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1.
Article in English | MEDLINE | ID: mdl-38972465

ABSTRACT

PURPOSE: We aimed to determine if ultra-hypofractionated proton therapy delivered via stereotactic body proton therapy (SBPT) is non-inferior to conventionally fractionated proton therapy (CFPT) in patients with early prostate cancer. MATERIALS AND METHODS: This study was a multicenter, randomized, controlled, non-inferiority phase 3 trial that included patients with histologically confirmed low-risk prostate adenocarcinoma defined by Gleason score grouping 1, PSA <10 ng/mL, and clinical stage T1-2a N0 M0 according to AJCC 7th ed. Eligible participants were randomly assigned initially at a 1:1 ratio and later at a 2:1 ratio to SBPT (38 Gy in 5 fractions) or CFPT (79.2 Gy in 44 fractions). The primary endpoint was freedom from failure (FFF) at 2 years from the date of randomization. Non-inferiority for FFF was determined based on one-sided confidence intervals. Toxicities were compared at different time points using Fisher's Exact test. Health-related quality-of-life (HRQoL) was analyzed at different time points using a mixed-effects linear model. This trial is registered with ClinicalTrials.gov, NCT01230866, and is closed to accrual. RESULTS: Between December 10, 2010, and September 29, 2020, 144 patients were enrolled and 135 were randomly assigned (90 to the SBPT group and 45 to the CFPT group). The median follow-up was 5 years (IQR 3.9-5.2). The 2-year FFF was 100% for both groups, with the one-sided 5-year risk difference in FFF between groups reported as 2.63% (90% CI: -1.70%-6.96%), favoring the SBRT arm, thus fulfilling the pre-specified criteria for non-inferiority of SBPT compared to CFPT. Rates of gastrointestinal (GI) and genitourinary (GU) G2 and G3 toxicities did not differ significantly between groups but the the study was not powered to detect significant toxicity differences. Also, HRQoL metrics did not differ significantly between groups over the study median follow up. CONCLUSIONS: SBPT is non-inferior to CFPT regarding FFF, with similar long-term GU and GI toxicity rates and minimal impact in patient reported HRQoL over time.

2.
J Alzheimers Dis ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38995785

ABSTRACT

Alzheimer's disease (AD) accounts for most dementia cases, but we lack a complete understanding of the mechanisms responsible for the core pathology associated with the disease (e.g., amyloid plaque and neurofibrillary tangles). Inflammation has been identified as a key contributor of AD pathology, with recent evidence pointing towards Reelin dysregulation as being associated with inflammation. Here we describe Reelin signaling and outline existing research involving Reelin signaling in AD and inflammation. Research is described pertaining to the inflammatory and immunological functions of Reelin before we propose a mechanism through which inflammation renders Reelin susceptible to dysregulation resulting in the induction and exacerbation of AD pathology. Based on this hypothesis, it is predicted that disorders of both inflammation (including peripheral inflammation and neuroinflammation) and Reelin dysregulation (including disorders associated with upregulated Reelin expression and disorders of Reelin downregulation) have elevated risk of developing AD. We conclude with a description of AD risk in various disorders involving Reelin dysregulation and inflammation.

3.
Geriatr Orthop Surg Rehabil ; 15: 21514593241260097, 2024.
Article in English | MEDLINE | ID: mdl-38855405

ABSTRACT

Introduction: Open reduction and internal fixation (ORIF) is an established surgical procedure for distal humeral fractures; however, total elbow arthroplasty (TEA) has become an increasingly popular alternative for elderly patients with these injuries. Using a large sample of recent patient data, this study compares the rates of short-term complications between ORIF and TEA and evaluates complication risk factors. Methods: Patients who underwent primary TEA or ORIF from 2012 to 2021 were identified by Current Procedural Terminology codes in the American College of Surgeons National Surgical Quality Improvement Program database. Propensity score matching controlled for demographic and comorbid differences. The rates of 30-day postoperative complications were compared. Results: A total of 1539 patients were identified, with 1365 (88.7%) and 174 (11.3%) undergoing ORIF and TEA, respectively. Patients undergoing TEA were older on average (ORIF: 56.2 ± 19.8 years, TEA: 74.3 ± 11.0 years, P < .001). 348 patients were included in the matched analysis, with 174 patients in each group. TEA was associated with an increased risk for postoperative transfusion (OR = 6.808, 95% CI = 1.355 - 34.199, P = .020). There were no significant differences in any adverse event (AAE) between procedures (P = .259). A multivariate analysis indicated age was the only independent risk factor for the development of AAE across both groups (OR = 1.068, 95% CI = 1.011 - 1.128, P = .018). Conclusion: The risk of short-term complications within 30-days of ORIF or TEA procedures are similar when patient characteristics are controlled. TEA, however, was found to increase the risk of postoperative transfusions. Risks associated with increasing patient age should be considered prior to either procedure. These findings suggest that long-term functional outcomes can be prioritized in the management of distal humerus fractures.

4.
Adv Radiat Oncol ; 9(7): 101502, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38846486

ABSTRACT

Purpose: Low-dose total skin electron beam therapy (TSEBT) is a proven treatment for managing cutaneous T-cell lymphoma (CTCL) and Sezary syndrome with skin burden. We performed a retrospective comparison of response rates and time to progression for patients receiving low-dose TSEBT based on dose per fractionation, total dose, and stage. Methods and Materials: One hundred and ten patients with CTCL and Sezary syndrome were treated with 135 courses of low-dose (400-1500 cGy) TSEBT or subtotal skin electron therapy at multiple centers of a single institution between August 2003 and June 2023. Patients were stratified according to total dose, dose per fraction, and stage. Results: The median follow-up was 301 days (IQR, 141, 767). The median age at treatment was 69.9 years (range, 29.7-96.5). T-stage distribution was as follows: 3 (2.7%) T1, 74 (67.3%) T2, 16 (14.5%) T3, and 17 (15.5%) T4. American Joint Committee on Cancer eighth edition stage distribution was as follows: 3 (2.7%) IA, 53 (48.2%) IB, 3 (2.7%) IIA, 16 (14.5%) IIB, 8 (7.3%) IIIA, 19 (17.3%) IVA, and 8 (7.3%) IVB. There was no significant difference in disease distribution between patients treated with different fractionation schemes. The overall response rate was 89.6%. Forty-four courses (32.6%), 34 courses (25.2%), and 43 (31.9%) resulted in a complete, near-complete, and partial response, respectively. Fourteen courses (10.4%) resulted in no clinical response. For all patients, the median time to response was 43.0 days (IQR, 23.0-70). The median time to skin progression for all patients was 107.5 days (IQR, 67.8-233.5). Conclusions: This analysis demonstrated that CTCL patients treated with low-dose radiation therapy delivered over various fractionation schemes had similar overall response rates and median time to progression.

5.
Neuromuscul Disord ; 41: 20-23, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38865916

ABSTRACT

Inclusion body myositis is the commonest acquired myopathy in those over 50 years of age. Although it is classified as an idiopathic inflammatory myopathy and the most frequent finding on muscle biopsy in inclusion body myositis is an endomysial inflammatory infiltrate, it is clinically distinct from other myositis, including a lack of response to immunosuppressive medication. Neurogenic changes are commonly reported in inclusion body myositis and inflammatory changes are observed in muscle following neurogenic injury. The objective of our study was to explore whether neurogenic inflammation plays a role in the pathogenesis of inclusion body myositis, possibly explaining its resistance to immunosuppression. The number of mast cells and presence of neuropeptides, substance P and calcitonin gene-related peptide, were assessed in 48 cases of inclusion body myositis, 11 cases of steroid responsive myositis, two cases of focal myositis associated with neurogenic injury, and ten normal controls. The number of mast cells in inclusion body myositis focal and myositis associated to neurogenic injury were significantly greater than that observed in steroid responsive myositis. Our findings suggest that neurogenic inflammation mediated through mast cells may play a role in the pathogenesis of inclusion body myositis, and focal myositis associated to neurogenic injury, and thus, explain in some part its lack of response to immunosuppressive treatments.

6.
J Orthop Surg Res ; 19(1): 328, 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38825677

ABSTRACT

BACKGROUND: Although elective procedures have life-changing potential, all surgeries come with an inherent risk of reoperation. There is a gap in knowledge investigating the risk of reoperation across orthopaedics. We aimed to identify the elective orthopaedic procedures with the highest rate of unplanned reoperation and the reasons for these procedures having such high reoperation rates. METHODS: Patients in the NSQIP database were identified using CPT and ICD-10 codes. We isolated 612,815 orthopaedics procedures from 2018 to 2020 and identified the 10 CPT codes with the greatest rate of unplanned return to the operating room. For each index procedure, we identified the ICD-10 codes for the reoperation procedure and categorized them into infection, mechanical failure, fracture, wound disruption, hematoma or seroma, nerve pathology, other, and unspecified. RESULTS: Below knee amputation (BKA) (CPT 27880) had the highest reoperation rate of 6.92% (37 of 535 patients). Posterior-approach thoracic (5.86%) or cervical (4.14%) arthrodesis and cervical laminectomy (3.85%), revision total hip arthroplasty (5.23%), conversion to total hip arthroplasty (4.33%), and revision shoulder arthroplasty (4.22%) were among the remaining highest reoperation rates. The overall leading causes of reoperation were infection (30.1%), mechanical failure (21.1%), and hematoma or seroma (9.4%) for the 10 procedures with the highest reoperation rates. CONCLUSIONS: This study successfully identified the elective orthopaedic procedures with the highest 30-day return to OR rates. These include BKA, posterior thoracic and cervical spinal arthrodesis, revision hip arthroplasty, revision total shoulder arthroplasty, and cervical laminectomy. With this data, we can identify areas across orthopaedics in which revising protocols may improve patient outcomes and limit the burden of reoperations on patients and the healthcare system. Future studies should focus on the long-term physical and financial impact that these reoperations may have on patients and hospital systems. LEVEL OF CLINICAL EVIDENCE: IV.


Subject(s)
Elective Surgical Procedures , Operating Rooms , Orthopedic Procedures , Reoperation , Humans , Reoperation/statistics & numerical data , Orthopedic Procedures/methods , Orthopedic Procedures/statistics & numerical data , Female , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Male , Middle Aged , Risk Assessment , Databases, Factual , Aged
7.
Int J Radiat Oncol Biol Phys ; 119(1): 305-306, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38631742
8.
Article in English | MEDLINE | ID: mdl-38552775

ABSTRACT

There is an urgent need for novel antidepressants, given that approximately 30% of those diagnosed with depression do not respond adequately to first-line treatment. Additionally, monoaminergic-based antidepressants have a substantial therapeutic time-lag, often taking months to reach full therapeutic effect. Ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist is the only current effective rapid-acting antidepressant, demonstrating efficacy within hours and lasting up to two weeks with an acute dose. Reelin, an extracellular matrix glycoprotein, has demonstrated rapid-acting antidepressant-like effects at 24 h, however the exact timescale of these effects has not been investigated. To determine the short and long-term effects of reelin, female Long Evans rats (n = 120) underwent a chronic corticosterone (CORT; or vehicle) paradigm (40 mg/kg, 21 days). On day 21, rats were treated with reelin (3µg; i.v.), ketamine (10 mg/kg; i.p.), both reelin and ketamine (same doses), or vehicle (saline). Behavioural and biological effects were then evaluated at 1 h, 6 h, 12 h, and 1 week after treatment. The 1-week cohort continued CORT injections to ensure the effect of chronic stress was not lost. Individually, both reelin and ketamine significantly rescued CORT-induced behaviour and hippocampal reelin expression at all timepoints. Ketamine rescued a decrease in dendritic maturity as induced by CORT. Synergistic effects of reelin and ketamine appeared at 1-week, suggesting a potential additive effect of the antidepressant-like actions. Taken together, this study provides further support for reelin-based therapeutics to develop rapid-acting antidepressant.


Subject(s)
Corticosterone , Ketamine , Animals , Female , Rats , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Corticosterone/metabolism , Depression/drug therapy , Depression/chemically induced , Hippocampus/metabolism , Ketamine/pharmacology , Ketamine/therapeutic use , Rats, Long-Evans , Reelin Protein/pharmacology , Reelin Protein/therapeutic use
9.
Anticancer Res ; 44(4): 1491-1497, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38537978

ABSTRACT

BACKGROUND/AIM: Total skin electron beam therapy (TSEBT) is an effective treatment for managing cutaneous T-cell lymphoma (CTCL), but may result in unnecessary toxicity. With the production of a custom rolling shield holding a configurable stack of plastic slats to block uninvolved skin, we implemented a program for subtotal skin electron beam therapy (STSEBT). We report our preliminary experience with STSEBT vs. TSEBT to manage CTCL. PATIENTS AND METHODS: A retrospective review of 32 CTCL patients who were treated at a single institution between February 28th, 2017, and May 25th, 2022, was completed. Of these cases, seven patients received STSEBT and 25 received TSEBT. RESULTS: Thirty-two patients underwent a course of STSEBT or TSEBT. The median follow-up was 465 days and the median age at diagnosis was 70.8 years. Stage distribution was as follows: one (3%) IA, 16 (50%) IB, 6 (19%) IIB, two (6%) IIIA, five (16%) IVA, and two (6%) IVB. The overall response rate was 96%. For patients receiving TSEBT (n=25), three (12%), 10 (40%), and 11 (44%) had a CR, NCR, and PR, respectively. For the patients receiving STSEBT, four (57.1%), three (42.9%), and zero (0%) had a CR, NCR, and PR, respectively. There was one patient (4%) with no response. Cumulative incidence of progressive skin disease requiring additional electron therapy at three months was 21.1% [IQR=8.6, 51.5%], 36.8% [IQR=20, 68%] at six months, and 57.9% [IQR=38.5, 87.1%] at one year. Low rates of toxicities were recorded. CONCLUSION: This analysis demonstrated that treatment of CTCL patients with low disease burden with STSEBT results in similar overall response and time to progression compared to treatment with TSEBT.


Subject(s)
Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , Skin Neoplasms , Humans , Aged , Mycosis Fungoides/radiotherapy , Mycosis Fungoides/drug therapy , Mycosis Fungoides/pathology , Skin Neoplasms/radiotherapy , Skin Neoplasms/pathology , Electrons , Lymphoma, T-Cell, Cutaneous/radiotherapy , Lymphoma, T-Cell, Cutaneous/pathology , Skin/pathology
10.
Pract Radiat Oncol ; 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38325548

ABSTRACT

PURPOSE: The purpose of this investigation was to evaluate the clinical applicability of a commercial artificial intelligence-driven deep learning auto-segmentation (DLAS) tool on enhanced iterative cone beam computed tomography (iCBCT) acquisitions for intact prostate and prostate bed treatments. METHODS AND MATERIALS: DLAS models were trained using 116 iCBCT data sets with manually delineated organs at risk (bladder, femoral heads, and rectum) and target volumes (intact prostate and prostate bed) adhering to institution-specific contouring guidelines. An additional 25 intact prostate and prostate bed iCBCT data sets were used for model testing. Segmentation accuracy relative to a reference structure set was quantified using various geometric comparison metrics and qualitatively evaluated by trained physicists and physicians. These results were compared with those obtained for an additional DLAS-based model trained on planning computed tomography (pCT) data sets and for a deformable image registration (DIR)-based automatic contour propagation method. RESULTS: In most instances, statistically significant differences in the Dice similarity coefficient (DSC), 95% directed Hausdorff distance, and mean surface distance metrics were observed between the models, as the iCBCT-trained DLAS model outperformed the pCT-trained DLAS model and DIR-based method for all organs at risk and the intact prostate target volume. Mean DSC values for the proposed method were ≥0.90 for these volumes of interest. The iCBCT-trained DLAS model demonstrated a relatively suboptimal performance for the prostate bed segmentation, as the mean DSC value was <0.75 for this target contour. Overall, 90% of bladder, 93% of femoral head, 67% of rectum, and 92% of intact prostate contours generated by the proposed method were deemed clinically acceptable based on qualitative scoring, and approximately 63% of prostate bed contours required moderate or major manual editing to adhere to institutional contouring guidelines. CONCLUSIONS: The proposed method presents the potential for improved segmentation accuracy and efficiency compared with the DIR-based automatic contour propagation method as commonly applied in CBCT-based dose evaluation and calculation studies.

11.
J Palliat Med ; 27(2): 231-235, 2024 02.
Article in English | MEDLINE | ID: mdl-38301158

ABSTRACT

Background: Communication and interpersonal skills are essential medical components of oncology patient care. Patients and families rely on physicians for treatment, expertise, guidance, hope, meaning, and compassion throughout a life-threatening illness. A provider's inability to empathize with patients is linked to physician-related fatigue and burnout. Because oncology training programs focus on teaching evidence-based medicine and clinical acumen, little time may be dedicated to professional development and acquisition of interactive skills. Traditional communication courses typically include two components: formal, knowledge-based learning skills, which are gained from didactic lectures, and role-playing, which usually occurs in small groups. We report the implementation of a novel longitudinal communication curriculum for trainees in Oncology. Materials and Methods: At a single-center institution, an innovative communication curriculum titled "REFLECT" (Respect, Empathy, Facilitate Effective Communication, Listen, Elicit Information, Compassion, and Teach Others) was implemented for radiation oncology residents and medical oncology fellows to improve and refine physician/patient interactions. All oncology specialty residents and fellows were eligible to participate in this communication curriculum. The curriculum emphasized a reflective process to guide trainees through challenging scenarios. Results: Since October 2018, this comprehensive course consisted of quarterly (four hour) workshops comprising assigned reading, knowledge assessments, didactic lectures, expert guest lecturers, standardized patient simulations, role-playing, patient/expert panels, coaching, reflective writing, and debriefing/feedback sessions. The curriculum provided longitudinal communication training integrated with the learners' daily physician/patient encounters rather than occasional isolated experiences. Fifteen workshops have been completed. Each focused on navigating challenging situations with patients, loved ones, or colleagues. Conclusions: Future directions of the curriculum will entail improving the communication skills of oncology trainees and gathering communication improvement data to assess the program's success formally.


Subject(s)
Internship and Residency , Neoplasms , Humans , Education, Medical, Graduate , Medical Oncology/education , Curriculum , Communication , Physician-Patient Relations
12.
J Neonatal Perinatal Med ; 17(1): 147-152, 2024.
Article in English | MEDLINE | ID: mdl-38251067

ABSTRACT

We present a case of dichorionic-diamniotic twin females who developed hypoxemic respiratory failure. They were ultimately diagnosed by lung biopsy with alveolar capillary dysplasia with misalignment of pulmonary veins. This case highlights a practical approach to reaching a diagnosis in infants with suspected developmental lung disease.


Subject(s)
Persistent Fetal Circulation Syndrome , Pulmonary Alveoli , Pulmonary Veins , Female , Humans , Infant, Newborn , Lung , Persistent Fetal Circulation Syndrome/diagnosis , Persistent Fetal Circulation Syndrome/therapy , Pulmonary Alveoli/blood supply , Pulmonary Alveoli/abnormalities , Pulmonary Veins/diagnostic imaging
13.
Int J Radiat Oncol Biol Phys ; 118(4): 1049-1059, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-37914139

ABSTRACT

PURPOSE: Our aim was to report physician- and patient-reported outcomes of patients with localized breast cancer treated with moderate versus ultrahypofractionated whole breast irradiation (WBI) after breast-conserving surgery (BCS). METHODS AND MATERIALS: Between February 2018 and February 2020, patients with localized breast cancer (pT0-3 pN0-1 M0) were offered participation in a phase 3 randomized clinical trial assessing adjuvant moderate hypofractionation (MHF) to 40 Gy in 15 fractions versus ultrahypofractionation (UHF) to 25 Gy in 5 fractions after BCS, with an optional simultaneously integrated boost. Toxicities, cosmesis, and quality of life were assessed at baseline, end of treatment (EOT), and 3 months, 1 year, 2 years, and 3 years from irradiation using validated metric tools. RESULTS: One hundred seven patients were randomized to MHF (n = 54) or UHF (n = 53) adjuvant WBI. The median follow-up was 42.8 months. Grade 2 radiation dermatitis was experienced by 4 patients (7.4%) in the MHF arm and 2 patients (3.7%) in the UHF arm at EOT (P = .726). No grade 3 or higher toxicities were observed. Deterioration of cosmesis by physician assessment was observed in 2 (6.7%) patients treated in the UHF arm and 1 (1.9%) patient treated in the MHF arm at EOT (P = .534), whereas at 3 months, only 1 (1.8%) patient treated in the MHF arm demonstrated deterioration of cosmesis (P = .315). At EOT, 91% and 94% of patients reported excellent/good cosmesis among those treated with MHF and UHF regimens, respectively (P = .550). At 3 months, more patients within the MHF arm reported excellent/good cosmesis compared with those in the UHF arm (100% vs 91%; P = .030). However, the difference in patient-reported cosmesis disappeared at the 1-, 2-, and 3-year time points. CONCLUSIONS: UHF WBI showed similar treatment-related late toxicities and similar provider-scored cosmesis compared with MHF radiation in patients treated adjuvantly after BCS.


Subject(s)
Breast Neoplasms , Mastectomy, Segmental , Humans , Female , Radiotherapy, Adjuvant , Quality of Life , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Patient Reported Outcome Measures
14.
Int J Part Ther ; 10(1): 43-50, 2023.
Article in English | MEDLINE | ID: mdl-37823013

ABSTRACT

Unresectable mediastinal soft tissue sarcomas are often aggressive and associated with a poor prognosis. A 17-year-old male presented with progressive fatigue, shortness of breath, and heart palpitations secondary to an extensive mass involving the mediastinum and pericardium. He was treated with chemotherapy per protocol Children's Oncology Group Protocol ARST0332 and proton beam therapy to the involved mediastinum, pericardium, and heart. At the 5-year follow-up evaluation, he remained disease-free on surveillance imaging. An echocardiogram revealed a 55% to 60% left ventricular ejection fraction. Given the patient's extended survival, we present the oncologic rationale for treatment and considerations of late toxicity.

15.
BMC Med Educ ; 23(1): 776, 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37853366

ABSTRACT

This commentary provides evidence and expert opinion on effective relationships and communication strategies for trainee and graduate medical education leaders. The authors also argue that consistent communication and alignment of goals between trainee leadership and graduate medical education leadership are essential components of a successful collaboration that promotes trainee well-being.


Subject(s)
Communication , Education, Medical, Graduate , Humans , Leadership
16.
Brain Sci ; 13(8)2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37626560

ABSTRACT

Global and local biological motion processing are likely influenced by an observer's perceptual experience. Skilled athletes anticipating an opponent's movements use globally distributed motion information, while less skilled athletes focus on single kinematic cues. Published reports have demonstrated that attention can be primed globally or locally before perceptual tasks; such an intervention could highlight motion processing mechanisms used by skilled and less skilled observers. In this study, we examined skill differences in biological motion processing using attentional priming. Skilled (N = 16) and less skilled (N = 16) players anticipated temporally occluded videos of volleyball attacks after being primed using a Navon matching task while parietal EEG was measured. Skilled players were more accurate than less skilled players across priming conditions. Global priming improved performance in both skill groups. Skilled players showed significantly reduced alpha and beta power in the right compared to left parietal region, but brain activity was not affected by the priming interventions. Our findings highlight the importance of right parietal dominance for skilled performers, which may be functional for inhibiting left hemispheric local processing or enhancing visual spatial attention for dynamic visual scenes. Further work is needed to systematically determine the function of this pattern of brain activity during skilled anticipation.

