Parkinson's Disease Mild Cognitive Impairment with MRI evidence of Cholinergic Nucleus 4 Degeneration: A New Subtype?

Subtyping Parkinson's disease with mild cognitive impairment (PD-MCI) could improve clinical trial design and personalized treatments. Cholinergic nucleus 4 (Ch4) volume has been linked to cognitive impairment severity and future decline in PD. This study investigates whether PD-MCI patients with MRI evidence of Ch4 degeneration have distinct clinical profiles and cognitive trajectories.

Neuropsychological Determinants of Impairment in Activities of Daily Living in Patients With Lewy Body Dementia.

Background Understanding the specific cognitive domains associated with activities of daily living (ADLs) impairment in Lewy body dementia (LBD) may help identify which targeted therapeutic interventions to pursue in future research. This study aimed to investigate the neuropsychological determinants of impairment in ADLs in LBD patients. Methods We conducted a cross-sectional study of LBD patients referred for a clinical neuropsychological evaluation within the Parkinson's Disease and Movement Disorders Center at Virginia Commonwealth University.

Optimizing Screening for Intrastriatal Interventions in Huntington's Disease Using Predictive Models.

Background: Intrastriatal delivery of potential therapeutics in Huntington's disease (HD) requires sufficient caudate and putamen volumes. Currently, volumetric magnetic resonance imaging is rarely done in clinical practice, and these data are not available in large research cohorts such as Enroll-HD.

Objective: The objective of this study was to investigate whether predictive models can accurately classify HD patients who exceed caudate and putamen volume thresholds required for intrastriatal therapeutic interventions.

Heterogeneity of weight loss and transcriptomic signatures in pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) is highly associated with cachexia and weight loss, which is driven by the tumour's effect on the body. Data are lacking on differences in these metrics based on PDAC anatomic location. We hypothesize that the primary tumour's anatomic region influences the prevalence and severity of unintentional weight loss.

MDA-9/Syntenin in the tumor and microenvironment defines prostate cancer bone metastasis.

Bone metastasis is a frequent and incurable consequence of advanced prostate cancer (PC). An interplay between disseminated tumor cells and heterogeneous bone resident cells in the metastatic niche initiates this process. () is a prometastatic gene expressed in multiple organs, including bone marrow-derived mesenchymal stromal cells (BM-MSCs), under both physiological and pathological conditions.

Dual Targeting of the PDZ1 and PDZ2 Domains of MDA-9/Syntenin Inhibits Melanoma Metastasis.

Genome-wide gene expression analysis and animal modeling indicate that melanoma differentiation associated gene-9 (mda-9, Syntenin, Syndecan binding protein, referred to as MDA-9/Syntenin) positively regulates melanoma metastasis. The MDA-9/Syntenin protein contains two tandem PDZ domains serving as a nexus for interactions with multiple proteins that initiate transcription of metastasis-associated genes. Although targeting either PDZ domain abrogates signaling and prometastatic phenotypes, the integrity of both domains is critical for full biological function.

Melatonin Supplementation for Cancer-Related Fatigue in Patients With Early Stage Breast Cancer Receiving Radiotherapy: A Double-Blind Placebo-Controlled Trial.

Background: Fatigue is common in patients undergoing radiotherapy (RT) and can significantly impact quality of life. Melatonin, a safe inexpensive natural supplement, may improve symptoms and attenuate the side effects of RT. The purpose of this randomized double-blind placebo-controlled phase III trial was to assess the effects of melatonin for preventing fatigue and other symptoms in patients with breast cancer undergoing RT.

Bilateral transversus abdominis plane and rectus sheath blocks with liposomal bupivacaine for patients undergoing robotic prostatectomy.

As robotic prostatectomy surgery becomes more prevalent, it is important to identify any regional techniques to optimize patient's recovery. We evaluated the effectiveness of bilateral transversus abdominis plane (TAP) and rectus sheath (RS) blocks with liposomal bupivacaine. We hypothesized that these blocks would reduce perioperative opioid use and pain scores.

Early termination in single-parameter model phase II clinical trial designs using decreasingly informative priors.

