Parkinson's disease laterality: a 11C-PE2I PET imaging study

Asymmetry of striatal dopaminergic deficits and motor symptoms is a typical characteristic of idiopathic Parkinson’s disease (PD). This study aims to characterise the trend of asymmetry in moderate-stage PD. We performed a 19-month longitudinal study in 27 patients with PET-CT imaging and appropriate clinical assessments. 11C-PE2I non-displaceable binding potential (BPND) was calculated bilaterally for the striatum at baseline and follow-up to estimate the in vivo density of striatal dopamine transporters (DAT). Changes in striatal 11C-PE2I BPND over time were more prominent in the ipsilateral as compared to contralateral side. Changes in MDS-UPDRS-III (motor component of the Movement Disorders Society Unified PD Rating Scale) were not different between the clinically most and least affected body sides. Our data support that the asymmetry in striatal dopaminergic degeneration becomes less prominent in moderate-stage PD. In contrast, during the above period, the asymmetry of motor symptoms was maintained between the clinically most and least affected body sides

Dissociable effects of age and Parkinson’s disease on instruction-based learning

The cognitive deficits associated with Parkinson’s disease vary across individuals and change across time, with implications for prognosis and treatment. Key outstanding challenges are to define the distinct behavioural characteristics of this disorder and develop diagnostic paradigms that can assess these sensitively in individuals. In a previous study, we measured different aspects of attentional control in Parkinson’s disease using an established fMRI switching paradigm. We observed no deficits for the aspects of attention the task was designed to examine; instead those with Parkinson’s disease learnt the operational requirements of the task more slowly. We hypothesized that a subset of people with early-to-mid stage Parkinson’s might be impaired when encoding rules for performing new tasks. Here, we directly test this hypothesis and investigate whether deficits in instruction-based learning represent a characteristic of Parkinson’s Disease. Seventeen participants with Parkinson’s disease (8 male; mean age: 61.2 years), 18 older adults (8 male; mean age: 61.3 years) and 20 younger adults (10 males; mean age: 26.7 years) undertook a simple instruction-based learning paradigm in the MRI scanner. They sorted sequences of coloured shapes according to binary discrimination rules that were updated at two-minute intervals. Unlike common reinforcement learning tasks, the rules were unambiguous, being explicitly presented; consequently, there was no requirement to monitor feedback or estimate contingencies. Despite its simplicity, a third of the Parkinson’s group, but only one older adult, showed marked increases in errors, 4 SD greater than the worst performing young adult. The pattern of errors was consistent, reflecting a tendency to misbind discrimination rules. The misbinding behaviour was coupled with reduced frontal, parietal and anterior caudate activity when rules were being encoded, but not when attention was initially oriented to the instruction slides or when discrimination trials were performed. Concomitantly, Magnetic Resonance Spectroscopy showed reduced gamma-Aminobutyric acid levels within the mid-dorsolateral prefrontal cortices of individuals who made misbinding errors. These results demonstrate, for the first time, that a subset of early-to-mid stage people with Parkinson’s show substantial deficits when binding new task rules in working memory. Given the ubiquity of instruction-based learning, these deficits are likely to impede daily living. They will also confound clinical assessment of other cognitive processes. Future work should determine the value of instruction-based learning as a sensitive early marker of cognitive decline and as a measure of responsiveness to therapy in Parkinson's disease

Global ecological predictors of the soil priming effect.

Identifying the global drivers of soil priming is essential to understanding C cycling in terrestrial ecosystems. We conducted a survey of soils across 86 globally-distributed locations, spanning a wide range of climates, biotic communities, and soil conditions, and evaluated the apparent soil priming effect using 13C-glucose labeling. Here we show that the magnitude of the positive apparent priming effect (increase in CO2 release through accelerated microbial biomass turnover) was negatively associated with SOC content and microbial respiration rates. Our statistical modeling suggests that apparent priming effects tend to be negative in more mesic sites associated with higher SOC contents. In contrast, a single-input of labile C causes positive apparent priming effects in more arid locations with low SOC contents. Our results provide solid evidence that SOC content plays a critical role in regulating apparent priming effects, with important implications for the improvement of C cycling models under global change scenarios

Performance of Screening Strategies for Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease: Results from the ENEIDA Registry of GETECCU

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-gamma-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18-20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50-0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66-0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20-22%] vs. 14% [95% CI 13-16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM

Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and severe COVID-19: a study of ERIC, the European Research Initiative on CLL

