Both quality of life (QoL) and comorbidity influence therapy and prognosis of non-small-cell lung cancer (NSCLC). We previously developed a lung cancer disease-specific simplified comorbidity score ...(SCS) and demonstrated the prognostic impact of this disease-specific instrument. This study aimed at validating the SCS in a prospective bicentric NSCLC population by measuring its relative prognostic determinant impact taking into account well-established variables such as QoL, performance status (PS), Charlson comorbidity index (CCI) and disease stage.
Prognostic values of different pretherapeutic features were tested in univariate and multivariate analyses in a population of 301 NSCLC.
Median survival was 17 months. One-third of patients reporting difficulties in their normal daily activities and an overall poor QoL. The following pretreament variables were independent determinants of a shorter overall survival: advanced disease, SCS, Lung Cancer Symptoms Scale global symptoms score, anaemia, hyponatremia, serum alkaline phosphatases level, serum CYFRA 21-1 and serum neuron-specific enolase.
In this extended validation population, the SCS is more informative than the CCI in predicting NSCLC patient outcome as the former is also more disease specific. Combination of both SCS comorbidity score and LSCC QoL yields a more accurate information that conventional analysis of PS.
Er3+-doped and Er3+-Yb3+ co-doped GdVO4 crystals with different Er3+ and Yb3+ concentrations have been synthesized by the high temperature solid-state reaction method. The X-ray powder diffraction ...patterns indicated that the obtained materials were pure tetragonal phase. The different performance of these luminescent thermometers in terms of thermal sensitivities and temperature uncertainties when operated under conditions of down or up-conversion were studied, in the non-saturation regime, using the self-referenced fluorescence intensity ratio technique. The calculated absolute and relative sensitivities and temperature uncertainties, in the 300–453 K temperature range can be found in the range 7.16–12.56 10−3 K−1, 0.83–1.34% K−1 and 0.37–0.60 K, respectively, with the low temperature bound determined to be 110–150 K. This work confirmed that a thermal effect generated by the excitation light can be ignored in the down-conversion luminescence process, while it has some implications in the upconversion luminecence mechanism. Therefore, the down-conversion emission gives rise to the highest thermal sensitivities and the best thermal resolution in comparison with the up-conversion emission, with values of 1.34% K−1 and 0.37 K at 300 K, respectively, in 2 at.% Er, 8 at.% Yb: GdVO4 MCs. These results reveal that it is preferable to operate these materials for luminescence temperature sensors under a down-conversion process to achieve the best performance.
•Er3+: GdVO4 and Er3+/ Yb3+: GdVO4 luminescent microparticles can be used as luminescent thermometers in the 110-450 K temperature range with 0.83-1.34 % K-1 as relative thermal sensitivities.•Best thermometric performance can be achieved under the down-conversion process in comparison with the up-conversion process in Er3+: GdVO4 and Er3+/ Yb3+:GdVO4 luminescent microparticles.
Treatment of non-small-cell lung cancer (NSCLC) might take into account comorbidities as an important variable. The aim of this study was to generate a new simplified comorbidity score (SCS) and to ...determine whether or not it improves the possibility of predicting prognosis of NSCLC patients. A two-step methodology was used. Step 1: An SCS was developed and its prognostic value was compared with classical prognostic determinants in the outcome of 735 previously untreated NSCLC patients. Step 2: the SCS reliability as a prognostic determinant was tested in a different population of 136 prospectively accrued NSCLC patients with a formal comparison between SCS and the classical Charlson comorbidity index (CCI). Prognosis was analysed using both univariate and multivariate (Cox model) statistics. The SCS summarised the following variables: tobacco consumption, diabetes mellitus and renal insufficiency (respective weightings 7, 5 and 4), respiratory, neoplastic and cardiovascular comorbidities and alcoholism (weighting=1 for each item). In step 1, aside from classical variables such as age, stage of the disease and performance status, SCS was a statistically significant prognostic variable in univariate analyses. In the Cox model weight loss, stage grouping, performance status and SCS were independent determinants of a poor outcome. There was a trend towards statistical significance for age (P=0.08) and leucocytes count (P=0.06). In Step 2, both SCS and well-known prognostic variables were found as significant determinants in univariate analyses. There was a trend towards a negative prognostic effect for CCI. In multivariate analysis, stage grouping, performance status, histology, leucocytes, lymphocytes, lactate dehydrogenase, CYFRA 21-1 and SCS were independent determinants of a poor prognosis. CCI was removed from the Cox model. In conclusion, the SCS, constructed as an independent prognostic factor in a large NSCLC patient population, is validated in another prospective population and appears more informative than the CCI in predicting NSCLC patient outcome.
Highlights • The incidence and trends of it of the different subtypes of Non Melanoma Skin Cancers are analyzed. • Observed and relative survival at 3, 5 and 10 years of Non Melanoma Skin Cancers are ...shown. • The comparison of epidemiological topics between countries is discussed.
Type 1 diabetes (T1D) is caused by the selective destruction of the insulin-producing β cells of the pancreas by an autoimmune response. Due to ethical and practical difficulties, the features of the ...destructive process are known from a small number of observations, and transcriptomic data are remarkably missing. Here we report whole genome transcript analysis validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and correlated with immunohistological observations for four T1D pancreases (collected 5 days, 9 months, 8 and 10 years after diagnosis) and for purified islets from two of them. Collectively, the expression profile of immune response and inflammatory genes confirmed the current views on the immunopathogenesis of diabetes and showed similarities with other autoimmune diseases; for example, an interferon signature was detected. The data also supported the concept that the autoimmune process is maintained and balanced partially by regeneration and regulatory pathway activation, e.g. non-classical class I human leucocyte antigen and leucocyte immunoglobulin-like receptor, subfamily B1 (LILRB1). Changes in gene expression in islets were confined mainly to endocrine and neural genes, some of which are T1D autoantigens. By contrast, these islets showed only a few overexpressed immune system genes, among which bioinformatic analysis pointed to chemokine (C-C motif) receptor 5 (CCR5) and chemokine (CXC motif) receptor 4) (CXCR4) chemokine pathway activation. Remarkably, the expression of genes of innate immunity, complement, chemokines, immunoglobulin and regeneration genes was maintained or even increased in the long-standing cases. Transcriptomic data favour the view that T1D is caused by a chronic inflammatory process with a strong participation of innate immunity that progresses in spite of the regulatory and regenerative mechanisms.
Purpose
Pseudoxanthoma elasticum (PXE) is a recessive disorder involving skin, eyes and arteries, mainly caused by ABCC6 pathogenic variants. However, almost one fifth of patients remain genetically ...unsolved despite extensive genetic screening of ABCC6, as illustrated in a large French PXE series of 220 cases. We searched for new PXE gene(s) to solve the ABCC6‐negative patients.
Methods
First, family‐based exome sequencing was performed, in one ABCC6‐negative PXE patient with additional neurological features, and her relatives. CYP2U1, involved in hereditary spastic paraplegia type 56 (SPG56), was selected based on this complex phenotype, and the presence of two candidate variants. Second, CYP2U1 sequencing was performed in a retrospective series of 46 additional ABCC6‐negative PXE probands. Third, six additional SPG56 patients were evaluated for PXE skin and eye phenotype. Additionally, plasma pyrophosphate dosage and functional analyses were performed in some of these patients.
Results
6.4% of ABCC6‐negative PXE patients (n = 3) harboured biallelic pathogenic variants in CYP2U1. PXE skin lesions with histological confirmation, eye lesions including maculopathy or angioid streaks, and various neurological symptoms were present. CYP2U1 missense variants were confirmed to impair protein function. Plasma pyrophosphate levels were normal. Two SPG56 patients (33%) presented some phenotypic overlap with PXE.
Conclusion
CYP2U1 pathogenic variants are found in unsolved PXE patients with neurological findings, including spastic paraplegia, expanding the SPG56 phenotype and highlighting its overlap with PXE. The pathophysiology of ABCC6 and CYP2U1 should be explored to explain their respective role and potential interaction in ectopic mineralization.
Background Sensory phenomena (SP) are uncomfortable feelings, including bodily sensations, sense of inner tension, “just-right” perceptions, feelings of incompleteness, or “urge-only” phenomena, ...which have been described to precede, trigger or accompany repetitive behaviours in individuals with obsessive–compulsive disorder (OCD). Sensory phenomena are also observed in individuals with tic disorders, and previous research suggests that sensorimotor cortex abnormalities underpin the presence of SP in such patients. However, to our knowledge, no studies have assessed the neural correlates of SP in patients with OCD. Methods We assessed the presence of SP using the University of São Paulo Sensory Phenomena Scale in patients with OCD and healthy controls from specialized units in São Paulo, Brazil, and Barcelona, Spain. All participants underwent a structural magnetic resonance examination, and brain images were examined using DARTEL voxel-based morphometry. We evaluated grey matter volume differences between patients with and without SP and healthy controls within the sensorimotor and premotor cortices. Results We included 106 patients with OCD and 87 controls in our study. Patients with SP (67% of the sample) showed grey matter volume increases in the left sensorimotor cortex in comparison to patients without SP and bilateral sensorimotor cortex grey matter volume increases in comparison to controls. No differences were observed between patients without SP and controls. Limitations Most patients were medicated. Participant recruitment and image acquisition were performed in 2 different centres. Conclusion We have identified a structural correlate of SP in patients with OCD involving grey matter volume increases within the sensorimotor cortex; this finding is in agreement with those of tic disorder studies showing that abnormal activity and volume increases within this region are associated with the urges preceding tic onset.
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