BACKGROUND: The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients. PATIENTS AND METHODS: We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA-IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group. RESULTS: The risks of recurrence (hazard ratio [HR] 1.154, 95% confidence intervals [CI] 0.799-1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458-1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690-1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort. CONCLUSION: We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation. CLINICAL TRIALS IDENTIFIER: NCT04037124.
- MeSH
- analýza přežití MeSH
- dospělí MeSH
- hysterektomie metody MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory děložního čípku mortalita patologie chirurgie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel (T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated. Depending on the database-guided results, patients were categorized as: (i) typical T, B or Myeloid without or; (ii) with a transitional component to another lineage; (iii) atypical; or (iv) mixed-lineage. Using this automated algorithm, in 781/783 cases (99.7%) the right panel was selected, and data comparable to the final WHO-diagnosis was already provided in >93% of cases (85% T-ALL, 97% BCP-ALL, 95% AML and 87% mixed-phenotype AL patients), even without data on the full-characterization panels. Our results show that database-guided analysis facilitates standardized interpretation of ALOT results and allows accurate selection of the relevant classification panels, hence providing a solid basis for designing future WHO AL classifications.
- MeSH
- akutní lymfatická leukemie patologie MeSH
- akutní myeloidní leukemie patologie MeSH
- akutní nemoc MeSH
- dítě MeSH
- dospělí MeSH
- imunofenotypizace metody MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Susceptibility to environmental stressors has been described for fetal and early childhood development. However, the possible susceptibility of the prepubertal period, characterized by the orchestration of the organism towards sexual maturation and adulthood has been poorly investigated and exposure data are scarce. In the current study levels of cadmium (Cd), cotinine and creatinine in urine were analyzed in a subsample 216 children from 12 European countries within the DEMOCOPHES project. The children were divided into six age-sex groups: boys (6-8 years, 9-10 years and 11 years old), and girls (6-7 years, 8-9 years, 10-11 years). The number of subjects per group was between 23 and 53. The cut off values were set at 0.1 µg/L for Cd, and 0.8 µg/L for cotinine defined according to the highest limit of quantification. The levels of Cd and cotinine were adjusted for creatinine level. In the total subsample group, the median level of Cd was 0.180 µg/L (range 0.10-0.69 µg/L), and for cotinine the median wet weight value was 1.50 µg/L (range 0.80-39.91 µg/L). There was no significant difference in creatinine and cotinine levels between genders and age groups. There was a significant correlation between levels of cadmium and creatinine in all children of both genders. This shows that even at such low levels the possible effect of cadmium on kidney function was present and measurable. An increase in Cd levels was evident with age. Cadmium levels were significantly different between 6-7 year old girls, 11 year old boys and 10-11 year old girls. As there was a balanced distribution in the number of subjects from countries included in the study, bias due to data clustering was not probable. The impact of low Cd levels on kidney function and gender differences in Cd levels needs further investigation.
