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Brain : a Journal of Neurology Jul 2019MRI has improved the diagnostic work-up of multiple sclerosis, but inappropriate image interpretation and application of MRI diagnostic criteria contribute to... (Review)
Review
MRI has improved the diagnostic work-up of multiple sclerosis, but inappropriate image interpretation and application of MRI diagnostic criteria contribute to misdiagnosis. Some diseases, now recognized as conditions distinct from multiple sclerosis, may satisfy the MRI criteria for multiple sclerosis (e.g. neuromyelitis optica spectrum disorders, Susac syndrome), thus making the diagnosis of multiple sclerosis more challenging, especially if biomarker testing (such as serum anti-AQP4 antibodies) is not informative. Improvements in MRI technology contribute and promise to better define the typical features of multiple sclerosis lesions (e.g. juxtacortical and periventricular location, cortical involvement). Greater understanding of some key aspects of multiple sclerosis pathobiology has allowed the identification of characteristics more specific to multiple sclerosis (e.g. central vein sign, subpial demyelination and lesional rims), which are not included in the current multiple sclerosis diagnostic criteria. In this review, we provide the clinicians and researchers with a practical guide to enhance the proper recognition of multiple sclerosis lesions, including a thorough definition and illustration of typical MRI features, as well as a discussion of red flags suggestive of alternative diagnoses. We also discuss the possible place of emerging qualitative features of lesions which may become important in the near future.
Topics: Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Neuroimaging; Practice Guidelines as Topic
PubMed: 31209474
DOI: 10.1093/brain/awz144 -
CytoJournal 2021For every 100,000 women in the United States, eight new cervical cancer cases and two deaths are reported as per the most recent (2017) Center of Disease Control and... (Review)
Review
For every 100,000 women in the United States, eight new cervical cancer cases and two deaths are reported as per the most recent (2017) Center of Disease Control and Prevention statistics. Of all the gynecologic cancers (ovary, uterus, cervix, vagina, and vulva), only cervical cancer has a screening test. Cervical Pap test (or Pap smear) is the best screening method for cervical precancerous lesions and is best reported using a unified and a well-established reporting system like The Bethesda System. In this system, "Epithelial cell abnormality: Squamous" includes squamous intraepithelial lesion (SIL) category which encompasses a spectrum of squamous cell lesions starting from the precancerous lesions of low-grade SIL (LSIL) to high-grade SIL (HSIL), and ultimately invasive squamous cell carcinoma. However, depending on the qualitative and quantitative limitations with the specimen, some equivocal morphological features suggestive of squamous cell abnormality may fall under equivocal category: "Atypical Squamous Cells" (ASCs), which are subdivided into two categories; "Atypical Squamous Cells of Undetermined Significance" (ASC-US) or "Atypical Squamous Cells, HSIL cannot be excluded" (ASC-H), based on the suspected underlying lesion LSIL versus HSIL, respectively. This review provides the key cytologic features that distinguish Bethesda squamous categories from other important entities, using algorithmic approach and illustrations of common cytomorphologic patterns for clear identification of those entities in practice. The important mimickers which may be considered during the differential interpretation of SIL are discussed and presented here in a brief cytomorphologic review.
PubMed: 34345247
DOI: 10.25259/Cytojournal_24_2021 -
Multiple Sclerosis (Houndmills,... May 2023Paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs) have been posited as markers of chronic active lesions (CALs).
BACKGROUND
Paramagnetic rim lesions (PRLs) and slowly expanding lesions (SELs) have been posited as markers of chronic active lesions (CALs).
OBJECTIVE
To assess the lesion-level concordance of PRLs and SELs in MS and to characterize changes in brain tissue integrity in CALs over time.
METHODS
MRIs were analyzed from a substudy of AFFINITY [NCT03222973], a phase 2 trial of opicinumab in relapsing MS. Assessments included (1) identification of SELs based on longitudinal MRIs over 72 weeks, and identification of PRLs on susceptibility-weighted imaging (SWI) filtered phase images at week 72; (2) evaluation of subject-level correlation of SEL and PRL counts, volumes, and degree of lesion-level overlap between SELs and PRLs; and (3) characterization of tissue integrity over time in overlapping and non-overlapping SELs and PRLs.
RESULTS
In 41 subjects, 119 chronic PRLs and 267 SELs were detected. Of 119 (39.5%) chronic PRLs, 47 co-localized with a SEL; 46/267 (17.2%) SELs co-localized with a PRL. PRLs co-localized with SELs showed expansion and worsening microstructural damage over time. SELs with and without co-localization with PRLs showed ongoing tissue damage.
CONCLUSIONS
Chronic MS lesions identified as both PRL and SEL were associated with the most severe accumulation of tissue damage.
