48 research outputs found
Evaluation of progressive visual dysfunction and retinal degeneration in patients with parkinsonâs disease
PURPOSE. To quantify changes in visual function parameters and in the retinal nerve fiber layer and macular thickness over a 5-year period in patients with Parkinsonâs disease (PD). METHODS. Thirty patients with PD and 30 healthy subjects underwent a complete ophthalmic evaluation, including assessment of visual acuity, contrast sensitivity vision, color vision, and retinal evaluation with spectral-domain optical coherence tomography (SD-OCT). All subjects were reevaluated after 5 years to quantify changes in visual function parameters, the retinal nerve fiber layer, and macular thickness. Association between progressive ophthalmologic changes and disease progression was analyzed. RESULTS. Changes were detected in visual function parameters and retinal nerve fiber layer thickness in patients compared with controls. Greater changes were found during the follow-up in the PD group than healthy subjects in visual acuity, contrast sensitivity, Lanthony color test (P < 0.016), in superotemporal and temporal retinal nerve fiber layer sectors (P < 0.001), and in macular thickness (all sectors except inner superior and inner inferior sectors, P < 0.001). Progressive changes in the retinal nerve fiber layer were associated with disease progression (r = 0.389, P = 0.028). CONCLUSIONS. Progressive visual dysfunction, macular thinning, and axonal loss can be detected in PD. Analysis of the macular thickness and the retinal nerve fiber layer by SD-OCT can be useful for evaluating Parkinsonâs disease progression
Optical Coherence Tomography as a Biomarker for Diagnosis, Progression, and Prognosis of Neurodegenerative Diseases
Neurodegenerative diseases present a current challenge for accurate diagnosis and for providing precise prognostic information. Developing imaging biomarkers for multiple sclerosis (MS), Parkinson disease (PD), and Alzheimer''s disease (AD) will improve the clinical management of these patients and may be useful for monitoring treatment effectiveness. Recent research using optical coherence tomography (OCT) has demonstrated that parameters provided by this technology may be used as potential biomarkers for MS, PD, and AD. Retinal thinning has been observed in these patients and new segmentation software for the analysis of the different retinal layers may provide accurate information on disease progression and prognosis. In this review we analyze the application of retinal evaluation using OCT technology to provide better understanding of the possible role of the retinal layers thickness as biomarker for the detection of these neurodegenerative pathologies. Current OCT analysis of the retinal nerve fiber layer and, specially, the ganglion cell layer thickness may be considered as a good biomarker for disease diagnosis, severity, and progression
Primary Extra-gastrointestinal Stromal Tumor of Retroperitoneum
Background Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. More rarely neoplasms with histology and immunohistochemistry similar to GISTs may occur outside the gastrointestinal tract (omentum, mesentery and retroperitoneum) and are so-called Extra-gastrointestinal Stromal Tumors (EGISTs). EGISTs arising in the retroperitoneum are extremely rare: to date, only 58 cases have been reported in the literature. Case Report We herein report a case of a primary EGIST of the retroperitoneum surgically treated. The pre-operative radiological evaluation showed a retroperitoneal mass, placed in left paravertebral region. Results Morphological and immunohistochemical features led to a diagnosis of extra-gastrointestinal stromal tumor (intermediate-low risk form). Conclusions As a result of the rarity of reports of primary EGISTs of retroperitoneum we need to analyze the data of reported cases in order to gain a better understanding about the pathogenesis, prognosis and optimal treatment of this disease
Ostertagia spp., rumen fluke and liver fluke single- and poly-infections in cattle: an abattoir study of prevalence and production impacts in England and Wales
This study aims at investigating the occurrence, risk factors and production impacts on beef carcassparameters of three of the most important cattle helminth infections in England and Wales. Abomasa, reticulorumens and livers from healthy cattle were collected and examined post-mortem quarterly over a one year period in an abattoir in South-West England. Specific viscera from 974 cattle were collected,examined and scored for Ostertagia spp., adult rumen fluke and liver fluke lesions/presence. A total of89%, 25% and 29% of the carcasses had lesions/presence of Ostertagia spp., rumen fluke and liver fluke, respectively, and 39% had presence of helminth co-infection. Animal demographic and carcass parameters associated with helminth infections were investigated using multi level multinomial and multilevel linear mixed models respectively. After adjusting for other factors, significant differences in the distribution of helminth infections were observed among cattle by type of breed, animal category (cow, heifer, steer and young bull), age, season and concurrent helminth infections. Compared to carcasses free of helminths, carcasses presenting solely Ostertagia Spp. lesions or adult rumen fluke had significantly lower cold carcass weight (coef.: â30.58 [â50.92;â10.24] and â50.34 [â88.50;â12.18]) and fat cover-age (coef.: â3.28 [â5.56;â1.00] and â5.49 [â10.28;â0.69]) and carcasses presenting solely liver flukelesions had significantly lower conformation grade (coef.: â3.65 [â6.98;â0.32]). Presence of helminth poly-infections was negatively associated with cold carcass weight
Nivolumab in Advanced Hepatocellular Carcinoma: Safety Profile and Select Treatment-Related Adverse Events From the CheckMate 040 Study
Background. CheckMate 040 assessed the efficacy and safety
of nivolumab in patients with advanced hepatocellular carcinoma (HCC). Understanding the safety profile of nivolumab is
needed to support the management of treatment-related
adverse events (TRAEs). This analysis assessed the safety
of nivolumab monotherapy in the phase I/II, open-label
CheckMate 040 study.
Materials and Methods. Select TRAEs (sTRAEs; TRAEs with
potential immunologic etiology requiring more frequent
monitoring) occurring between first dose and 30 days after
last dose were analyzed in patients in the dose-escalation
and -expansion phases. Time to onset (TTO), time to resolution (TTR), and recurrence of sTRAEs were assessed, and
the outcome of treatment with immune-modulating medication (IMM) was evaluated.
Results. The analysis included 262 patients. The most common sTRAE was skin (35.5%), followed by gastrointestinal
(14.5%) and hepatic (14.1%) events; the majority were grade
1/2, with 10.7% of patients experiencing grade 3/4 events.
One patient had grade 5 pneumonitis. Median (range) TTO
ranged from 3.6 (0.1â59.9) weeks for skin sTRAEs to 47.6
(47.1â48.0) weeks for renal sTRAEs. Overall, 68% of sTRAEs
resolved, with median (range) TTR ranging from 3.7
(0.1â123.3+) weeks for gastrointestinal sTRAEs to 28.4
(0.1â79.1) weeks for endocrine sTRAEs. Most gastrointestinal
and all hepatic events resolved with treatment in accordance
with established toxicity management algorithms. In
57 patients (40%), sTRAEs were managed with IMM.
Reoccurrence of sTRAEs was uncommon following rechallenge
with nivolumab.
Conclusion. Nivolumab demonstrated a manageable safety
profile in this analysis of patients with advanced HCC. A
majority of sTRAEs resolved with treatment
Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: updated time-to-events results and prognostic factors for time to progression
New treatment options offering enhanced activity in elderly, newly diagnosed patients with multiple
myeloma are required. One strategy is to combine melphalan and prednisone with novel agents.
We previously reported an 89% response rate, including 32% complete responses and 11% near
complete responses, in our phase 1/2 study of bortezomib plus melphalan and prednisone (VMP)
in 60 newly diagnosed multiple myeloma patients with a median age of 75 years. Here, we report
updated time-to-events data and the impact of poor prognosis factors on outcome
Color superconductivity, Z_N flux tubes and monopole confinement in deformed N=2* super Yang-Mills theories
We study the Z_N flux tubes and monopole confinement in deformed N=2* super
Yang-Mills theories. In order to do that we consider an N=4 super Yang-Mills
theory with an arbitrary gauge group G and add some N=2, N=1 and N=0
deformation terms. We analyze some possible vacuum solutions and phases of the
theory, depending on the deformation terms which are added. In the Coulomb
phase for the N=2* theory, G is broken to U(1)^r and the theory has monopole
solutions. Then, by adding some deformation terms, the theory passes to the
Higgs or color superconducting phase, in which G is broken to its center C_G.
In this phase we construct the Z_N flux tubes ansatz and obtain the BPS string
tension. We show that the monopole magnetic fluxes are linear integer
combinations of the string fluxes and therefore the monopoles can become
confined. Then, we obtain a bound for the threshold length of the
string-breaking. We also show the possible formation of a confining system with
3 different monopoles for the SU(3) gauge group. Finally we show that the BPS
string tensions of the theory satisfy the Casimir scaling law.Comment: 18 pages, 2 figures, typo corrections. Version to appear in Phys.
Rev.
Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours : results from the COPPADIS cohort
The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose
New insights into the genetic etiology of Alzheimer's disease and related dementias.
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele