal networks, as its increase is linked to cholinergic activity. We examined changes in gamma activity and their relationship to frontoparietal top-down modulation for distractor challenges and to bottom-up distractor processing. Healthy young adults were tested using a modified version of the distractor condition sustained attention task (dSAT) while wearing an EEG. The modified distractor was designed so that oscillatory activities could be entrained to it, and the strength of entrainment was used to assess the degree of distraction. Increased top-down control during the distractor challenge increased gamma power in the left parietal regions rather than the right prefrontal regions predicted from rodent studies. Specifically, left parietal gamma power increased in response to distraction where the amount of this increase was negatively correlated with the neural activity reflecting bottom-up distractor processing in the visual area. Variability in gamma power in right prefrontal regions was associated with increased response time variability during distraction. This may suggest that the right prefrontal region may contribute to the signaling needed for top-down control rather than its implementation.

The effects of Facebook and Instagram on the 2020 election: A deactivation experiment.

We study the effect of Facebook and Instagram access on political beliefs, attitudes, and behavior by randomizing a subset of 19,857 Facebook users and 15,585 Instagram users to deactivate their accounts for 6 wk before the 2020 U.S. election. We report four key findings. First, both Facebook and Instagram deactivation reduced an index of political participation (driven mainly by reduced participation online). Second, Facebook deactivation had no significant effect on an index of knowledge, but secondary analyses suggest that it reduced knowledge of general news while possibly also decreasing belief in misinformation circulating online. Third, Facebook deactivation may have reduced self-reported net votes for Trump, though this effect does not meet our preregistered significance threshold. Finally, the effects of both Facebook and Instagram deactivation on affective and issue polarization, perceived legitimacy of the election, candidate favorability, and voter turnout were all precisely estimated and close to zero.

Surgical journal clubs: Navigating the post-pandemic landscape.

Pandemic-related distancing regulations gave medical educators at our college an opportunity to reimagine and expand our evidenced-based medicine curriculum to an asynchronous, virtual format. We share the experience of course directors, faculty, and students with our new surgical journal club format. Our goal was to support learners' critical appraisal skills of the surgical literature through active learning modalities such as visual abstract generation and audio-synopsis creation. We included surgeons whose practice locations and schedules may preclude participation. The curriculum was applied to our pre-existing community-based journal clubs. The asynchronous, virtual format allowed us to expand these journal clubs to include rural surgeons.

Cost-Effectiveness of Parathyroid Cryopreservation and Autotransplantation.

Importance: Delayed autotransplantation of cryopreserved parathyroid tissue (DACP) is the only surgical treatment for permanent postoperative hypoparathyroidism. Studies suggest that only a small minority of cryopreserved samples are ultimately autotransplanted with highly variable outcomes. For these reasons, many have questioned the economic utility of the process, although, to the authors' knowledge, this has never been formally studied. Objective: To report the clinical outcomes of parathyroid cryopreservation and DACP at a large academic institution and to determine the cost-effectiveness of this treatment. Design, Setting, and Participants: An institutional review board-approved, retrospective review of patients at a single institution who underwent DACP over a 17-year period was conducted with a median follow-up of 48.2 months. A forward-looking cost-utility analysis was then performed to determine the economic utility of cryopreservation/DACP vs usual care (monitoring and supplementation). Patients who had parathyroid tissue in cryopreserved storage between August 2005 to September 2022 at a single-center, academic, quaternary care center were identified. Exposure: Parathyroid cryopreservation and DACP. Main Outcomes and Measures: Graft functionality, clinical outcomes, and cost utility using a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY). Results: A total of 591 patients underwent cryopreservation. Of these, 10 patients (1.7%; mean [SD] age, 45.6 [17.9] years; 6 male [60%]) underwent DACP. A minority of autografts (2 [20%]) were subsequently fully functional, one-half (5 [50%]) were partially functional, and 3 (30%) were not functional. The cost-utility model estimated that at a large academic center over 10 years, the additional cost of 591 patients undergoing cryopreservation and 10 patients undergoing autotransplantation would be $618 791.64 (2022 dollars) and would add 8.75 QALYs, resulting in a cost per marginal QALY of $70 719.04, which is less than the common willingness-to-pay threshold of $100 000/QALY. Conclusions and Relevance: The reimplantation rate of cryopreserved tissue was low (<2%), but when implanted, autografts were at least partially functional 70% of the time. In the first-ever, to the authors' knowledge, formal cost analysis for this treatment, results of the current model suggest that cryopreservation and autotransplantation were cost-effective compared with the usual care for hypoparathyroidism at a large, academic institution. It is recommended that each surgical center consider whether the economic and logistical commitments necessary for cryopreservation are worthwhile for their individual needs.

Translating the user-avatar bond into depression risk: A preliminary machine learning study.

Research has shown a link between depression risk and how gamers form relationships with their in-game figure of representation, called avatar. This is reinforced by literature supporting that a gamer's connection to their avatar may provide broader insight into their mental health. Therefore, it has been argued that if properly examined, the bond between a person and their avatar may reveal information about their current or potential struggles with depression offline. To examine whether the connection with an individuals' avatars may reveal their risk for depression, longitudinal data from 565 adults/adolescents (Mage = 29.3 years, SD = 10.6) were evaluated twice (six months apart). Participants completed the User-Avatar-Bond [UAB] scale and Depression Anxiety Stress Scale to measure avatar bond and depression risk. A series of tuned and untuned artificial intelligence [AI] classifiers analyzed their responses concurrently and prospectively. This allowed the examination of whether user-avatar bond can provide cross-sectional and predictive information about depression risk. Findings revealed that AI models can learn to accurately and automatically identify depression risk cases, based on gamers' reported UAB, age, and length of gaming involvement, both at present and six months later. In particular, random forests outperformed all other AIs, while avatar immersion was shown to be the strongest training predictor. Study outcomes demonstrate that UAB can be translated into accurate, concurrent, and future, depression risk predictions via trained AI classifiers. Assessment, prevention, and practice implications are discussed in the light of these results.

Rotator Cuff Repair With Patch Augmentation Is Associated With Lower Retear Rates for Large Tears: A Systematic Review of Randomized Controlled Trials.

PURPOSE: To perform a systematic review of randomized controlled trials comparing clinical outcomes of rotator cuff repair with and without patch augmentation. METHODS: A systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines by searching PubMed, the Cochrane Library, and Embase to identify randomized controlled trials that directly compared outcomes between rotator cuff repair (RCR) with versus without patch augmentation. Patients were evaluated based on retear rate, histological outcomes, radiological outcomes, and patient-reported outcomes (Constant score; American Shoulder and Elbow Surgeons [ASES] score; University of California-Los Angeles shoulder scale; Simple Shoulder Test; EuroQol-visual analog scale; Disabilities of the Arm, Shoulder and Hand score; and PENN shoulder score questionnaire). RESULTS: Six studies (1 level I, 5 level II) met inclusion criteria, including 188 patients undergoing RCR alone (Control) and 193 patients undergoing RCR with patch augmentation (Patch). Patient age ranged from 56.0 to 68.0 years. The mean follow-up time ranged from 14.0 to 68.4 months. The average body mass index ranged from 24.4 to 29.4, and the overall percentage of males ranged from 32.5% to 82.3%. Three studies found significantly decreased retear rates with patch augmentation. The retear rate ranged from 34.0% to 65.4% in the Control group and 9.1% to 52.9% in the Patch group. One study found a significant difference for the Constant score favoring the Patch group. Two studies found a significant difference for the ASES score favoring the Patch group. One study found significantly better results with patch augmentation in terms of repaired tendon thickness and footprint coverage, based on magnetic resonance imaging. CONCLUSIONS: Patch augmentation of rotator cuff repairs may be associated with lower retear rates for large tears. There is limited evidence to suggest that patch augmentation is associated with improved patient-reported outcomes. LEVEL OF EVIDENCE: Level II, systematic review of level I and II studies.

Reducing annotation burden in MR: A novel MR-contrast guided contrastive learning approach for image segmentation.

