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BACKGROUND: The 12-gene Oncotype DX Colon Recurrence Score® result quantifies the recurrence risk in stage II/III colon cancer (CC). This real-world study investigated stage II CC patients whose treatment decisions incorporated the Recurrence Score® (RS) result. MATERIALS AND METHODS: This retrospective analysis of a prospectively designed cohort included all stage II, mismatch repair-proficient CC patients who underwent 12-gene testing through Clalit between January 2011 and December 2016 and had available data with a minimum 3-year follow-up. RESULTS: The analysis included 938 patients {median age 68 [interquartile range (IQR) 60-76] years; 96% T3 tumors}. The median RS was 26 (IQR 19-33) and the three RS categories (0-29, 30-40, 41-100) included 65%, 24%, and 11% of patients, respectively. Chemotherapy (CT) use differed significantly between the three RS categories (14%, 36%, and 60%, respectively; P < 0.001). The CT and observation-only groups were imbalanced with worse clinicopathologic characteristics in the former. Among observation-only patients, Kaplan-Meier (KM) estimates for recurrence-free interval (RFI) and CC-specific survival (CCSS) differed significantly between the three RS categories (P < 0.001). Clinical outcomes by treatment (CT versus observation) within each RS category revealed no differences in RFI and CCSS in the RS 0-29 and 30-40 categories. In contrast, in the RS 41-100 category, the difference in RFI trended toward significance (P = 0.066), and for CCSS, a statistically significant difference was observed, with better outcomes among CT-treated patients (P = 0.035). CONCLUSIONS: RS results are prognostic in stage II CC. Among RS 41-100 patients, outcomes were better in CT-treated versus observation-only patients despite worse clinicopathologic characteristics, suggesting that CT confers clinical benefit in high-risk patients.
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BACKGROUND: Treatment options are limited for participants with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) that progressed after two or more prior therapies. Studies have shown that blockade of both lymphocyte-activation gene 3 (LAG-3) and programmed cell death protein 1 (PD-1) can improve antitumor activity. Here, we evaluate the antitumor activity of the LAG-3 antibody favezelimab alone or in combination with pembrolizumab in participants with MSS mCRC. PATIENTS AND METHODS: Eligible participants with MSS PD-1/programmed death-ligand 1 (PD-L1) treatment-naive mCRC that progressed on two or more prior therapies received 800 mg favezelimab, 800 mg favezelimab plus 200 mg pembrolizumab, or 800 mg favezelimab/200 mg pembrolizumab co-formulation, every 3 weeks. The primary endpoint was safety, the secondary endpoint was objective response rate (ORR), and exploratory endpoints included duration of response, progression-free survival (PFS), and overall survival (OS). RESULTS: At the data cut-off date of 23 October 2020, a total of 20 participants received favezelimab alone, 89 received favezelimab plus pembrolizumab (including as favezelimab/pembrolizumab co-formulation); 48 had PD-L1 combined positive score (CPS) ≥1 tumors. At this interim analysis median follow-up was 5.8 months with favezelimab and 6.2 with favezelimab plus pembrolizumab. Treatment-related adverse events (TRAEs) were 65% with favezelimab and 65.2% with favezelimab plus pembrolizumab. Grade ≥3 TRAEs were 15% with favezelimab and 20% with favezelimab plus pembrolizumab. No grade 5 TRAEs occurred. Common TRAEs (≥15%) included fatigue (20.0%), nausea (15.0%) with favezelimab, and fatigue (16.9%) with favezelimab plus pembrolizumab. Confirmed ORR was 6.3% with favezelimab plus pembrolizumab, with median duration of response of 10.6 months (range 5.6-12.7 months), median OS of 8.3 months (95% confidence interval 5.5-12.9 months), and median PFS of 2.1 months (1.9-2.2 months). In an exploratory analysis of PD-L1 CPS ≥1 tumors, the confirmed ORR was 11.1%, median OS was 12.7 months (4.5 to not reached), and median PFS was 2.2 months (1.8-4.2 months) with favezelimab plus pembrolizumab. CONCLUSIONS: Favezelimab with or without pembrolizumab had a manageable safety profile, with no treatment-related deaths. Promising antitumor activity was observed with combination therapy, particularly in participants with PD-L1 CPS ≥1 tumors.
