Algorithm to improve the diagnosis of paraneoplastic neurological syndromes associated with SOX1 antibodies

Cell-based assay; Paraneoplastic neurological syndromes; Small-cell lung cancerAssaig basat en cèl·lules; Síndromes neurològiques paraneoplàstiques; Càncer de pulmó de cèl·lules petitesEnsayo basado en células; Síndromes neurológicos paraneoplásicos; Cáncer de pulmón de células pequeñasSOX1 antibodies (SOX1-abs) are associated with paraneoplastic neurological syndromes (PNS) and small cell lung cancer (SCLC). In many clinical laboratories SOX1-abs are determined by commercial line blots without confirmation by cell-based assay (CBA) with HEK293 cells expressing SOX1. However, the diagnostic yield of commercial line blots is low and the accessibility to the CBA, that is not commercially available, limited. Here, we evaluated if the addition of the band intensity data of the line blot and the immunoreactivity in a tissue-based assay (TBA) improve the diagnostic performance of the line blot. We examined serum of 34 consecutive patients with adequate clinical information that tested positive for SOX1-abs in a commercial line blot. Samples were also assessed by TBA and CBA. SOX1-abs were confirmed by CBA in 17 (50%) patients, all (100%) had lung cancer (SCLC in 16) and 15/17 (88%) had a PNS. In the remaining 17 patients the CBA was negative and none had PNS associated with lung cancer. TBA was assessable in 30/34 patients and SOX1-abs reactivity was detected in 15/17 (88%) with positive and in 0/13 (0%) with negative CBA. Only 2 (13%) of the 15 TBA-negative patients were CBA-positive. The frequency of TBA-negative but CBA-positive increased from 10% (1/10) when the band intensity of the line blot was weak to 20% (1/5) in patients with a moderate or strong intensity band. Confirmation by CBA should be mandatory for samples (56% in this series) not assessable (4/34; 12%) or negative in the TBA (15/34; 44%).This study was funded by Instituto de Salud Carlos III - Subdirección General de Evaluación y Formento de la Investigación Sanitaria and co-funded by European Union, FIS (PI21/00255, RR-G)

Evaluating the cost-utility of a direct transfer to angiosuite protocol within 6 h of symptom onset in suspected large vessel occlusion patients

Catalonia healthcare; Cost-utility; Large vessel occlusionSanitat de Catalunya; Cost-utilitat; Oclusió de grans vasosSanidad de Cataluña; Coste-utilidad; Oclusión de grandes vasosIntroduction A direct transfer to angiosuite (DTAS) protocol has shown to be effective and safe by shortening in-hospital workflows and encouraging long-term outcome benefits. To implement DTAS at a new facility, a large organizational effort is necessary. We performed a cost-utility analysis and budget impact analysis (BIA) of the operation of a new angiosuite, primarily dedicated to stroke patients, that allows facilities to approximate the cost implications of utilizing a DTAS pathway. Methods Sixty-one patients who underwent endovascular treatment (EVT) following DTAS were matched for baseline variables to 117 patients who underwent a conventional imaging protocol at a hospital in Catalonia, Spain. An economic model, based on actual data from these patients, was developed to assess the short- and long-term clinical and economic implications of DTAS. In the BIA, the DTAS scenario was gradually implemented for 20% of patients each year until reaching a plateau at 80% of patients in the DTAS pathway. Initial investment and additional organizational costs, €4 million, were taken into consideration to compare the budget impact of the DTAS scenario with no organizational changes over five years. Results DTAS was associated with better patient functional independence rates (mRS 0–2: 50.9% vs. 41.0%) and a quality-adjusted life-years gain of 0.82 per patient. Despite the additional initial investment, DTAS development was associated with an estimated 10.2% reduction (€14.7 million) of the total costs (€144.5 million). Cost savings were mainly due to long-term associated costs related to patient disability (€13.2 million). Limitations The study relies on data obtained from a single-center, and therefore it may be difficult to generalize the findings Conclusions Our economic model predicts that the implementation of a DTAS program is cost-effective compared with no organizational changes. Our model also predicts better clinical outcomes for patients in terms of functional independence and quality-adjusted life years.This study was sponsored by Medtronic

Algorithm to improve the diagnosis of paraneoplastic neurological syndromes associated with SOX1 antibodies

