Predicting response to radiotherapy of head and neck squamous cell carcinoma using radiomics from cone-beam CT images.

INTRODUCTION: Radiotherapy (RT) for head and neck cancer is now guided by cone-beam computed tomography (CBCT). We aim to identify a CBCT radiomic signature predictive of progression to RT. MATERIAL AND METHODS: A cohort of 93 patients was split into training (n = 60) and testing (n = 33) sets. A total of 88 features were extracted from the gross tumor volume (GTV) on each CBCT. Receiver operating characteristic (ROC) curves were used to determine the power of each feature at each week of treatment to predict progression to radio(chemo)therapy. Only features with AUC > 0.65 at each week were pre-selected. Absolute differences were calculated between features from each weekly CBCT and baseline CBCT1 images. The smallest detectable change (C = 1.96 × SD, SD being the standard deviation of differences between feature values calculated on CBCT1 and CBCTn) with its confidence interval (95% confidence interval [CI]) was determined for each feature. The features for which the change was larger than C for at least 5% of patients were then selected. A radiomics-based model was built at the time-point that showed the highest AUC and compared with models relying on clinical variables. RESULTS: Seven features had an AUC > 0.65 at each week, and six exhibited a change larger than the predefined CI 95%. After exclusion of inter-correlated features, only one parameter remains, Coarseness. Among clinical variable, only hemoglobin value was significant. AUC for predicting the treatment response were 0.78 (p = .006), 0.85 (p < .001), and 0.99 (p < .001) for clinical, CBCT4-radiomics (Coarseness) and clinical + radiomics based models respectively. The mean AUC of this last model on a 5-fold cross-validation was 0.80 (±0.09). On the testing cohort, the best prediction was given by the combined model (balanced accuracy [BAcc] 0.67 , p < .001). CONCLUSIONS: We described a feature selection methodology for delta-radiomics that is able to select reproducible features which are informative due to their change during treatment. A selected delta radiomics feature may improve clinical-based prediction models.

Rapid diagnostic tests for infectious diseases in the emergency department.

BACKGROUND: Rapid diagnostic tests (RDTs) for infectious diseases, with a turnaround time of less than 2 hours, are promising tools that could improve patient care, antimicrobial stewardship and infection prevention in the emergency department (ED) setting. Numerous RDTs have been developed, although not necessarily for the ED environment. Their successful implementation in the ED relies on their performance and impact on patient management. OBJECTIVES: The aim of this narrative review was to provide an overview of currently available RDTs for infectious diseases in the ED. SOURCES: PubMed was searched through August 2019 for available studies on RDTs for infectious diseases. Inclusion criteria included: commercial tests approved by the US Food and Drug Administration (FDA) or Conformité Européenne (CE) in vitro diagnostic devices with data on clinical samples, ability to run on fully automated systems and result delivery within 2 hours. CONTENT: A nonexhaustive list of representative commercially available FDA- or CE-approved assays was categorized by clinical syndrome: pharyngitis and upper respiratory tract infection, lower respiratory tract infection, gastrointestinal infection, meningitis and encephalitis, fever in returning travellers and sexually transmitted infection, including HIV. The performance of tests was described on the basis of clinical validation studies. Further, their impact on clinical outcomes and anti-infective use was discussed with a focus on ED-based studies. IMPLICATIONS: Clinicians should be familiar with the distinctive features of each RDT and individual performance characteristics for each target. Their integration into ED work flow should be preplanned considering local constraints of given settings. Additional clinical studies are needed to further evaluate their clinical effectiveness and cost-effectiveness.

Vitamin D3 a new drug against Candida albicans.

OBJECTIVE: In this study, we demonstrate that vitamin D3 had fungicidal activity against Candida albicans. MATERIAL AND METHODS: The susceptibility of the yeast strain to the vitamin D3 was investigated by the antimicrobial screening using modified agar diffusion method, minimum fungistatic concentrations (MFCs) and minimum fungicide concentrations (MFCC) of the vitamin D3 were determined by the broth dilution method. RESULTS: The antifungal activity indicted that 100µg/ml of vitamin D3 had a power inhibition in the growth of C. albicans with zone of inhibition 12.5mm and CMFC and CMFs were 1.58±0.0764µg/ml. CONCLUSION: These values indicate that vitamin D3 can be considered to have fungicide activity. This antifungal effect may be due to the large lipsolubility of vitamin D3 changing the integrity of the cell membrane.

CREM variant rs17583959 conferred susceptibility to T1D risk in the Tunisian families.

Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease caused by the destruction of insulin-producing pancreatic ß-cells by autoreactive T cells. Studies in animal models, such as the non-obese diabetic (NOD) mouse reveal that this disease is under the control of several genes that encode molecules implicated in regulation of transcription factors and in T cell activation. In order to underline the role of the genes involved in this regulation pathways, we investigated, using the Sequenom MassARRAY platform, 13 single-nucleotide polymorphisms (SNPs) belonging to CREM, IRF5, STAT4, and STAT5a/b genes in 59 T1D Tunisian families. In the current study, we identified an association with rs17583959 (allele G; Z score=2.27; p=0.02; Genotype GG: score=1.96; p=0.04) of CREM gene. In LD analysis a strong LD between the 3 CREM variants (Block 1) was detected; rs2384352 was in complete LD with rs1148247. When haplotypes were constructed between CREM polymorphisms (rs1148247, rs17583959, rs2384352), AGA haplotype (H2) was significantly over-transmitted from parents to affected offspring (Z score=2.988; P=0.002) and may confer a risk for T1D disease. Whereas, AAG haplotype (H5) (Z score=-2.000; p=0.045) was less transmitted than expected to affected children suggesting its protective effect against T1D pathology. No significant association in IRF5, STAT4, and STAT5a/b genes were observed. In conclusion, this study shows an eventually involvement of CREM gene in the development of T1D pathology in Tunisian families. These facts are consistent with a major role for transcription factor genes involved in the immune pathways in the control of autoimmunity. Further researches of association and functional analysis across populations are needed to confirm these findings.

Association of TCR/CD3, PTPN22, CD28 and ZAP70 gene polymorphisms with type 1 diabetes risk in Tunisian population: family based association study.

Type 1 diabetes (T1D) is caused by an immune-mediated destruction of the insulin-producing ß-cells. Several studies support the involvement of T cell activation molecules in the pathogenesis of T1D. In order to underline the role of the genes involved in this activation pathway, we investigated, using the Sequenom MassARRAY platform, 45 single-nucleotide polymorphisms (SNPs) belonging to TCR/CD3, CD28, ZAP70, and PTPN22 genes in 59 T1D Tunisian families. In the current study, we identified an association with rs706 (Z score=2.782; p=0.005) of TCRß gene. We also demonstrated that rs10918706 in the intron of the CD3z gene was associated with increased risk of T1D (Z score 2.137; p=0.032). In the same region, rs2949655 (Z score=2.101; p=0.035) and rs1214611 (Z score=4.036; p=0.00005) showed a genotype association with the risk of T1D. When haplotypes were constructed, GAA haplotype displayed significant association with T1D (Z score=2.135; p=0.032), while GGA haplotype (Z score=-1.988; p=0.046) was negatively associated with the disease. We also identified an association with rs3181096 (Z score=2.177; p=0.029), rs17695937 (Z score =2.111; p=0.034) and rs2488457 (Z score=2.219; p=0.026), respectively of CD28, ZAP70 and PTPN22 genes. In addition, our results suggest a significant effect on T1D susceptibility for AC (Z score=2.30; p=0.02) and CTGGC (Z score=2.309, p=0.02) haplotypes of ZAP70 and PTPN22 genes, respectively. While, the GTCT (Z score=-2.114, p=0.034) and CTAGG (Z score=-2.121, p=0.033) haplotypes of CD28 and PTPN22 genes, may confer protection against T1D. These findings confirm the role of PTPN22 and CD28 involved in the T cell activation pathway in the development of T1D in Tunisian families. Interestingly, ZAP70 and TCRß/CD3z seem to contribute to the susceptibility to the disease in our population. However, this finding has to be confirmed in further studies.

Association of the RAVER2 gene with increased susceptibility for ulcerative colitis.

Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE) and autoimmune polyglandular syndromes (APS) are autoimmune diseases (ADs) that may share common susceptibility pathways. We examined ribonucleo-protein, polypyrimidine tract-binding protein (PTB)-binding 2 (RAVER2) loci for these diseases in a cohort of 39 CD cases, 67 UC cases, 93 SLE cases, 60 APS cases and 162 healthy control subjects of Tunisian origin. We genotyped 3 SNPs of RAVER2 (rs2780814, rs1333739 and rs2780889) and evaluated it genetic association with each ADs, using X2-test. For each association, odds ratio (OR) and 95% CI were calculated. We show that rs2780814 is significantly associated with UC (P = 0.00016, P(corr) = 0.00048, OR = 3.66 (1.82; 7.34)). We also observed a trend of possible association to SLE (P = 0.023, P(corr) = 0.69, OR = 2.19 (1.1; 4.36)). None of these RAVER2 SNPs were associated with CD and APS susceptibility. These findings establish RAVER2 as a new UC genetic susceptibility factor and reveal a genetic heterogeneity of the associated polymorphisms and risk alleles between ADs suggesting different immunopathological roles of RAVER2 in these diseases.

[Dosimetric comparison between the intensity modulated radiotherapy with fixed field and Rapid Arc of cervix cancer]. / Comparaison dosimétrique des radiothérapies conformationnelles avec modulation d'intensité par faisceaux statiques et RapidArc(®) des cancers du col.

PURPOSE: Concurrent radiochemotherapy is the standard treatment for locally advanced cervical cancer. This treatment is responsible for bowel and hematologic toxicities. The use of intensity-modulated radiotherapy (IMRT), in static beams, allows a decrease of this toxicity. The technique of RapidArc(®) IMRT could lower the dose delivered to the organs at risk and improve the homogeneity of the planning target volume coverage, while decreasing the processing time. PATIENTS AND MATERIALS: For 20 patients, treatment plans performed with IMRT and RapidArc(®) were compared. The target volumes were: the clinical target volume (gross tumour volume, uterus, upper third of the vagina, the hypogastric, iliac and presacral nodal regions), and the planning target volume (clinical target volume+1cm). The delineated organs at risk were: rectum, bladder, bowel and bone marrow. The dose was 45 Gy in 25 fractions. IMRT were delivered with five beams and RapidArc(®) with two arcs. The comparisons were made by the non-parametric test of Wilcoxon. RESULTS: Medium coverage of the planning target volume was better with RapidArc(®) (P=0.01). It was also better regarding the sparing of bowel (P=0.01) and IMRT was better regarding the sparing of bladder (P=0.01) and rectum (P=0.05). The total volume receiving 20 Gy was less important with RapidArc(®) (P<0.001). RapidArc(®) allowed to decrease the treatment time (3 versus 12 minutes with IMRT) and the number of monitor units (MU) (376.5 versus 962.2, on average, P=0.0001). CONCLUSION: The technique of RapidArc(®) seems to obtain better dosimetric results compared to RCMI, with fewer MU, and a significant decrease in treatment time.

Dietary magnesium intake in a French adult population.

Magnesium intake was assessed using six 24-h dietary records during a 1-year period in 5,448 subjects (3,111 women 35-60 yrs old and 2,337 men 45-60 yrs old) in the SU.VI.MAX cohort, selected at a national level in France. The overall mean dietary intake was estimated at 369 +/- 106 mg/day in men and 280 +/- 84 mg/day in women. 77 per cent of women and 72 per cent of men had dietary magnesium intakes lower than recommended dietary allowances; 23 per cent of women and 18 per cent of men consumed less than 2/3 of these RDA. A strong positive correlation existed between energy and magnesium intake (r = 0.79; p < 10(-4)). Slight variations were observed according to socio-professional and educational levels and place of residence. Cereal products represented the main contribution in both men (21 per cent) and women (19.8 per cent). In men, the second source was represented by alcoholic beverages (11.7 per cent), which were a lower source of magnesium in women (5.5 per cent). Dairy products, vegetables, meat and poultry were the other main sources of dietary magnesium intake.