Ribonucleotide reductase subunits M1 and M2 mRNA expression levels and clinical outcome of lung adenocarcinoma patients treated with docetaxel/gemcitabine

Ribonucleotide reductase subunits M1 (RRM1) and M2 (RRM2) are involved in the metabolism of gemcitabine (2′,2′-difluorodeoxycytidine), which is used for the treatment of nonsmall cell lung cancer. The mRNA expression of RRM1 and RRM2 in tumours from lung adenocarcinoma patients treated with docetaxel/gemcitabine was assessed and the results correlated with clinical outcome. RMM1 and RMM2 mRNA levels were determined by quantitative real-time PCR in primary tumours of previously untreated patients with advanced lung adenocarcinoma who were subsequently treated with docetaxel/gemcitabine. Amplification was successful in 42 (79%) of 53 enrolled patients. Low levels of RRM2 mRNA were associated with response to treatment (P< 0.001). Patients with the lowest expression levels of RRM1 had a significantly longer time to progression (P=0.044) and overall survival (P=0.02) than patients with the highest levels. Patients with low levels of both RRM1 and RRM2 had a significantly higher response rate (60 vs 14.2%; P=0.049), time to progression (9.9 vs 2.3 months; P=0.003) and overall survival (15.4 vs 3.6; P=0.031) than patients with high levels of both RRM1 and RRM2. Ribonucleotide reductase subunit M1 and RRM2 mRNA expression in lung adenocarcinoma tumours is associated with clinical outcome to docetaxel/gemcitabine. Prospective studies are warranted to evaluate the role of these markers in tailoring chemotherapy

Immaturity of the Oculomotor Saccade and Vergence Interaction in Dyslexic Children: Evidence from a Reading and Visual Search Study

Studies comparing binocular eye movements during reading and visual search in dyslexic children are, at our knowledge, inexistent. In the present study we examined ocular motor characteristics in dyslexic children versus two groups of non dyslexic children with chronological/reading age-matched. Binocular eye movements were recorded by an infrared system (mobileEBT®, e(ye)BRAIN) in twelve dyslexic children (mean age 11 years old) and a group of chronological age-matched (N = 9) and reading age-matched (N = 10) non dyslexic children. Two visual tasks were used: text reading and visual search. Independently of the task, the ocular motor behavior in dyslexic children is similar to those reported in reading age-matched non dyslexic children: many and longer fixations as well as poor quality of binocular coordination during and after the saccades. In contrast, chronological age-matched non dyslexic children showed a small number of fixations and short duration of fixations in reading task with respect to visual search task; furthermore their saccades were well yoked in both tasks. The atypical eye movement's patterns observed in dyslexic children suggest a deficiency in the visual attentional processing as well as an immaturity of the ocular motor saccade and vergence systems interaction

Extremely Preterm Infant Admissions Within the SafeBoosC-III Consortium During the COVID-19 Lockdown

Objective: To evaluate if the number of admitted extremely preterm (EP) infants (born before 28 weeks of gestational age) differed in the neonatal intensive care units (NICUs) of the SafeBoosC-III consortium during the global lockdown when compared to the corresponding time period in 2019. Design: This is a retrospective, observational study. Forty-six out of 79 NICUs (58%) from 17 countries participated. Principal investigators were asked to report the following information: (1) Total number of EP infant admissions to their NICU in the 3 months where the lockdown restrictions were most rigorous during the first phase of the COVID-19 pandemic, (2) Similar EP infant admissions in the corresponding 3 months of 2019, (3) the level of local restrictions during the lockdown period, and (4) the local impact of the COVID-19 lockdown on the everyday life of a pregnant woman. Results: The number of EP infant admissions during the first wave of the COVID-19 pandemic was 428 compared to 457 in the corresponding 3 months in 2019 (−6.6%, 95% CI −18.2 to +7.1%, p = 0.33). There were no statistically significant differences within individual geographic regions and no significant association between the level of lockdown restrictions and difference in the number of EP infant admissions. A post-hoc analysis based on data from the 46 NICUs found a decrease of 10.3%in the total number of NICU admissions (n = 7,499 in 2020 vs. n = 8,362 in 2019). Conclusion: This ad hoc study did not confirm previous reports of a major reduction in the number of extremely pretermbirths during the first phase of the COVID-19 pandemic. Clinical Trial Registration: ClinicalTrial.gov, identifier: NCT04527601 (registered August 26, 2020), https://clinicaltrials.gov/ct2/show/NCT04527601

P4-07-21: A Comparison of Two Methods for the Detection of Circulating Tumor Cells (CTCs) in Patients (pts) with Early and Metastatic Breast Cancer (BC): RT-PCR for Cytokeratin (CK) −19 mRNA Versus the CellSearch System.

Abstract Background: Different methods are available for the detection of CTCs in pts with BC, however, the variable performance of these assays, the heterogeneity of CTCs, and the possible treatment-induced alteration of the markers evaluated, imply that no ideal method currently exists. We compared the efficiency of two methods to detect CTCs in pts with BC. Patients and Methods: Blood was obtained from 200 pts with early and 164 with metastatic BC before the start of adjuvant or first-line chemotherapy, respectively. Different aliquots of the same sample were evaluated by RT-PCR for CK-19 mRNA and by the CellSearch System. Blood samples were available after the end of adjuvant or first-line therapy in 99 and 93 pts, respectively. CTCs in 23 and 7.5 ml of blood were enumerated by CellSearch, in adjuvant and metastatic pts, respectively. Cut-off values of ≥1 and ≥2 CTCs/23 ml and ≥2 and ≥5 CTCs/7.5 ml were used. Twenty ml of blood were obtained for mRNA extraction in all RT-PCR experiments. Results: In early BC, 18.0% of samples were positive prior to therapy by RT-PCR and 37.0% (CTC≥1) and 16.5% (CTC≥2) by CellSearch. No significant correlation was shown for the detection of CTCs between methods. Overall (positive and negative) concordance was 62% for CTC≥1 and 73.5% for CTC≥2 (Chi-Square, p=0.161 and p=0.307). Post-chemotherapy, the positivity rate was 33.6% (CTC≥1) and 18.8% (CTC≥2) by CellSearch and 11.6% by RT-PCR (Spearman, R=-0.031, p=0.761). Overall agreement was 60.6% (CTC≥1) and 71.4% (CTC≥2) (Chi-Square, p=0.771 and p=0.708). In the metastatic setting, 37.8% of the samples were positive by RT-PCR, and 50% (CTC≥2) or 32.3% (CTC≥5), by CellSearch (Spearman, R=0.373, p=0.0001). Overall agreement was 70.0% for CTC≥5 (Chi-Square, p=0.0001). Post-chemotherapy, 21% were positive by RT-PCR and 13.7% and 8.4% by CellSearch for CTC≥2 and ≥5, respectively (Spearman, R=0.194, p=0.063). Overall concordance for CTC≥5 was 79.6% (Chi-Square, p=0.017). Agreement was also observed for CTC≥2, pre-and post-chemotherapy (Chi-Square, p=0.0001 and p=0.010). The concordance rates in the adjuvant and metastatic settings are shown in Table 1. Conclusions: A high concordance between the two methods was detected in metastatic but not in early disease. Patient follow-up will determine the clinical relevance of each individual assay or their combination in the assessment of patient prognosis. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-21.</jats:p

Significance of hypocarbia in the development of periventricular leukomalacia in preterm infants

Background: Despite rapid advances in the management of preterm infants, periventricular leukomalacia (PVL) remains a considerable problem in neonatal intensive care. The aim of this study was to determine whether hypocarbia is associated with the development of PVL in mechanically ventilated, preterm infants and to emphasize the importance of avoiding this disturbance. Methods: The authors evaluated 52 mechanically ventilated infants with a gestational age of &lt;34 weeks, who exhibited hypocarbia in the first three postnatal days (lowest carbon dioxide tension being &lt;25 mmHg). These infants were then compared with 52 infants in a control group not exhibiting hypocarbia, matched for birthweight and gestational age. A diagnosis of PVL was made on the basis of the results of cranial ultrasonography. Confounding factors potentially associated with the development of PVL were controlled in logistic regression analyses. Results: Of the 52 mechanically ventilated preterm infants with hypocarbia, 10 (19.2%) developed cystic PVL, and six (11.5%) developed periventricular echodensity. Of the 52 infants in the control group only two (3.8%) developed cystic PVL, and one (1.9%) infant developed periventricular echodensity. The authors observed no significant differences in other prenatal and perinatal risk factors between the two groups. Conclusion: Hypocarbia in mechanically ventilated preterm infants during the first days of life is suggested as being an independent predictor of PVL, predisposing these infants to subsequent neurodevelopmental delay