TRIAL REGISTRATION
AFFINITY [NCT03222973].
Topics: Humans; Multiple Sclerosis; Brain; Magnetic Resonance Imaging; Longitudinal Studies
PubMed: 37036134
DOI: 10.1177/13524585231162262 -
Orthopaedic Surgery Oct 2023Morel-Lavallée lesion is a closed soft tissue degloving injury usually associated with high-velocity trauma. It most commonly occurs in the thigh, hip, and pelvis.... (Review)
Review
Morel-Lavallée lesion is a closed soft tissue degloving injury usually associated with high-velocity trauma. It most commonly occurs in the thigh, hip, and pelvis. Because such lesions are prone to a missed or delayed diagnosis, it may present a potential risk of infection at the fracture site once it progresses. Therefore, timely identification and management of Morel-Lavallée lesion is crucial. Moreover, there are no relevant guidelines for the treatment of Morel-Lavallée lesion. Based on the above facts, we reviewed the etiology, epidemiology, pathophysiology, clinical presentation, imaging features, treatment, prognosis, and complications of Morel-Lavallée lesion with the aim of providing a comprehensive overview of Morel-Lavallée lesion, increasing awareness of this injury among orthopaedic surgeons, and thus providing a management algorithm that can be applied to this injury.
PubMed: 37526135
DOI: 10.1111/os.13826 -
Journal of Clinical Oncology : Official... Jun 2022Metastatic breast cancer (mBrCa) is most often an incurable disease with only modest responses to available immunotherapies. This study investigates the immunogenicity...
PURPOSE
Metastatic breast cancer (mBrCa) is most often an incurable disease with only modest responses to available immunotherapies. This study investigates the immunogenicity of somatic mutations in breast cancer and explores the therapeutic efficacy in a pilot trial of mutation-reactive tumor-infiltrating lymphocytes (TILs) in patients with metastatic disease.
PATIENTS AND METHODS
Forty-two patients with mBrCa refractory to previous lines of treatment underwent surgical resection of a metastatic lesion(s), isolation of TIL cultures, identification of exomic nonsynonymous tumor mutations, and immunologic screening for neoantigen reactivity. Clinically eligible patients with appropriate reactivity were enrolled into one cohort of an ongoing phase II pilot trial of adoptive cell transfer of selected neoantigen-reactive TIL, with a short course of pembrolizumab (ClinicalTrials.gov identifier: NCT01174121).
RESULTS
TILs were isolated and grown in culture from the resected lesions of all 42 patients with mBrCa, and a median number of 112 (range: 6-563) nonsynonymous mutations per patient were identified. Twenty-eight of 42 (67%) patients contained TIL that recognized at least one immunogenic somatic mutation (median: 3 neoantigens per patient, range: 1-11), and 13 patients demonstrated robust reactivity appropriate for adoptive transfer. Eight patients remained clinically eligible for treatment, and six patients were enrolled on a protocol of adoptive cell transfer of enriched neoantigen-specific TIL, in combination with pembrolizumab (≤ 4 doses). Objective tumor regression was noted in three patients, including one complete response (now ongoing over 5.5 years) and two partial responses (6 and 10 months).
CONCLUSION
Most patients with breast cancer generated a natural immune response targeting the expressed products of their cancer mutations. Adoptive transfer of TIL is a highly personalized experimental option for patients with mBrCa shown to be capable of mediating objective responses in this pilot trial and deserves further study.
Topics: Breast Neoplasms; Female; Humans; Immunotherapy, Adoptive; Lymphocytes, Tumor-Infiltrating; Mutation; Transplantation, Autologous
PubMed: 35104158
DOI: 10.1200/JCO.21.02170 -
Archives of Pathology & Laboratory... Aug 2010Basaloid follicular hamartoma is a benign lesion of important consideration because it can be mistaken both clinically and histologically for basal cell carcinoma. The... (Review)
Review
Basaloid follicular hamartoma is a benign lesion of important consideration because it can be mistaken both clinically and histologically for basal cell carcinoma. The formation of basaloid follicular hamartoma has been linked to a mutation in the patched gene, which is part of the same pathway implicated in nevoid basal cell carcinoma syndrome. While these hamartomas are considered benign lesions, malignant growths have been reported to arise within them, which raises the question, "Is basaloid follicular hamartoma a premalignant lesion?" Correct identification allows for periodic monitoring for malignant transformation, while sparing patients unnecessary surgery. Treatment strategies, including experimental therapies, are reviewed.
Topics: Carcinoma, Basal Cell; Diagnosis, Differential; Hair Diseases; Hair Follicle; Hamartoma; Humans; Mutation; Patched Receptors; Receptors, Cell Surface; Skin Neoplasms
PubMed: 20670146
DOI: 10.5858/2008-0620-RS.1 -
Biomedical Journal Aug 2022Classification of glomerular diseases and identification of glomerular lesions require careful morphological examination by experienced nephropathologists, which is...