- MeSH
- biologické markery moč MeSH
- dítě MeSH
- kadmium moč MeSH
- kotinin moč MeSH
- kreatinin moč MeSH
- lidé MeSH
- monitorování životního prostředí metody MeSH
- pohlavní dimorfismus * MeSH
- puberta moč MeSH
- stárnutí moč MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
Several quantitative trait loci (QTL) for different meat quality traits have been localized on the q arm of porcine chromosome 2 at position 55-78 cM. Association analyses were performed in a commercial Landrace × Chinese-European (LCE) crossbred population (n = 446) slaughtered at approximately 127 kg and an average age of 198 days with records for performance (growth, fat and meat accretion) and meat quality [intramuscular fat (IMF), Minolta L*, Minolta a*, Minolta b* and pH at 45 m]. Polymorphisms within positional candidate genes cloned from homologous regions on human chromosome 19, ubiquitin-like 5 (UBL5- AM950288:g.566G>A), resistin (RETN- AM157180:g.1473A>G causing substitution p.Ala36Thr), insulin receptor (INSR- AM950289:g.589T>C) and complement factor D (adipsin) (CFD- AM950287:g. 306C>T) were located at positions 62.1, 64.0, 68.0 and 70.7 cM respectively on the current USDA USMARC map of porcine chromosome 2 and had the following allele frequencies in the LCE: UBL5 566G - 0.57; RETN 1473G - 0.84; INSR 589C - 0.70; and CFD 306C - 0.73. The effects of alleles within the candidate genes on the recorded traits were estimated using an animal model. Significant effects (P < 0.05) were found for pH(45) in m. semimembranosus (m. sm.) (UBL5), IMF (RETN) and Minolta L* (RETN, CFD). Differences between phenotypic means of homozygotes at UBL5, RETN and either RETN or CFD explained 0.34 SD for pH(45) in m. sm., 0.47 SD for IMF and 0.68 SD for Minolta L* respectively. Suggestive effects (P < 0.10) on IMF (UBL5, CFD), Minolta a* (INSR, CFD) and Minolta b* (INSR) were also observed. Our results support the localization of further QTL for meat quality traits in this region and suggest that there are several genes affecting different meat quality traits.
- MeSH
- fenotyp MeSH
- frekvence genu MeSH
- genetické asociační studie MeSH
- glukosa metabolismus MeSH
- jednonukleotidový polymorfismus MeSH
- klonování DNA MeSH
- lokus kvantitativního znaku MeSH
- mapování chromozomů MeSH
- maso normy MeSH
- polymerázová řetězová reakce MeSH
- Sus scrofa genetika růst a vývoj MeSH
- tuky metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
NAMPT encodes an enzyme catalysing the rate-limiting step in NAD biosynthesis. The extracellular form of the enzyme is known as adipokine visfatin. We detected SNP AM999341:g.669T>C (referred to as 669T>C) in intron 9 and SNP FN392209:g.358A>G (referred to as 358A>G) in the promoter of the gene. RH mapping linked the gene to microsatellite SW944. Linkage analysis placed the gene on the current USDA – USMARC linkage map at position 92 cM on SSC9. Association analyses were performed in a wild boar × Meishan F2 family (W × M), with 45 traits recorded (growth and fattening, fat deposition, muscling, meat quality, stress resistance and other traits), and in a commercial Landrace × Chinese-European (LCE) synthetic population with records for 15 traits (growth, fat deposition, muscling, intramuscular fat, meat colour and backfat fatty acid content). In the W × M, SNP 669T>C was associated with muscling, fat deposition, growth and fattening, meat quality and other traits and in the LCE with muscling, meat quality and backfat fatty acid composition. In the W × M, SNP 358A>G was associated with muscling, fat deposition, growth and other traits. After correction for multiple testing, the NAMPT haplotypes were associated in the W × M with, in descending order, muscling (q = 0.0056), growth (q = 0.0056), fat deposition (q = 0.0109), fat-to-meat ratio (q = 0.0135), cooling losses (q = 0.0568) and longissimus pHU (q = 0.0695). The SNPs are hypothesized to be in linkage disequilibrium with a causative mutation affecting energy metabolism as a whole rather than fat metabolism alone.
- MeSH
- distribuce tělesného tuku MeSH
- energetický metabolismus MeSH
- genetické asociační studie metody MeSH
- haplotypy genetika MeSH
- introny genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- mapování chromozomů MeSH
- maso normy MeSH
- mikrosatelitní repetice MeSH
- nikotinamidfosforibosyltransferasa genetika MeSH
- promotorové oblasti (genetika) MeSH
- Sus scrofa genetika růst a vývoj MeSH
- vazebná nerovnováha genetika MeSH
- vývoj svalů MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- dítě MeSH
- dospělí MeSH
- kouření mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- nádory plic mortalita MeSH
- poruchy vyvolané užíváním tabáku mortalita MeSH
- senioři MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Geografické názvy
- východní Evropa MeSH