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. The aim of this study was to assess the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. METHODS: This is a retrospective multicenter study conducted by ERIC, the European Research Initiative on CLL, including patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. The COVID-19 diagnosis was confirmed by the real-time polymerase chain reaction (RT-PCR) assay for SARS-CoV-2 on nasal or pharyngeal swabs. Severe cases of COVID-19 were defined by hospitalization and the need of oxygen or admission into ICU. Development and type of thrombotic events, presence and severity of bleeding complications were reported during treatment for COVID-19. Bleeding events were classified using ISTH definition. STROBE recommendations were used in order to enhance reporting. RESULTS: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 511 were defined as having severe COVID: 162 were admitted to the ICU while 349 received oxygen supplementation outside the ICU. Most patients (90.5%) were receiving thromboprophylaxis. During COVID-19 treatment, 11.1% developed a thromboembolic event, while 5.0% experienced bleeding. Thrombosis developed in 21.6% of patients who were not receiving thromboprophylaxis, in contrast to 10.6% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (8.1% vs. 3.8%, respectively) and in elderly. In multivariate analysis, peak D-dimer level and C-reactive protein to albumin ratio were poor prognostic factors for thrombosis occurrence (OR?=?1.022, 95%CI 1.007?1.038 and OR?=?1.025, 95%CI 1.001?1.051, respectively), while thromboprophylaxis use was protective (OR?=?0.199, 95%CI 0.061?0.645). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR?=?1.062, 95%CI 1.017-1.109 and OR?=?2.438, 95%CI 1.023-5.813, respectively). CONCLUSIONS: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration

Nigral iron and neuromelanin studies in Parkinson´s disease

Parkinson’s disease (PD) a neurodegenerative condition characterized by the reduction of the pigmented dopaminergic neurons of the substantia nigra pars compacta (SNc) and the loss of the dopaminergic striatal terminals which in turn result in the cardinal motor symptoms including bradykinesia, rigidity and tremor. Iron plays a deleterious role in the pathophysiology of PD due to the generation of reactive oxidative species that leads to oxidative stress and neurodegeneration. In addition neuromelanin is a complex pigment contained in the dopaminergic neurons of the SNc that plays a toxic role in pro-oxidative conditions such as PD. Magnetic resonance imaging (MRI) is a widely available nonionising technique allowing the study of structural properties of the SN such as iron deposition or neuromelanin pigmentation load in PD. In this thesis I have used state of the art neuroimaging to assess nigral iron accumulation and nigral depigmentation in PD, the correlation between neuromelanin decline and nigrostriatal terminal loss, and the potential clinical use of an iron chelation to improve clinical symptoms. The main findings of this thesis are as follows: A) Increased nigral iron accumulation in PD displays an ascendant stratification according to clinical severity at baseline and it is associated with bradykinesia and rigidity symptoms in cross-sectional and longitudinal settings. B) Nigral depigmentation in PD shows a descendant stratification according to disease duration at baseline and displays significant associations with motor severity at baseline and with bradykinesia at follow-up visits. C) The pattern of nigral pigmentation loss shows a ventro-medial pattern and there was a significant correlation between this loss and nigrostriatal terminals decline in the most affected side, but not in the least affected side. D) Finally, iron chelation with deferiprone in PD shows a trend of motor improvement after six months of treatment being optimally monitored with iron-sensitive MR imaging techniques. The results presented in this thesis support the application of multimodal imaging protocols to further understand the dopaminergic pathophysiology of PD and their usefulness for monitoring the progression of the disease.Open Acces

Iron metabolism and its detection through MRI in parkinsonian disorders: a systematic review

Iron deposition in the brain normally increase with age, but its accumulation in certain regions is ob- served in a number of neurodegenerative diseases in- cluding Parkinson’s disease (PD) and other parkinson- isms. Whether iron overload leads to dopaminergic neu- ronal death in the SN of PD patients or is instead sim- ply a by-product of the neurodegenerative progression is still yet to be ascertained. Magnetic resonance imaging (MRI) is a non-invasive method to assess brain iron content in PD patients. In PD, accurate radiologic visu- alization of basal ganglia is required. Deep gray matter nuclei are well presented in T2- and T2*-weighted im- ages. T2*-weighted gradient-echo (GRE) is widely used to assess calcifications and also for iron detection. On the other hand, new methods specifically designed for detecting iron-induced susceptibility differences can be further improved by sequences like susceptibility- weighted imaging (SWI). In the present review, we aim to summarize the available data on brain iron de- position in PD

Is chelation therapy a potential treatment for Parkinson’s disease?

Iron loading in some brain regions occurs in Parkinson’s Disease (PD), and it has been considered that its removal by iron chelators could be an appropriate therapeutic approach. Since neuroinflammation with microgliosis is also a common feature of PD, it is possible that iron is sequestered within cells as a result of the “anaemia of chronic disease” and remains unavailable to the chelator. In this review, the extent of neuroinflammation in PD is discussed together with the role played by glia cells, specifically microglia and astrocytes, in controlling iron metabolism during inflammation, together with the results of MRI studies. The current use of chelators in clinical medicine is presented together with a discussion of two clinical trials of PD patients where an iron chelator was administered and showed encouraging results. It is proposed that the use of anti‐inflammatory drugs combined with an iron chelator might be a better approach to increase chelator efficacy