Background: To exchange the type of subjective Bayesian prior selection for assumptions more directly related to statistical decision making in clinician studies and trials, the decreasingly informative prior (DIP) is considered. We expand standard Bayesian early termination methods in one-parameter statistical models for Phase II clinical trials to include decreasingly informative priors (DIP). These priors are designed to reduce the chance of erroneously adapting trials too early by parameterize skepticism in an amount always equal to the unobserved sample size.

Cholinergic Nucleus 4 Degeneration and Cognitive Impairment in Isolated Rapid Eye Movement Sleep Behavior Disorder.

Background: Cholinergic nucleus 4 (Ch4) degeneration is associated with cognitive impairment in Parkinson's disease and dementia with Lewy bodies, but it is unknown if Ch4 degeneration is also present in isolated rapid eye movement sleep behavior disorder (iRBD).

Objective: The aim was to determine if there is evidence of Ch4 degeneration in patients with iRBD and if it is associated with cognitive impairment.

Methods: We analyzed the clinical and neuropsychological data of 35 iRBD patients and 35 age- and sex-matched healthy controls.

One Minute of EEG Data Provides Sufficient and Reliable Data for Identifying Lewy Body Dementia.

Objective: To determine the minimum duration of electroencephalography (EEG) data necessary to differentiate EEG features of Lewy body dementia (LBD), that is, dementia with Lewy bodies and Parkinson disease dementia, from non-LBD patients, that is, Alzheimer disease and Parkinson disease.

Methods: We performed quantitative EEG analysis for 16 LBD and 14 non-LBD patients. After artifact removal, a fast Fourier transform was performed on 90, 60, and thirty 2-second epochs to derive dominant frequency; dominant frequency variability; and dominant frequency prevalence.

Melanoma differentiation associated gene-9/syndecan binding protein promotes hepatocellular carcinoma.

Background And Aims: The oncogene Melanoma differentiation associated gene-9/syndecan binding protein (MDA-9/SDCBP) is overexpressed in many cancers, promoting aggressive, metastatic disease. However, the role of MDA-9 in regulating hepatocellular carcinoma (HCC) has not been well studied.

Approach And Results: To unravel the function of MDA-9 in HCC, we generated and characterized a transgenic mouse with hepatocyte-specific overexpression of MDA-9 (Alb/MDA-9).

Patient Survival With and Without Radiation Therapy for Early-Stage Diffuse Large B-Cell Lymphoma in the Era of PET and Rituximab.

Purpose: The benefit of radiation therapy (RT) becomes uncertain in the treatment of early stage diffuse large B-cell lymphoma (DLBCL) in the era of rituximab, positron emission topography (PET), and computed tomography (CT). We sought to retrospectively review modern patients with early stage I-II DLBCL treated with rituximab and staged by PET-CT to better define which patients benefit from consolidative RT.

Methods And Materials: Patients with early stage I-II DLBCL from 1998 to 2017 were reviewed coinciding with our institutional utilization of rituximab with the standard regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone and PET-CT.

Eligibility Criteria Perpetuate Disparities in Enrollment and Participation of Black Patients in Pancreatic Cancer Clinical Trials.

Purpose: Clinical trials determine safety and efficacy of cancer therapeutics and establish standards of care. Minority patient participation in cancer clinical trials is dismal. We aimed to determine the impact of eligibility criteria on disparities in pancreatic ductal adenocarcinoma (PDAC) clinical trial candidacy.

Target volume definition for staple line recurrences of non-small cell lung cancer.

Background: Staple line (SL) recurrences of non-small cell lung cancer (NSCLC) are commonly treated with radiotherapy (RT), but the target volume definition - whole SL versus focused on recurrence - is unclear. The aim of the study was to determine the appropriate target volume for RT of SL recurrences.

Materials And Methods: Twenty-two consecutive patients (20 stage I, 2 stage II) treated with salvage RT for SL recurrences were retrospectively analyzed.

Anticholinergic Medication Burden in Parkinson's Disease Outpatients.

Background: Individuals with Parkinson's disease (PD) may be especially vulnerable to future cognitive decline from anticholinergic medications.

Objective: To characterize anticholinergic medication burden, determine the co-occurrence of anticholinergic and cholinesterase inhibitors, and to assess the correlations among anticholinergic burden scales in PD outpatients.

Methods: We studied 670 PD outpatients enrolled in a clinic registry between 2012 and 2020.

Interprofessional Image Verification Workshop for Physician and Physics Residents: A Multi-Institutional Experience.

Purpose: Verification of patient position through pretreatment setup imaging is crucial in modern radiation therapy. As treatment complexity increases and technology evolves, physicist-physician collaboration becomes imperative for safe and successful radiation delivery. Despite the importance of both, residency programs lack formal interprofessional education (IPE) activities or structured training for image verification.

Statistical Modeling of Longitudinal Data with Non-ignorable Non-monotone Missingness with Semiparametric Bayesian and Machine Learning Components.

In longitudinal studies, outcomes are measured repeatedly over time and it is common that not all the patients will be measured throughout the study. For example patients can be lost to follow-up (monotone missingness) or miss one or more visits (non-monotone missingness); hence there are missing outcomes. In the longitudinal setting, we often assume the missingness is related to the unobserved data, which is non-ignorable.

PLK1 Induces Chromosomal Instability and Overrides Cell-Cycle Checkpoints to Drive Tumorigenesis.

Polo-like kinase 1 (PLK1) is an essential cell-cycle regulator that is frequently overexpressed in various human cancers. To determine whether Plk1 overexpression drives tumorigenesis, we established transgenic mouse lines that ubiquitously express increased levels of Plk1. High Plk1 levels were a driving force for different types of spontaneous tumors.

Moderately Hypofractionated Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost for Prostate Cancer: Five-Year Toxicity Results From a Prospective Phase I/II Trial.

Background: In this phase I/II trial, 5-year physician-assessed toxicity and patient reported quality of life data is reported for patients undergoing moderately hypofractionated intensity modulated radiation therapy (IMRT) for prostate cancer using a simultaneous integrated boost (SIB) and pelvic lymph node (LN) coverage.

Materials And Methods: Patients with T1-T2 localized prostate cancer were prospectively enrolled, receiving risk group based coverage of prostate ± seminal vesicles (SVs) ± pelvic lymph nodes (LNs). Low risk (LR) received 69.

Utilization of Multiparametric MRI of Prostate in Patients under Consideration for or Already in Active Surveillance: Correlation with Imaging Guided Target Biopsy.

This study sought to assess the value of multiparametric magnetic resonance image (mp-MRI) in patients with a prostate cancer (PCa) Gleason score of 6 or less under consideration for or already in active surveillance and to determine the rate of upgrading by target biopsy. Three hundred and fifty-four consecutive men with an initial transrectal ultrasound-guided (TRUS) biopsy-confirmed PCa Gleason score of 6 or less under clinical consideration for or already in active surveillance underwent mp-MRI and were retrospectively reviewed. One hundred and nineteen of 354 patients had cancer-suspicious regions (CSRs) at mp-MRI.

Effects of the recurrence pattern on patient survival following SABR for stage I lung cancer.

Information on the effect of the recurrence pattern on survival for stage I lung cancer following stereotactic ablative radiotherapy (SABR) is limited. The recurrence pattern was analyzed for 100 consecutive stage I non-small-cell lung cancer patients treated with SABR using predominantly 12 Gy × 4. Recurrences were classified as local, regional lymph nodes and distant.

Marginal Improvement in Survival Post-Heart Transplantation in Patients With Prior Left Ventricular Assist Device: A Temporal Analysis of United Network of Organ Sharing Registry.

Objective: An increasing number of patients undergoing heart transplantation are being bridged with left ventricular assist devices (LVADs). Bridge-to-transplantation (BTT) LVAD has improved wait list survival remarkably. Historically, post-heart transplantation survival in BTT-LVAD patients, however, has remained inferior to that of primary heart transplantation.

Phase 1 Study of Neoadjuvant Short-Course Radiation Therapy Concurrent With Infusional 5-Fluorouracil for the Treatment of Locally Advanced Rectal Cancer.

Purpose: To assess the safety and feasibility of neoadjuvant short-course radiation therapy (RT) concurrent with continuous infusion 5-fluorouracil (5-FU) for the treatment of locally advanced rectal cancer.

Methods And Materials: Patients with cT3-4 or N + rectal adenocarcinoma based on ultrasound or magnetic resonance imaging were prospectively enrolled in this study. Study treatment consisted of continuous infusion 5-FU combined with short-course RT (5 Gy x 5 fractions) followed by 4 cycles of mFOLFOX, total mesorectal excision (TME), and 6 cycles of adjuvant mFOLFOX.