Early detection of lung cancer in Czech high-risk asymptomatic individuals (ELEGANCE): A study protocol.

BACKGROUND: Lung cancer screening in high-risk population increases the proportion of patients diagnosed at a resectable stage. AIMS: To optimize the selection criteria and quality indicators for lung cancer screening by low-dose CT (LDCT) in the Czech population of high-risk individuals. To compare the influence of screening on the stage of lung cancer at the time of the diagnosis with the stage distribution in an unscreened population. To estimate the impact on life-years lost according to the stage-specific cancer survival and stage distribution in the screened population. To calculate the cost-effectiveness of the screening program. METHODS: Based on the evidence from large national trials - the National Lung Screening Trial in the USA (NLST), the NELSON study, the recent recommendations of the Fleischner society, the American College of Radiology, and I-ELCAP action group, we developed a protocol for a single-arm prospective study in the Czech Republic for the screening of high-risk asymptomatic individuals. The study commenced in August 2020. RESULTS: The inclusion criteria are: age 55 to 74 years; smoking: ≥30 pack-years; smoker or ex-smoker <15 years; performance status (0-1). The screening timepoints are at baseline and 1 year. The LDCT acquisition has a target CTDIvol ≤0.5mGy and effective dose ≤0.2mSv for a standard-size patient. The interpretation of findings is primarily based on nodule volumetry, volume doubling time (and related risk of malignancy). The management includes follow-up LDCT, contrast enhanced CT, PET/CT, tissue sampling. The primary outcome is the number of cancers detected at a resectable stage, secondary outcomes include the average cost per diagnosis of lung cancer, the number, cost, complications of secondary examinations, and the number of potentially important secondary findings. CONCLUSIONS: A study protocol for early detection of lung cancer in Czech high-risk asymptomatic individuals (ELEGANCE) study using LDCT has been described.

Relations of non-motor symptoms and dopamine transporter binding in REM sleep behavior disorder.

The aim of this study was to evaluate associations of motor and non-motor symptoms with dopamine transporter binding in prodromal stage of synucleinopathies. We examined 74 patients with idiopathic REM sleep behavior disorder (RBD), which is a prodromal synucleinopathy, and 39 controls using Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test (UPSIT), Farnsworth-Munsell 100 hue test, orthostatic test, Scales for Outcomes in PD-Autonomic, Beck depression inventory-II, State-Trait Anxiety Inventory, and video-polysomnography. Electromyographic muscle activity during REM sleep was quantified according to Sleep Innsbruck-Barcelona criteria. In 65 patients, dopamine transporter single-photon emission computed tomography (DAT-SPECT) imaging was performed, putaminal binding ratio was calculated and scans were classified as normal, borderline, or abnormal. Compared to controls, RBD patients had significantly more severe scores in all examined tests. Patients with abnormal DAT-SPECT had higher MDS-UPDRS motor score (p = 0.006) and higher prevalence of orthostatic hypotension (p = 0.008). Putaminal binding ratio was positively associated with UPSIT score (p = 0.03) and negatively associated with tonic (p = 0.003) and phasic (p = 0.01) muscle activity during REM sleep. These associations likely reflect simultaneous advancement of underlying pathology in substantia nigra and susceptible brainstem and olfactory nuclei in prodromal synucleinopathy.

Is fluorine-18-fluorocholine PET/CT suitable for the detection of skeletal involvement of multiple myeloma?

Our limited experience suggests that fluorine-18-fluorocholine (18F-FCH) may perform better in the detection of skeletal involvement by multiple myeloma compared to fluorine-18-fluorodeoxyglucose (18F-FDG) and that standard uptake ratio (SUR) might be considered in the semi-quantitative comparison of tracer uptake.

Neurological and Neurophysiological Findings in Workers with Chronic 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Intoxication 50 Years After Exposure.

The last eight survivors of 80 workers accidentally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during production of herbicides based on trichlorophenoxyacetic acid in 1965-1967 in a chemical factory were followed. All were men, mean age 72.4 ± 1.3 years. Their current median TCDD blood level was 112 (46-390) pg/g lipids. Neurological examination revealed central nervous system impairment in all individuals and signs of polyneuropathy in 87.5%, which was confirmed by a nerve conduction study (NCS) in 75%. A Lanthony test demonstrated acquired dyschromatopsia in 87.5% of the patients, with deterioration of mean colour confusion index (CCI) from 1.52 ± 0.39 in 2010 to 1.73 ± 0.41 in 2016. Single-photon emission computer tomography (SPECT) of the brain showed focal reduction of perfusion in various brain locations in all patients and worsening in six patients. Visual-evoked potentials (VEP) was abnormal in 62.6% of individuals. Most patients complained of psychological problems. The neuropsychological test battery showed most positive impairments in the Trail Making Test evaluating processing speed (average level in the range of mild neurocognitive impairment), which correlated with mean CCI (p < 0.05). CONCLUSION: Fifty years after exposure, blood levels of TCDD are still 10 times higher than the general population. NCS, VEP, Lanthony test and SPECT findings deteriorated from examination of these patients in 2004 and in 2010. The total of abnormal tests per patient in 2016 is very high. Minor differences among patients and their reduced count may explain why the number of impairments in 2016 does not correlate with TCDD blood level.