BACKGROUND: Contrastive learning, a successful form of representational learning, has shown promising results in pretraining deep learning (DL) models for downstream tasks. When working with limited annotation data, as in medical image segmentation tasks, learning domain-specific local representations can further improve the performance of DL models. PURPOSE: In this work, we extend the contrastive learning framework to utilize domain-specific contrast information from unlabeled Magnetic Resonance (MR) images to improve the performance of downstream MR image segmentation tasks in the presence of limited labeled data. METHODS: The contrast in MR images is controlled by underlying tissue properties (e.g., T1 or T2) and image acquisition parameters. We hypothesize that learning to discriminate local representations based on underlying tissue properties should improve subsequent segmentation tasks on MR images. We propose a novel constrained contrastive learning (CCL) strategy that uses tissue-specific information via a constraint map to define positive and negative local neighborhoods for contrastive learning, embedding this information in the representational space during pretraining. For a given MR contrast image, the proposed strategy uses local signal characteristics (constraint map) across a set of related multi-contrast MR images as a surrogate for underlying tissue information. We demonstrate the utility of the approach for downstream: (1) multi-organ segmentation tasks in T2-weighted images where a DL model learns T2 information with constraint maps from a set of 2D multi-echo T2-weighted images (n = 101) and (2) tumor segmentation tasks in multi-parametric images from the public brain tumor segmentation (BraTS) (n = 80) dataset where DL models learn T1 and T2 information from multi-parametric BraTS images. Performance is evaluated on downstream multi-label segmentation tasks with limited data in (1) T2-weighted images of the abdomen from an in-house Radial-T2 (Train/Test = 30/20), (2) public Cartesian-T2 (Train/Test = 6/12) dataset, and (3) multi-parametric MR images from the public brain tumor segmentation dataset (BraTS) (Train/Test = 40/50). The performance of the proposed CCL strategy is compared to state-of-the-art self-supervised contrastive learning techniques. In each task, a model is also trained using all available labeled data for supervised baseline performance. RESULTS: The proposed CCL strategy consistently yielded improved Dice scores, Precision, and Recall metrics, and reduced HD95 values across all segmentation tasks. We also observed performance comparable to the baseline with reduced annotation effort. The t-SNE visualization of features for T2-weighted images demonstrates its ability to embed T2 information in the representational space. On the BraTS dataset, we also observed that using an appropriate multi-contrast space to learn T1+T2, T1, or T2 information during pretraining further improved the performance of tumor segmentation tasks. CONCLUSIONS: Learning to embed tissue-specific information that controls MR image contrast with the proposed constrained contrastive learning improved the performance of DL models on subsequent segmentation tasks compared to conventional self-supervised contrastive learning techniques. The use of such domain-specific local representations could help understand, improve performance, and mitigate the scarcity of labeled data in MR image segmentation tasks.

Molecular characteristics of isthmus papillary thyroid cancers: Supporting evidence for unfavorable clinical behavior.

BACKGROUND: Previous studies demonstrate isthmus thyroid nodules are more likely to be malignant than lobar nodules. Additional data suggest that isthmus papillary thyroid cancers (PTCs) are more aggressive than lobar PTCs. We hypothesize that isthmus PTCs have a more unfavorable molecular profile. METHODS: The Cancer Genome Atlas (TCGA) database was queried to analyze clinical, mutation and gene expression data of isthmus PTCs compared to non-isthmus PTCs. RESULTS: We analyzed characteristics of 472 â€‹PTCs, including 19 isthmus PTCs. There were no significant differences between isthmus and non-isthmus PTC demographic and clinical variables or the frequency of RAS family, fusion driver, TERT, and tumor suppressor gene mutations. There was a trend towards increased BRAF mutations (68% vs 55%, p â€‹= â€‹0.28). A more aggressive gene expression profile was observed in isthmus PTC compared to lobar/multifocal PTC with differences in ERK score (19.4 vs 7.71, p â€‹< â€‹0.05) and TDS score (-0.58 vs 0.02, p â€‹< â€‹0.05). CONCLUSIONS: These results provide a possible molecular explanation for the more aggressive behavior reported in isthmus PTCs.