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Antineoplásicos Imunológicos , Neoplasias Colorretais , Humanos , Anticorpos Monoclonais , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fadiga/induzido quimicamente , Inibidores de Checkpoint Imunológico , Repetições de Microssatélites , Receptor de Morte Celular Programada 1RESUMO
BACKGROUND: Numerous studies have assessed the socio-cognitive profile in Williams syndrome (WS) and, independently, in 22q11.2 deletion syndrome (22q11.2DS). Yet, a cross-syndrome comparison of these abilities between individuals with these two syndromes with known social deficits has not been conducted. METHODS: Eighty-two children participated in four study groups: WS (n = 18), 22q112.DS (n = 24), age-matched individuals with idiopathic developmental disability (IDD; n = 20) and typically developing (TD) controls (n = 20). Participants completed four socio-cognitive tests: facial emotion recognition, mental state attribution, differentiating real from apparent emotions and trait inference based on motives and actions-outcomes. RESULTS: The current findings demonstrate that children with WS were better in labelling happy faces compared with children with 22q11.2DS, partially reflecting their exaggerated social drive. In the false belief task, however, the WS and IDD groups performed poorly compared with the 22q11.2DS group, possibly due to their difficulty to interpret subtle social cues. When asked to identify the gap between real-negative vs. apparent-positive emotions, the 22q11.2DS group performed similarly to TD children but better than the WS group, possibly due to their anxious personality and their innate bias towards negatively valence cues. Finally, individuals with WS were more willing to become friends with a story character even when the character's motives were negative, reflecting their difficulty to avoid potentially harmful real-life situations. CONCLUSIONS: Overall, our multi-facet socio-cognitive battery uncovered strengths and weaknesses in social cognition that are syndrome-specific, shared among the genetic syndromes, or common to the three clinical groups compared with healthy controls. Our findings underscore the need to devise age-specific and condition-specific assessment tools and intervention programs towards improving these children's socio-cognitive deficits.
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Deficiências do Desenvolvimento/fisiopatologia , Síndrome de DiGeorge/fisiopatologia , Emoções/fisiologia , Reconhecimento Facial/fisiologia , Percepção Social , Teoria da Mente/fisiologia , Síndrome de Williams/fisiopatologia , Adolescente , Criança , Feminino , Humanos , MasculinoRESUMO
AIM: This study aimed to assess the progression-free and overall survival of patients with residual microscopic disease following neoadjuvant chemoradiotherapy and rectal resection for locally advanced rectal cancer. METHOD: Two-hundred and thirty-four consecutive rectal cancer patients who had neoadjuvant chemoradiotherapy followed by radical resection (from May 2000 to April 2012) were divided according to pathological tumour response: residual microscopic disease (MIC), complete response (pCR) and partial/no response (non-CR). Data on the neoadjuvant regime, treatment-to-surgery interval, final pathology, type of operation, operative time, postoperative complications, length of hospital stay, disease recurrence and mortality were compared between the groups. RESULTS: There were 13 (5.5%) MIC patients, 48 (20.5%) with pCR and 173 (73.9%) with non-CR group. The groups were demographically comparable. MIC patients had more retrieved lymph nodes compared with the non-CR and pCR patients (median 13 compared with 8 and 10, respectively, P = 0.0086). The 5-year overall survival rates were 93.4% for the pCR and MIC patients vs 82.1% for the non-CR patients (P = 0.0324). The 5-year progression-free survival was 85.2% for the pCR and MIC patients vs 73.8% for the non-CR patients (P = 0.086). CONCLUSION: We have identified and assessed a new pathological subgroup of rectal cancer patients who had residual microscopic disease after neoadjuvant therapy. The survival analysis aligned them closely with pCR patients.
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Adenocarcinoma/terapia , Quimiorradioterapia , Procedimentos Cirúrgicos do Sistema Digestório , Terapia Neoadjuvante , Neoplasias Retais/terapia , Reto/cirurgia , Adenocarcinoma/patologia , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Tempo de Internação , Excisão de Linfonodo , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Neoplasia Residual , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To compare echogenicity detected using cranial ultrasound (cUS) and diffuse excessive high signal intensity (DEHSI) detected using magnetic resonance imaging (MRI) by identical region-based scoring criteria in preterm infants. To explore the association between these white matter (WM) signal changes with early neurobehavior. STUDY DESIGN: Forty-nine pre-selected premature infants with only echogenicity on a first routine cUS1 underwent MRI and a repeated cUS2 at term equivalent age. Echogenicity and DEHSI were graded in various brain areas and diffusivity values were calculated. Neurobehavior was assessed using the Rapid Neonatal Neurobehavioral Assessment Procedure. RESULT: WM signal changes were significantly higher on cUS1 than cUS2; and higher in MRI than cUS2 in posterior regions. Infants with DEHSI demonstrated reduced tissue integrity. Imaging findings were not correlated with early neurobehavior. CONCLUSION: Echogenicity and DEHSI likely represent the same phenomenon. Reduction of over-interpretation of WM signal changes may help define criteria for the judicious use of imaging in routine follow-up of premature infants.
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Encéfalo/patologia , Ecoencefalografia/métodos , Recém-Nascido Prematuro , Imageamento por Ressonância Magnética/métodos , Substância Branca/patologia , Comportamento , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
BACKGROUND: In metastatic colorectal cancer (mCRC), KRAS is the only validated biomarker used to select patients for administration of epidermal growth factor receptor (EGFR)-targeted therapies. To identify additional predictive markers, we investigated the importance of HER2, the primary EGFR dimerisation partner, in this particular disease. METHODS: We evaluated the HER2 gene status by fluorescence in situ hybridisation (FISH) in 170 KRAS wild-type mCRC patients treated with cetuximab or panitumumab. RESULTS: Depending on HER2 gene copy number status, patients showed three distinct cytogenetic profiles: 4% of patients had HER2 gene amplification (R:HER2/CEP17 ≥ 2) in all neoplastic cells (HER2-all-A), 61% of patients had HER2 gain due to polysomy or to gene amplification in minor clones (HER2-FISH+*), and 35% of patients had no or slight HER2 gain (HER2-FISH-). These subgroups were significantly correlated with different clinical behaviours, in terms of response rate (RR; P=0.0006), progression-free survival (PFS; P<0.0001) and overall survival (OS; P<0.0001). Patients with HER2-all-A profile experienced the worst outcome, patients with HER2-FISH- profile showed an intermediate behaviour and patients with HER2-FISH+* profile were related to the highest survival probability (median PFS in months: 2.5 vs 3.9 vs 7.6, respectively; median OS in months: 4.2 vs 9.7 vs 13, respectively). CONCLUSION: HER2 gene copy number status may influence the clinical response to anti-EGFR-targeted therapy in mCRC patients.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Dosagem de Genes , Receptor ErbB-2/genética , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Cetuximab , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mutação/genética , Panitumumabe , Prognóstico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Estudos Retrospectivos , Taxa de Sobrevida , Proteínas ras/genéticaRESUMO
OBJECTIVE: To examine long-term behavioral and neurodevelopmental outcome of children born growth restricted and exposed to hypertension in utero at 9 years of age. METHODS: Somatic growth and neurocognitive outcomes were evaluated at age 9-10 years of age in 42 children born with intra uterine growth restriction (IUGR) after pregnancies complicated by hypertensive disorder (17 with maternal preeclampsia and 25 after gestational hypertension). This study group was compared to a control group of 78 IUGR children born after normotensive pregnancy. RESULTS: Only weight was found to be significantly lower in the hypertensive-IUGR group, versus the normotensive IUGR children. No significant differences were found in any of the neurocognitive parameters including IQ, school achievements, and neurodevelopmental score at age 9-10 years. CONCLUSION: IUGR is a well known risk factor for later cognitive difficulties but maternal hypertensive disorder does not seem to add significantly to this risk.