BACKGROUND
Classification of glomerular diseases and identification of glomerular lesions require careful morphological examination by experienced nephropathologists, which is labor-intensive, time-consuming, and prone to interobserver variability. In this regard, recent advance in machine learning-based image analysis is promising.
METHODS
We combined Mask Region-based Convolutional Neural Networks (Mask R-CNN) with an additional classification step to build a glomerulus detection model using human kidney biopsy samples. A Long Short-Term Memory (LSTM) recurrent neural network was applied for glomerular disease classification, and another two-stage model using ResNeXt-101 was constructed for glomerular lesion identification in cases of lupus nephritis.
RESULTS
The detection model showed state-of-the-art performance on variedly stained slides with F1 scores up to 0.944. The disease classification model showed good accuracies up to 0.940 on recognizing different glomerular diseases based on H&E whole slide images. The lesion identification model demonstrated high discriminating power with area under the receiver operating characteristic curve up to 0.947 for various glomerular lesions. Models showed good generalization on external testing datasets.
CONCLUSION
This study is the first-of-its-kind showing how each step of kidney biopsy interpretation carried out by nephropathologists can be captured and simulated by machine learning models. The models were integrated into a whole slide image viewing and annotating platform to enable nephropathologists to review, correct, and confirm the inference results. Further improvement on model performances and incorporating inputs from immunofluorescence, electron microscopy, and clinical data might realize actual clinical use.
Topics: Deep Learning; Humans; Image Processing, Computer-Assisted; Machine Learning; Neural Networks, Computer; ROC Curve
PubMed: 34506971
DOI: 10.1016/j.bj.2021.08.011 -
Scientific Reports Sep 2022We consider machine-learning-based lesion identification and malignancy prediction from clinical dermatological images, which can be indistinctly acquired via smartphone...
We consider machine-learning-based lesion identification and malignancy prediction from clinical dermatological images, which can be indistinctly acquired via smartphone or dermoscopy capture. Additionally, we do not assume that images contain single lesions, thus the framework supports both focal or wide-field images. Specifically, we propose a two-stage approach in which we first identify all lesions present in the image regardless of sub-type or likelihood of malignancy, then it estimates their likelihood of malignancy, and through aggregation, it also generates an image-level likelihood of malignancy that can be used for high-level screening processes. Further, we consider augmenting the proposed approach with clinical covariates (from electronic health records) and publicly available data (the ISIC dataset). Comprehensive experiments validated on an independent test dataset demonstrate that (1) the proposed approach outperforms alternative model architectures; (2) the model based on images outperforms a pure clinical model by a large margin, and the combination of images and clinical data does not significantly improves over the image-only model; and (3) the proposed framework offers comparable performance in terms of malignancy classification relative to three board certified dermatologists with different levels of experience.
Topics: Algorithms; Dermoscopy; Humans; Machine Learning; Melanoma; Skin Neoplasms
PubMed: 36151257
DOI: 10.1038/s41598-022-20168-w -
Frontiers in Neurology 2017Post-stroke depression (PSD) affects approximately one-third of all stroke patients. It hinders rehabilitation and is associated with worse functional outcome and... (Review)
Review
Post-stroke depression (PSD) affects approximately one-third of all stroke patients. It hinders rehabilitation and is associated with worse functional outcome and increased mortality. Since the identification of PSD is a significant clinical problem, clinicians and researchers have tried to identify predictors that indicate patients at risk of developing PSD. This also includes the research question whether there is an association between PSD and stroke lesion characteristics, e.g., lesion size and lesion location. Early studies addressing this question are largely limited by technical constraints and, thus, focused on simple lesion characteristics such as lesion side or proximity of the lesion to the frontal pole of the brain. More recent studies have addressed the impact of involvement of specific neuronal circuits in the stroke lesion. State-of-the-art methods of lesion symptom mapping to study PSD have only been applied to small patient samples. Overall, results are controversial and no clear pattern of stroke lesions associated with PSD has emerged, though there are findings suggesting that more frontal stroke lesions are associated with higher incidence of PSD. Available studies are hampered by methodological limitations, including drawbacks of lesion analysis methods, small sample size, and the issue of patient selection. These limitations together with differences in approaches to assess PSD and in methods of image analysis limit the comparability of results from different studies. To summarize, as of today no definite association between lesion location and PSD can be ascertained and the understanding of PSD rests incomplete. Further insights are expected from the use of modern lesion inference analysis methods in larger patient samples taking into account standardized assessment of possible confounding parameters, such as stroke treatment and reperfusion status.
PubMed: 28983281
DOI: 10.3389/fneur.2017.00498