Prospective memory impairment in idiopathic REM sleep behavior disorder.

OBJECTIVE: The aim of the present study was to investigate if prospective memory (PM) is impaired in idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). RBD is a parasomnia characterized by dream enactment and by REM sleep without muscle atonia. iRBD is considered as the initial stage of neurodegeneration with pathological storage of alpha-synuclein. METHOD: Sixty iRBD patients with polysomnography-confirmed RBD without parkinsonism and dementia and 30 demographically matched normal controls (NC) were enrolled in the present study. Clinical assessment included Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), dopamine transporter single-photon emission computed tomography (DaT-SPECT) for imaging synapses of dopaminergic neurons in the striatum and a neuropsychological battery with embedded time-based and event-based PM measures. RESULTS: iRBD differed significantly from NC in event-based PM, a number of event-based failures to recall intention and total PM performance (all p < .001) but did not differ in time-based PM and recognition. PM did not contribute to impairment of instrumental activities of daily living in iRBD. Despite being preserved in iRBD in comparison to NC, time-based PM correlated significantly with dopaminergic neuronal loss measured by DaT-SPECT. CONCLUSIONS: We show evidence for a differential pattern of PM impairment in iRBD with severe impairment of event-based and concurrent preservation of time-based PM. We theorize that event-based PM impairment in iRBD is caused by severe impairment of retention and recognition mechanisms in episodic memory whereas time-based PM seems to be affected by reduced striatal dopaminergic synapses.

Whole-body low-dose computed tomography in multiple myeloma staging: Superior diagnostic performance in the detection of bone lesions, vertebral compression fractures, rib fractures and extraskeletal findings compared to radiography with similar radiation exposure.

The primary objective of the present prospective study was to compare the diagnostic performance of conventional radiography (CR) and whole-body low-dose computed tomography (WBLDCT) with a comparable radiation dose reconstructed using hybrid iterative reconstruction technique, in terms of the detection of bone lesions, skeletal fractures, vertebral compressions and extraskeletal findings. The secondary objective was to evaluate lesion attenuation in relation to its size. A total of 74 patients underwent same-day skeletal survey by CR and WBLDCT. In CR and WBLDCT, two readers assessed the number of osteolytic lesions at each region and stage according to the International Myeloma Working Group (IMWG) criteria. A single reader additionally assessed extraskeletal findings and their significance, the number of vertebral compressions and bone fractures. The radiation exposure was 2.7±0.9 mSv for WBLDCT and 2.5±0.9 mSv for CR (P=0.054). CR detected bone involvement in 127 out of 486 regions (26%; P<0.0001), confirmed by WBLDCT. CR underestimated the disease stage in 16% and overestimated it in 8% of the patients (P=0.0077). WBLDCT detected more rib fractures compared with CR (188 vs. 47; P<0.0001), vertebral compressions (93 vs. 67; P=0.010) and extraskeletal findings (194 vs. 52; P<0.0001). There was no correlation observed between lesion size (≥5 mm) and its attenuation (r=-0.006; P=0.93). The inter-observer agreement for the presence of osteolytic lesions was κ=0.76 for WBLDCT, and κ=0.55 for CR. The present study concluded that WBLDCT with hybrid iterative reconstruction technique demonstrates superiority to CR with an identical radiation dose in the detection of bone lesions, skeletal fractures, vertebral compressions and extraskeletal findings, which results in up- or downstaging in 24% patients according to the IMWG criteria. The attenuation of osteolytic lesions can be measured with the avoidance of the partial volume effect.

Fully automated classification of bone marrow infiltration in low-dose CT of patients with multiple myeloma based on probabilistic density model and supervised learning.

This paper presents a fully automated method for the identification of bone marrow infiltration in femurs in low-dose CT of patients with multiple myeloma. We automatically find the femurs and the bone marrow within them. In the next step, we create a probabilistic, spatially dependent density model of normal tissue. At test time, we detect unexpectedly high density voxels which may be related to bone marrow infiltration, as outliers to this model. Based on a set of global, aggregated features representing all detections from one femur, we classify the subjects as being either healthy or not. This method was validated on a dataset of 127 subjects with ground truth created from a consensus of two expert radiologists, obtaining an AUC of 0.996 for the task of distinguishing healthy controls and patients with bone marrow infiltration. To the best of our knowledge, no other automatic image-based method for this task has been published before.