18.
eNeuro ; 10(8)2023 08.
Article in English | MEDLINE | ID: mdl-37550058

ABSTRACT

Over the past decade, ketamine, an NMDA receptor antagonist, has demonstrated fast-acting antidepressant effects previously unseen with monoaminergic-based therapeutics. Concerns regarding psychotomimetic effects limit the use of ketamine for certain patient populations. Reelin, an extracellular matrix glycoprotein, has shown promise as a putative fast-acting antidepressant in a model of chronic stress. However, research has not yet demonstrated the changes that occur rapidly after peripheral reelin administration. To address this key gap in knowledge, male Long-Evans rats underwent a chronic corticosterone (CORT; or vehicle) paradigm (40 mg/kg, 21 d). On day 21, rats were then administered an acute dose of ketamine (10 mg/kg, i.p.), reelin (3 µg, i.v.), or vehicle. Twenty-four hours after administration, rats underwent behavioral or in vivo electrophysiological testing before killing. Immunohistochemistry was used to confirm changes in hippocampal reelin immunoreactivity. Lastly, the hippocampus was microdissected from fresh tissue to ascertain whole cell and synaptic-specific changes in protein expression through Western blotting. Chronic corticosterone induced a chronic stress phenotype in the forced swim test and sucrose preference test (SPT). Both reelin and ketamine rescued immobility and swimming, however reelin alone rescued latency to immobility. In vivo electrophysiology revealed decreases in hippocampal long-term potentiation (LTP) after chronic stress which was increased significantly by both ketamine and reelin. Reelin immunoreactivity in the dentate gyrus paralleled the behavioral and electrophysiological findings, but no significant changes were observed in synaptic-level protein expression. This exploratory research supports the putative rapid-acting antidepressant effects of an acute dose of reelin across behavioral, electrophysiological, and molecular measures.


Subject(s)
Ketamine , Rats , Male , Animals , Ketamine/pharmacology , Corticosterone/pharmacology , Corticosterone/metabolism , Rats, Long-Evans , Benchmarking , Hippocampus/metabolism , Antidepressive Agents/pharmacology , Antidepressive Agents/metabolism , Depression
19.
Cancers (Basel) ; 15(14)2023 Jul 22.
Article in English | MEDLINE | ID: mdl-37509376

ABSTRACT

In this study, we investigated whether radiomics features from pre-treatment positron emission tomography (PET) images could be used to predict disease progression in patients with HPV-positive oropharyngeal cancer treated with definitive proton or x-ray radiotherapy. Machine learning models were built using a dataset from Mayo Clinic, Rochester, Minnesota (n = 72) and tested on a dataset from Mayo Clinic, Phoenix, Arizona (n = 22). A total of 71 clinical and radiomics features were considered. The Mann-Whitney U test was used to identify the top 2 clinical and top 20 radiomics features that were significantly different between progression and progression-free patients. Two dimensionality reduction methods were used to define two feature sets (manually filtered or machine-driven). A forward feature selection scheme was conducted on each feature set to build models of increased complexity (number of input features from 1 to 6) and evaluate model robustness and overfitting. The machine-driven features had superior performance and were less prone to overfitting compared to the manually filtered features. The four-variable Gaussian Naïve Bayes model using the 'Radiation Type' clinical feature and three machine-driven features achieved a training accuracy of 79% and testing accuracy of 77%. These results demonstrate that radiomics features can provide risk stratification beyond HPV-status to formulate individualized treatment and follow-up strategies.

20.
Adv Radiat Oncol ; 8(6): 101289, 2023.
Article in English | MEDLINE | ID: mdl-37457824

ABSTRACT

Purpose: Purpose: Subtotal skin electron beam therapy may be an option for patients with cutaneous lymphoma receiving radiation therapy to treat large areas of their skin but may benefit from sparing specific areas that may have had previous radiation therapy, are of specific cosmetic concern, and/or show no evidence of disease. We report here on the design, implementation, and dosimetric characteristics of a reusable and transparent customizable shield for use with the large fields used to deliver total skin electron beam therapy at extended distance with a conventional linear accelerator. Methods and Materials: A shield was designed and manufactured consisting of acrylic blocks that can be mounted on a steel frame to allow patient-specific shielding. The dosimetry of the device was measured using radiochromic film. Results: The shield is easy to use and well-tolerated for patient treatment, providing minimal electron transmission through the shield with a sharp penumbra at the field edge, with no increase in x-ray dose. We report on the dosimetry of a commercial device that has been used to treat more than 30 patients to date. Conclusions: The customizable shield is well suited to providing patient-specific shielding for subtotal skin electron beam therapy.

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