Comparative efficacy of combined CTLA-4 and PD-1 blockade vs. PD-1 monotherapy in metastatic melanoma: a real-world study.

Background: In light of the substantial toxicity associated with combined CTLA-4 and PD-1 blockade (ipilimumab and nivolumab), we assessed its efficacy and safety against anti-PD-1 monotherapy (nivolumab or pembrolizumab) in patients with metastatic melanoma under real-world conditions.

Methods: We conducted a retrospective observational study involving 962 patients with stage IV metastatic melanoma who initiated adjuvant treatment between January 2017 and December 2021 across outpatient clinics in the United States. We adjusted for variables such as age, sex, ECOG performance status, comorbidity index, social deprivation index, metastatic sites, BRAF mutation status, and year of treatment.

Comparative Analysis of First-Line FOLFOX Treatment With and Without Anti-VEGF Therapy in Metastatic Colorectal Carcinoma: A Real-World Data Study.

Background: FOLFOX (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin) combined with or without anti-VEGF therapy represents one of the primary first-line treatment options for metastatic colorectal carcinoma (mCRC). However, there is limited comparative data on the impact of anti-VEGF therapy on treatment effectiveness, survival outcomes, and tumor location.

Methods: This retrospective, comparative study utilized data from the AIM Cancer Care Quality Program and commercially insured patients treated at medical oncology clinics in the US.

Network abnormalities among non-manifesting Parkinson disease related LRRK2 mutation carriers.

Non-manifesting carriers (NMC) of the G2019S mutation in the LRRK2 gene represent an "at risk" group for future development of Parkinson's disease (PD) and have demonstrated task related fMRI changes. However, resting-state networks have received less research focus, thus this study aimed to assess the integrity of the motor, default mode (DMN), salience (SAL), and dorsal attention (DAN) networks among this unique population by using two different connectivity measures: interregional functional connectivity analysis and Dependency network analysis (D NA). Machine learning classification methods were used to distinguish connectivity between the two groups of participants.

Cerebral Imaging Markers of GBA and LRRK2 Related Parkinson's Disease and Their First-Degree Unaffected Relatives.

Cerebral atrophy has been detected in patients with Parkinson's disease (PD) both with and without dementia, however differentiation based on genetic status has thus far not yielded robust findings. We assessed cortical thickness and subcortical volumes in a cohort of PD patients and healthy controls carriers of the G2019S mutation in the LRRK2 gene and the common GBA mutations, in an attempt to determine whether genetic status influences structural indexes. Cortical thickness and subcortical volumes were computed and compared between six groups of participants; idiopathic PD, GBA-PD, LRRK2-PD, non-manifesting non-carriers (NMNC), GBA-non-manifesting carriers (NMC) and LRRK2-NMC utilizing the FreeSurfer software program.

Disparate effects of training on brain activation in Parkinson disease.

Objective: To compare the effects of 2 forms of exercise, i.e., a 6-week trial of treadmill training with virtual reality (TT + VR) that targets motor and cognitive aspects of safe ambulation and a 6-week trial of treadmill training alone (TT), on brain activation in patients with Parkinson disease (PD).

Subcortical Volumes Differ in Parkinson's Disease Motor Subtypes: New Insights into the Pathophysiology of Disparate Symptoms.

Objectives: Patients with Parkinson's disease (PD) can be classified, based on their motor symptoms into the Postural Instability Gait Difficulty (PIGD) subtype or the Tremor Dominant (TD) subtype. Gray matter changes between the subtypes have been reported using whole brain Voxel-Based Morphometry (VBM), however, the evaluation of subcortical gray matter volumetric differences between these subtypes using automated volumetric analysis has only been studied in relatively small sample sizes and needs further study to confirm that the negative findings were not due to the sample size. Therefore, we aimed to evaluate volumetric changes in subcortical regions and their association with PD motor subtypes.

Alterations in conflict monitoring are related to functional connectivity in Parkinson's disease.

Patients with Parkinson's disease (PD) have difficulties in executive functions including conflict monitoring. The neural mechanisms underlying these difficulties are not yet fully understood. In order to examine the neural mechanisms related to conflict monitoring in PD, we evaluated 35 patients with PD and 20 healthy older adults while they performed a word-color Stroop paradigm in the MRI.

Dependency Network Analysis (DEPNA) Reveals Context Related Influence of Brain Network Nodes.

Communication between and within brain regions is essential for information processing within functional networks. The current methods to determine the influence of one region on another are either based on temporal resolution, or require a predefined model for the connectivity direction. However these requirements are not always achieved, especially in fMRI studies, which have poor temporal resolution.

Fall risk is associated with amplified functional connectivity of the central executive network in patients with Parkinson's disease.

Falls are debilitating problems that markedly impact the health-related quality of life of many patients with Parkinson's disease (PD). Numerous studies point to the role of executive function and attention in falls; however, the brain mechanisms underlying these relationships are less clear. Here, we aim to evaluate the brain mechanisms underlying the role of executive function in falls.

Gray matter atrophy and freezing of gait in Parkinson's disease: Is the evidence black-on-white?

Objectives: The pathophysiology underlying freezing of gait (FOG) in Parkinson's disease (PD) is poorly understood. We tested whether gray matter (GM) atrophy contributes to FOG in PD.

Methods: Voxel-based morphometry quantified GM atrophy in 106 patients who were classified as freezers (n = 30) or nonfreezers (n = 76).

Gray matter atrophy distinguishes between Parkinson disease motor subtypes.

Objective: To assess differences in gray matter (GM) atrophy between 2 Parkinson disease (PD) subtypes: the tremor dominant (TD) subtype and the postural instability gait difficulty (PIGD) subtype.

Methods: Patients were classified as belonging to the predominately PIGD (n = 30) or predominately TD (n = 29) subtype. Voxel-based morphometry was used to compare GM in these 2 subtypes and to evaluate correlations between predefined regions of interest and the degree of symptoms.

White matter hyperintensities in Parkinson's disease: do they explain the disparity between the postural instability gait difficulty and tremor dominant subtypes?

Background: Brain white matter hyperintensities (WMHs) commonly observed on brain imaging of older adults are associated with balance and gait impairment and have also been linked to cognitive deficits. Parkinson's disease (PD) is traditionally sub-classified into the postural instability gait difficulty (PIGD) sub-type, and the tremor dominant (TD) sub-type. Considering the known association between WMHs and axial symptoms like gait disturbances and postural instability, one can hypothesize that WMHs might contribute to the disparate clinical sub-types of patients with PD.

Neural correlates of executive functions in healthy G2019S LRRK2 mutation carriers.

Introduction: The G2019S mutation in the leucine rich repeat kinase 2 (LRRK2) gene is prevalent among Ashkenazi Jewish patients with Parkinson's disease (PD). Cognitive deficits are common in early stage PD. We aimed to characterize the effect of the G2019S mutation on neural mechanisms of executive function processing by testing whether healthy mutation carriers who are an "at risk" population for the future development of PD differed from non-carriers on an functional magnetic resonance imaging (fMRI) Stroop interference task.

Enhanced functional synchronization of medial and lateral PFC underlies internally-guided action planning.

Actions are often internally guided, reflecting our covert will and intentions. The dorsomedial prefrontal cortex, including the pre-Supplementary Motor Area (pre-SMA), has been implicated in the internally generated aspects of action planning, such as choice and intention. Yet, the mechanism by which this area interacts with other cognitive brain regions such as the dorsolateral prefrontal cortex, a central node in decision-making, is still unclear.