SOX1 antibodies (SOX1-abs) are associated with paraneoplastic neurological syndromes (PNS) and small cell lung cancer (SCLC). In many clinical laboratories SOX1-abs are determined by commercial line blots without confirmation by cell-based assay (CBA) with HEK293 cells expressing SOX1. However, the diagnostic yield of commercial line blots is low and the accessibility to the CBA, that is not commercially available, limited. Here, we evaluated if the addition of the band intensity data of the line blot and the immunoreactivity in a tissue-based assay (TBA) improve the diagnostic performance of the line blot. We examined serum of 34 consecutive patients with adequate clinical information that tested positive for SOX1-abs in a commercial line blot. Samples were also assessed by TBA and CBA. SOX1-abs were confirmed by CBA in 17 (50%) patients, all (100%) had lung cancer (SCLC in 16) and 15/17 (88%) had a PNS. In the remaining 17 patients the CBA was negative and none had PNS associated with lung cancer. TBA was assessable in 30/34 patients and SOX1-abs reactivity was detected in 15/17 (88%) with positive and in 0/13 (0%) with negative CBA. Only 2 (13%) of the 15 TBA-negative patients were CBA-positive. The frequency of TBA-negative but CBA-positive increased from 10% (1/10) when the band intensity of the line blot was weak to 20% (1/5) in patients with a moderate or strong intensity band. Confirmation by CBA should be mandatory for samples (56% in this series) not assessable (4/34; 12%) or negative in the TBA (15/34; 44%)

Headache : A striking prodromal and persistent symptom, predictive of COVID-19 clinical evolution

To define headache characteristics and evolution in relation to COVID-19 and its inflammatory response. This is a prospective study, comparing clinical data and inflammatory biomarkers of COVID-19 patients with and without headache, recruited at the Emergency Room. We compared baseline with 6-week follow-up to evaluate disease evolution. Of 130 patients, 74.6% (97/130) had headache. In all, 24.7% (24/97) of patients had severe pain with migraine-like features. Patients with headache had more anosmia/ageusia (54.6% vs. 18.2%; p < 0.0001). Clinical duration of COVID-19 was shorter in the headache group (23.9 ± 11.6 vs. 31.2 ± 12.0 days; p = 0.028). In the headache group, IL-6 levels were lower at the ER (22.9 (57.5) vs. 57.0 (78.6) pg/mL; p = 0.036) and more stable during hospitalisation. After 6 weeks, of 74 followed-up patients with headache, 37.8% (28/74) had ongoing headache. Of these, 50% (14/28) had no previous headache history. Headache was the prodromal symptom of COVID-19 in 21.4% (6/28) of patients with persistent headache (p = 0.010). Headache associated with COVID-19 is a frequent symptom, predictive of a shorter COVID-19 clinical course. Disabling headache can persist after COVID-19 resolution. Pathophysiologically, its migraine-like features may reflect an activation of the trigeminovascular system by inflammation or direct involvement of SARS-CoV-2, a hypothesis supported by concomitant anosmia

How Do Cancer-Related Mutations Affect the Oligomerisation State of the p53 Tetramerisation Domain?

Tumour suppressor p53 plays a key role in the development of cancer and has therefore been widely studied in recent decades. While it is well known that p53 is biologically active as a tetramer, the tetramerisation mechanism is still not completely understood. p53 is mutated in nearly 50% of cancers, and mutations can alter the oligomeric state of the protein, having an impact on the biological function of the protein and on cell fate decisions. Here, we describe the effects of a number of representative cancer-related mutations on tetramerisation domain (TD) oligomerisation defining a peptide length that permits having a folded and structured domain, thus avoiding the effect of the flanking regions and the net charges at the N- and C-terminus. These peptides have been studied under different experimental conditions. We have applied a variety of techniques, including circular dichroism (CD), native mass spectrometry (MS) and high-field solution NMR. Native MS allows us to detect the native state of complexes maintaining the peptide complexes intact in the gas phase; the secondary and quaternary structures were analysed in solution by NMR, and the oligomeric forms were assigned by diffusion NMR experiments. A significant destabilising effect and a variable monomer population were observed for all the mutants studied

Development of simple and transferable molecular models for biodiesel production with the soft-SAFT equation of state

The knowledge of fatty acid esters/biodiesels thermodynamic properties is crucial not only for developing optimal biodiesel production and purification processes, but also for enhancing biodiesels performance in engines. This work is intended to apply a simple but reliable theoretically based sound model, the soft-SAFT EoS, as a tool for the development, design, scale-up, and optimization of biodiesels production and purification processes. A molecular model within the soft-SAFT EoS framework is proposed for the fatty acid esters, and the Density Gradient Theory approach is coupled into soft-SAFT for the description of interfacial properties, while the Free-Volume Theory is used for the calculation of viscosities, in an integrated model. For pressures up to 150 MPa, and in the temperature range 288.15-423.15K, density, surface tension, viscosity and speed of sound data for fatty acid methyl and ethyl esters, ranging from C-8:0 to C-24:0, with up to three unsaturated bonds, are described with deviations inferior to 5%. Finally, in order to validate the predictive ability of the model to be applied in the biodiesel groundwork, the high pressure densities and viscosities for 8 biodiesels were predicted with the soft-SAFT EoS, reinforcing the validity of the approach to obtain reliable predictions for engineering purposes. (C) 2014 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved