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result(s) for
"Hinkle, David"
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Automated detection of giant cell arteritis from temporal artery biopsy specimens using deep learning approaches
2026
This pilot study aims to develop a deep learning model for classifying temporal artery biopsy (TAB) histological sections to detect histologic patterns indicative of giant cell arteritis (GCA). Formalin-fixed, paraffin-embedded, hematoxylin and eosin (H&E) -stained, tissue specimens from 472 patients who underwent TAB between January 1, 2000, and December 31, 2019, were digitized at 20x magnification. Individual artery regions were identified, extracted, and resized into individual image patches/tiles, referred to as regions of interest (ROIs), for GCA detection. A ResNet model was trained using these ROIs after data augmentation techniques. Performance metrics such as accuracy and area under the receiver operating characteristic curve (AUC) were used to evaluate the model. The training set included 336 slides (100 positive, 236 negative), and the test set comprised 136 slides (40 positive, 96 negative). The ResNet model achieved an accuracy of 96.32% with an AUC of 0.99 on the validation set, and 92.32% accuracy with an AUC of 0.93 on a held-out test set. Model predictions were validated using GradCAM visualizations which qualitatively confirmed the model’s performance. This study demonstrates the effectiveness of deep neural network methods in automating the detection of GCA from TAB, and this approach holds promise for speeding up diagnosis and improving test sensitivity.
Journal Article
Wearable Surface Electromyography System to Predict Freeze of Gait in Parkinson’s Disease Patients
2024
Freezing of gait (FOG) is a disabling yet poorly understood paroxysmal gait disorder affecting the vast majority of patients with Parkinson’s disease (PD) as they reach advanced stages of the disorder. Falling is one of the most disabling consequences of a FOG episode; it often results in injury and a future fear of falling, leading to diminished social engagement, a reduction in general fitness, loss of independence, and degradation of overall quality of life. Currently, there is no robust or reliable treatment against FOG in PD. In the absence of reliable and effective treatment for Parkinson’s disease, alleviating the consequences of FOG represents an unmet clinical need, with the first step being reliable FOG prediction. Current methods for FOG prediction and prevention cannot provide real-time readouts and are not sensitive enough to detect changes in walking patterns or balance. To fill this gap, we developed an sEMG system consisting of a soft, wearable garment (pair of shorts and two calf sleeves) embedded with screen-printed electrodes and stretchable traces capable of picking up and recording the electromyography activities from lower limb muscles. Here, we report on the testing of these garments in healthy individuals and in patients with PD FOG. The preliminary testing produced an initial time-to-onset commencement that persisted > 3 s across all patients, resulting in a nearly 3-fold drop in sEMG activity. We believe that these initial studies serve as a solid foundation for further development of smart digital textiles with integrated bio and chemical sensors that will provide AI-enabled, medically oriented data.
Journal Article
The microbiological spectrum, antimicrobial resistance pattern, and visual outcomes of endogenous endophthalmitis in West Virginia 2009–2019
2022
PurposeTo report the microbiological spectrum, antimicrobial resistance patterns, and visual outcomes in patients with endogenous endophthalmitis (EE).MethodsThis was a retrospective study of 50 patients with culture-positive EE managed in a tertiary referral center between October 2009 and 2019. Clinical, microbiology analysis, and antimicrobial resistance were reviewed. A multivariable linear regression analysis was used for identifying risk factors associated with worse visual outcomes.ResultsFifty organisms were identified, 62% bacterial and 38% fungal. The most common bacterial organism was Staphylococcus aureus (75% methicillin resistant), and Candida was the most common fungal species. Multidrug resistance was observed in methicillin-resistant Staphylococcus aureus (MRSA) isolates against clindamycin, daptomycin, and fluoroquinolones. The distributions of the final visual acuity (VA) between the bacterial and fungal groups were significantly different, and the visual outcomes in the bacterial group tended to be worse (p = 0.01). The distributions of enucleation status were significantly higher in bacterial EE (35%) than fungal EE (5.3%) (p = 0.02). Results from the multivariable linear regression analysis revealed that older age was significantly associated with worse visual outcome (coef = 0.03; p = 0.02), while fungal infections were associated with better outcomes (coef = − 0.87; p = 0.01). Intravenous drug use (coef = 0.87; p = 0.054) was a marginally significant factor associated with worse visual outcomes. ConclusionThere was a higher prevalence of bacterial organisms than fungal species among EE. Bacterial EE was associated with worse visual outcomes and higher enucleation rates than fungal EE. Multidrug resistance was prevalent among MRSA isolates. Older age and intravenous drug use may be factors associated with poor prognosis.
Journal Article
Ocular syphilis on the rise: a 10-year analysis from 2010 to 2020
2023
Purpose
The purpose of the study was to evaluate the incidence of ocular syphilis as well as diagnostic parameters, comorbidities, and visual outcomes over a 10-year time period in West Virginia.
Methods
A retrospective chart review included 25 eyes of 17 patients with ocular syphilis between 2010 and 2020.
Results
The incidence of systemic syphilis at a large tertiary referral center has increased from 27 cases in 2010 to 105 cases in 2020. Seventeen patients were identified with ocular syphilis. Bilaterality was present in 47.1% of cases. In this study, 70.6% of patients were male and 29.4% were female. The median age of presentation was 40.2 years (range 21–63). Panuveitis was the most common (60.0%) followed by isolated anterior uveitis (16.0%), chorioretinitis (12.0%), inner retinitis (4.0%), and papillitis (8.0%). Forty percent of patients had visual acuity worse than 20/400 on presentation. Post-treatment visual acuity improved in all patients. Rapid plasma reagin (RPR) and
Treponema pallidum
particle agglutination (TP-PA) tests were positive in 84.6% and 100% of cases, respectively. CSF venereal disease research laboratory (VDRL) was positive in 36.4%, CSF pleocytosis was present in 72.7%, and elevated CSF protein was observed in 81.8%. Human immunodeficiency virus (HIV) co-infection was present in 31.3%. A majority of patients experienced maculopapular rash and/or history of genital chancre. The anatomic classification of presenting uveitis (anterior, intermediate, posterior, and panuveitis) did not correlate with clinical variables including age, gender, HIV status, serologic test, presence of rash, or year of diagnosis (
p
> 0.05).
Conclusion
Ocular syphilis is becoming increasingly prevalent and can present with a variety of ocular findings; therefore, it should be considered in the differential diagnosis for patients with ocular inflammation. Visual prognosis is excellent with timely diagnosis and treatment.
Journal Article
Mortality risk associated with endophthalmitis in West Virginia
by
Desilets, Jeffrey
,
Hinkle, David M.
,
Fang, Wei
in
Diagnosis
,
Electronic health records
,
Electronic medical records
2021
Purpose
To explore how endophthalmitis presented from 2009 to 2019 in a West Virginia population particularly affected by the national opioid crisis. The analysis explores the relationship between the type of endophthalmitis and mortality, accounting for factors including age, gender, type of organism, and intravenous drug use (IVDU).
Methods
The electronic health record of West Virginia University (WVU) Medicine was queried for all patients managed for endophthalmitis from October 2009 to October 2019. For each of the included subjects, age, gender, history of IVDU, culture results, concomitant endocarditis, type of endophthalmitis, and the date of diagnosis were extracted. Mortality data were obtained from WVU’s electronic medical record, the Social Security Death Index, and public obituaries. Mortality results were represented by a Kaplan–Meier Survival curve following each patient for one year from the date of diagnosis. Results were analyzed using unadjusted and adjusted Cox Proportional Hazard models.
Results
One-year mortality was 14 out of 113 endogenous cases (12.4%) compared to 6 out of 173 exogenous cases (3.5%). Endogenous endophthalmitis cases had significantly higher mortality than exogenous ones within one year of diagnosis (
p
= 0.0034). The unadjusted Cox proportional hazards model revealed that the type of endophthalmitis (endogenous vs. exogenous) was the only variable with a significant impact on 1-year mortality with a hazard ratio of 3.78 (
p
= 0.01). However, the hazard ratio for endogenous infections rose to 10.91 (CI 3.544–33.595) when the other variables of age, gender, organism, and IVDU were controlled (
p
< 0.01). The Cox proportional hazard ratios for age group, gender, organism type, and history of IVDU were not significantly different when adjusted for all other variables.
Conclusion
Endogenous cases, which were significantly overrepresented in West Virginia, were associated with a significantly higher 1-year mortality rate than the exogenous ones. Age, gender, organism type, and history of IVDU have less, if any, modifying effect on mortality.
Journal Article
Curbside Consultation in Uveitis
2012
Are you looking for concise, practical answers to those questions that are often left unanswered by traditional references on uveitis? Are you seeking brief, evidence-based advice for the daily examination of patients? Curbside Consultation in Uveitis: 49 Clinical Questions provides quick and direct answers to the thorny questions most commonly posed during a 'curbside consultation' between experienced clinicians.
Dr. Stephen Foster has designed this unique reference in which uveitis specialists offer expert advice, preferences, and opinions on tough clinical questions commonly encountered by ophthalmologists, residents, and other health care professionals. The unique Q&A format provides quick access to current information related to uveitis with the simplicity of a conversation between two colleagues. Images, diagrams, and references are included to enhance the text and to illustrate clinical diagnoses and treatment plans.
Curbside Consultation in Uveitis: 49 Clinical Questions provides information basic enough for residents while also incorporating expert pearls that even high-volume ophthalmologists will appreciate. Refractive surgeons, general ophthalmologists, and residents alike will enjoy the user-friendly and casual format.