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Desenvolvimento Infantil/fisiologia , Cognição/fisiologia , Retardo do Crescimento Fetal , Recém-Nascido de Baixo Peso , Pré-Eclâmpsia , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Criança , Feminino , Retardo do Crescimento Fetal/diagnóstico , Retardo do Crescimento Fetal/epidemiologia , Retardo do Crescimento Fetal/fisiopatologia , Seguimentos , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão Induzida pela Gravidez/fisiopatologia , Recém-Nascido de Baixo Peso/crescimento & desenvolvimento , Recém-Nascido de Baixo Peso/psicologia , Recém-Nascido , Masculino , Mães/estatística & dados numéricos , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , PrognósticoRESUMO
Well-recognized experts in the field of gastric cancer discussed during the 12th European Society Medical Oncology (ESMO)/World Congress Gastrointestinal Cancer (WCGIC) in Barcelona many important and controversial topics on the diagnosis and management of patients with gastric cancer. This article summarizes the recommendations and expert opinion on gastric cancer. It discusses and reflects on the regional differences in the incidence and care of gastric cancer, the definition of gastro-esophageal junction and its implication for treatment strategies and presents the latest recommendations in the staging and treatment of primary and metastatic gastric cancer. Recognition is given to the need for larger and well-designed clinical trials to answer many open questions.
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Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/terapia , Predisposição Genética para Doença , Humanos , Metástase Neoplásica , Guias de Prática Clínica como Assunto , Prognóstico , Fatores de Risco , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
The article summarizes the expert discussion and recommendations on the use of molecular markers and of biological targeted therapies in metastatic colorectal cancer (mCRC), as well as a proposed treatment decision strategy for mCRC treatment. The meeting was conducted during the 11th ESMO/World Gastrointestinal Cancer Congress (WGICC) in Barcelona in June 2009. The manuscript describes the outcome of an expert discussion leading to an expert recommendation. The increasing knowledge on clinical and molecular markers and the availability of biological targeted therapies have major implications in the optimal management in mCRC.
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Neoplasias Colorretais/tratamento farmacológico , Antineoplásicos/efeitos adversos , Biomarcadores/metabolismo , Antígeno Carcinoembrionário/análise , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Receptores ErbB/antagonistas & inibidores , Humanos , Instabilidade de Microssatélites , Mutação , Metástase Neoplásica , Prognóstico , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Espanha , Proteínas ras/genéticaRESUMO
BACKGROUND: Recent reports showed that children born with intrauterine growth restriction (IUGR) are at greater risk of experiencing verbal short-term memory span (STM) deficits that may impede their learning capacities at school. It is still unknown whether these deficits are modality dependent. METHODS: This long-term, prospective design study examined modality-dependent verbal STM functions in children who were diagnosed at birth with IUGR (n = 138) and a control group (n = 64). Their STM skills were evaluated individually at 9 years of age with four conditions of the Visual-Aural Digit Span Test (VADS; Koppitz, 1981): auditory-oral, auditory-written, visuospatial-oral and visuospatial-written. Cognitive competence was evaluated with the short form of the Wechsler Intelligence Scales for Children--revised (WISC-R95; Wechsler, 1998). RESULTS: We found IUGR-related specific auditory-oral STM deficits (p < .036) in conjunction with two double dissociations: an auditory-visuospatial (p < .014) and an input-output processing distinction (p < .014). Cognitive competence had a significant effect on all four conditions; however, the effect of IUGR on the auditory-oral condition was not overridden by the effect of intelligence quotient (IQ). CONCLUSIONS: Intrauterine growth restriction affects global competence and inter-modality processing, as well as distinct auditory input processing related to verbal STM functions. The findings support a long-term relationship between prenatal aberrant head growth and auditory verbal STM deficits by the end of the first decade of life. Empirical, clinical and educational implications are presented.
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Transtornos Cognitivos/epidemiologia , Retardo do Crescimento Fetal/epidemiologia , Memória de Curto Prazo , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Comportamento Verbal , Estimulação Acústica/métodos , Estimulação Acústica/estatística & dados numéricos , Análise de Variância , Causalidade , Criança , Transtornos Cognitivos/diagnóstico , Comorbidade , Feminino , Seguimentos , Humanos , Israel/epidemiologia , Estudos Longitudinais , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Pais/psicologia , Gravidez , Estudos Prospectivos , Fatores de Risco , Fatores Socioeconômicos , Análise e Desempenho de Tarefas , TempoRESUMO
This study examines long-term effects of antenatal management of intrauterine growth restriction (IUGR) on developmental outcome and on maternal coping using a prospective cross-sectional design. Sixty-nine families were evaluated using psychological testing and risk questionnaires. The effects of timing of diagnosis (prenatal/perinatal) and of pregnancy management [induction of labor (IL)/conservative management (CM)/none, i.e., diagnosed-at-birth (DaB)] on maternal stress were tested at 6 years' postbirth. In general, prenatal management protocols of IUGR were efficient in preventing major disabilities; however, 49% of the variance in maternal stress at 6 years' postbirth could be attributed to the child's presenting behavior and to pregnancy management of IUGR condition. Mothers who received CM treatment reported being more stressed by their child's poor emotional adjustment (ps < .01-.002) and distractibility (p < .029), and to have more difficulty in accepting them (p < .01). Prenatal psychological consultation to better handle stress for parents whose fetus is diagnosed with IUGR is recommended, particularly when pregnancy is managed conservatively and familial-educational resources are low.
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The I1307K APC germline mutation is associated with an increased risk to colo-rectal cancer (CRC). Whether and to what extent the phenotype of CRC in mutation carriers differs from sporadic cases, remains unknown. To gain insight into this issue, we analysed 307 unselected Israeli patients with CRC, who were treated in a single medical centre, for harbouring the I1307K mutation. Twenty-eight mutation carriers (9.1%) were detected. Two of 28 mutation carriers (7.1%) and 93/277 (33.6%) of non-carriers, were of non-Ashkenazi origin (P < 0.01). In 74/278 (26.6%) of the sporadic cases, and only 1/28 (3.6%) of mutation carriers (3.6%) the tumour was located in the right colon (P < 0.01). Mutation carriers had a more advanced disease stage (14/28 - 50% Dukes C), as compared with 60 (19.5%) of non-carriers (P = 0.02). The mean age at diagnosis was similar: 65 (+/- 9.7) years and 66.3 (+/- 11.6) years, for mutation carriers and non-carriers, respectively. No statistical differences were noted between the two groups in sex distribution, tumour grade, and family history of cancer. We conclude that early age at diagnosis and family history of cancer cannot be used to predict who is likely to harbour the I1307K APC germline mutation carriers. However, the tumours in patients with this mutation appear different than those without, are less likely to be proximal and more likely to be advanced than tumours in non-carriers.
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Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Genes APC , Mutação em Linhagem Germinativa/genética , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , DNA de Neoplasias , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Linhagem , Fenótipo , Reação em Cadeia da Polimerase , Fatores SexuaisRESUMO
The genetic basis for the majority of early onset or non-syndromic "familial" colorectal cancer (CRC) is unknown. Attenuated APC phenotype is characterized by relatively few colonic polyps, early age at onset of colon cancer compared with the general population, and inactivating germline mutations within specific regions of the APC gene. We hypothesized that germline mutations within these APC gene regions, might contribute to early onset or familial CRC susceptibility. To test this notion, we analysed 85 Israeli patients with either early onset (< 50 years at diagnosis) or familial CRC for harbouring mutations within the relevant APC gene regions: exons 1-5, exon 9 and a region within exon 15 (spanning nucleotides c.3900 to c.4034; codons 1294 to 1338) using denaturing gradient gel electrophoresis (DGGE), and all of exon 15 employing protein truncation test (PTT). No inactivating, disease-associated mutations were detected in any patient. A novel polymorphism in intron 5 was detected in 16 individuals, 8 patients were carriers of the 11307K variant, a mutation prevalent among Jewish individuals with colorectal cancer, and 4 displayed the E1317Q variant. We conclude that in Israeli individuals with early onset or familial CRC, truncating mutations in the APC gene regions associated with attenuated APC phenotype probably contribute little to disease pathogenesis.
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Pólipos do Colo/genética , Neoplasias Colorretais/genética , Genes APC/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Pólipos do Colo/patologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Israel , Judeus/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo GenéticoRESUMO
Inherited predisposition occurs in 5-10% of all gastrointestinal (GI) cancer patients, but with the exception of colorectal cancer (CRC), the genes involved in conferring genetic susceptibility remain largely unknown. Indirect evidence indicates that germline mutations in BRCA2 might be associated with an increased risk for various GI malignancies. A single mutation (6174delT) occurs in the BRCA2 gene in high-risk breast ovarian cancer families of Jewish Ashkenazi origin, in about 1% of the general Ashkenazi population, and rarely in non-Ashkenazi Jews. In order to assess the contribution of this germline mutation to non-CRC GI cancer in Jewish Israeli patients, we tested 70 unselected, consecutive Jewish Ashkenazi patients with gastrointestinal malignancies for this mutation by PCR amplification and modified restriction enzyme digests. Patients' age range was 38-90 years (mean 65.8+/-11.8 years). The most common malignancies were gastric cancer (n = 35) and exocrine pancreatic cancer (n = 23). Overall, 6 mutation carriers were detected: 3/23 (13%) of the patients with pancreatic cancer, 2/35 (5.7%) of patients with gastric cancer and 1/4 (25%) of patients with bile duct cancer. The 8.6% mutation carrier rate among patients is a rate significantly higher than that of the general Ashkenazi population (1.16%, P = 0.0002). We conclude that the rate of the predominant Jewish BRCA2 mutation in patients with gastric and pancreatic cancer significantly differ from that of the general population of the same ethnic origin. Thus, BRCA2 mutations probably contribute to gastrointestinal tumorigenesis other then colon cancer, and the surveillance scheme for mutation carriers should incorporate this information.
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Neoplasias Gastrointestinais/genética , Predisposição Genética para Doença , Judeus/genética , Proteínas de Neoplasias/genética , Fatores de Transcrição/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA2 , Transformação Celular Neoplásica , Análise Mutacional de DNA , Feminino , Neoplasias Gastrointestinais/etnologia , Genética Populacional , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
The neurodevelopmental and cognitive outcome of long-term Intrauterine Growth Restriction (IUGR) has been followed up from pregnancy to school age at the Tel Aviv Child Development Centre.
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Desenvolvimento Infantil/fisiologia , Retardo do Crescimento Fetal/complicações , Criança , Pré-Escolar , Retardo do Crescimento Fetal/psicologia , Seguimentos , Humanos , Recém-Nascido , Testes de Inteligência , Israel , Estudos Prospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
This prospective study was designed to characterize the neurodevelopmental and cognitive difficulties specific to children with intrauterine growth retardation and to detect early clinical predictors of these difficulties. Eighty-one children with intrauterine growth retardation were monitored up to 6 to 7 years of age using biometric parameters, perinatal risk questionnaires, and detailed neurodevelopmental and cognitive assessments. Forty-one children served as age-matched, appropriate for gestational age controls. A significant difference in growth parameters (P < .001), neurodevelopmental score (P < .05), and IQ (P < .05) was found between the children with intrauterine growth retardation and controls. A specific profile of difficulties in coordination, lateralization, spatial and graphomotor skills, and abundance of associated movements is typical of the children with intrauterine growth retardation and hints at possible later learning disabilities. The clinical parameters best predicting neurodevelopmental outcome were the neonatal risk score (P < .05) and the weight and height at 6 years of age (P < .05). The children with intrauterine growth retardation with neonatal complications had lower neurodevelopmental scores than the controls but no difference in IQ. Intrauterine growth retardation children diagnosed prenatally had the same neurodevelopmental and IQ scores as those diagnosed at birth, probably due to the careful perinatal and obstetric care provided. Children with intrauterine growth retardation demonstrate a specific profile of neurodevelopmental disabilities at preschool age. Early diagnosis and intervention could probably reduce these difficulties to a minimum.
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Transtornos Cognitivos/etiologia , Deficiências do Desenvolvimento/etiologia , Retardo do Crescimento Fetal/complicações , Criança , Pré-Escolar , Crianças com Deficiência , Feminino , Seguimentos , Lateralidade Funcional , Humanos , Testes de Inteligência , Masculino , Transtornos das Habilidades Motoras , Fatores de RiscoRESUMO
Arousal effects on a 1-trial visual recognition paired-comparison task were studied at newborn, 1-month, and 4-month test ages. Infants were tested before and after feeding, with arousal assumed to be lower after feeding. Newborns and 1-month-olds shifted from a familiarity preference before feeding to a novelty preference after feeding. A control group tested only after feeding confirmed that this shift was not due to increased stimulus exposure from the prefeeding test. By 4 months, infants showed novelty preferences independent of feeding. This age by arousal interaction for recognition memory extends previous knowledge by including endogenous arousal with age, stimulus, and length of exposure as contributors to familiarity-novelty preferences. It also extends and provides converging evidence for arousal effects on visual attention in early infancy found previously with preferential looking. A shift from subcortical to cortical dominance is supported.