Some of the questions that are answered:
How do the results of the Systemic Immunosuppressive Therapy for Eye Disease (SITE) Cohort Study apply to the care of my patients with uveitis?
How should I evaluate and treat a patient with uveitis?
How should I treat macular edema in a patient with uveitis?
How should I treat a pregnant woman with macular threatening toxoplasmosis retinochoroiditis?
When should I refer a patient with uveitis to a uveitis specialist?
DJ-1 Expression Modulates Astrocyte-Mediated Protection Against Neuronal Oxidative Stress
by
Hinkle, David A.
,
Greenamyre, J. Timothy
,
Mullett, Steven J.
in
Animals
,
Antioxidants
,
Astrocytes - physiology
2013
DJ-1 deficiency is a cause of genetic Parkinson’s disease (PARK7 PD). In sporadic Parkinson’s disease (PD), however, DJ-1 is abundantly expressed in reactive astrocytes. This may represent a compensatory protective response. In initial support of this hypothesis, we have shown in vitro that DJ-1-overexpressing astrocytes protect neurons against rotenone-induced death. Rotenone, a pesticide linked to increased PD risk, can stimulate oxidative stress. This process is implicated in PD pathogenesis. Since DJ-1 can enhance antioxidant systems, we hypothesized that augmenting its expression in astrocytes would protect cocultured neurons against oxidative stress. We report here that DJ-1-overexpressing astrocytes were significantly more protective against rotenone-induced neuronal thiol oxidation than wild-type astrocytes in neuron–astrocyte cocultures. DJ-1-knockdown astrocytes, on the other hand, were significantly impaired in their capacity to protect neurons against thiol oxidation. Each of these findings was replicated using astrocyte-conditioned media on neuron-enriched cultures. Thus, DJ-1-modulated, astrocyte-released soluble factors must be involved in the mechanism. This is the first demonstration that the manipulation of a PD-causing gene in astrocytes affects their ability to protect neurons against oxidative stress.
Journal Article
Syphilitic retinitis presentations: punctate inner retinitis and posterior placoid chorioretinitis
2021
Purpose
To describe two distinct presentations of syphilitic fundus features in a series of patients with ocular syphilis.
Methods
This is a retrospective, interventional case series of 22 eyes from 16 serology confirmed cases. Clinical examination, fluorescein angiography, and optical coherence tomography were performed at presentation and following high-dose intravenous penicillin G.
Results
In our cohort, the mean age was 47.6 years (range 24–59 years) and 14 patients were male (87.5%), 11 patients were positive for human immunodeficiency virus (68.8%), and 6 had bilateral involvement (37.5%). Mean best-corrected visual acuity improved from 0.99 ± 0.79 logarithm of the minimal angle of resolution (LogMAR) at the time of presentation to 0.29 ± 0.36 LogMAR on final visit (
P
< 0.01). Posterior segment examinations in eyes with retinitis showed two distinct types (1) discrete, placoid lesions in the macula consistent with acute syphilitic posterior placoid chorioretinitis or (2) punctate inner retinitis with corresponding fluorescein pooling in a segmental pattern. These findings rapidly resolved after antibiotic therapy.
Conclusion
In the era of resurgence, ocular syphilis may present with two phenotypes of discrete retinal lesions. Recognition of the characteristic ocular features may help make the diagnosis and monitor treatment response.
Journal Article
Subepithelial Corneal Deposits Associated with Exemestane
2020
This is a case report of corneal deposits noted in a 69-year-old female patient taking the aromatase inhibitor, exemestane, after undergoing a mastectomy and chemotherapy for breast cancer. The patient presented to our eye clinic for a new-onset floater in one eye, and bilateral subepithelial opacities were found incidentally on exam. The patient completed a 5-year course of the medication shortly after her initial visit with us and was noted to have a slight improvement in the density of the opacities on a follow-up visit 3 months later. We believe these corneal changes were most likely secondary to exemestane. The effect of aromatase inhibitors on the eye deserves further exploration as an increasing number of patients are prescribed these medications.
Journal Article
Three-dimensional orientation tuning in macaque area V4
by
Hinkle, David A.
,
Connor, Charles E.
in
Animal Genetics and Genomics
,
Animals
,
Behavioral Sciences
2002
Tuning for the orientation of elongated, linear image elements (edges, bars, gratings), first discovered by Hubel and Wiesel, is considered a key feature of visual processing in the brain. It has been studied extensively in two dimensions (2D) using frontoparallel stimuli, but in real life most lines, edges and contours are slanted with respect to the viewer. Here we report that neurons in macaque area V4, an intermediate stage in the ventral (object-related) pathway of visual cortex, were tuned for 3D orientation—that is, for specific slants as well as for 2D orientation. The tuning for 3D orientation was consistent across depth position (binocular disparity) and position within the 2D classical receptive field. The existence of 3D orientation signals in the ventral pathway suggests that the brain may use such information to interpret 3D shape.
Journal Article