Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: E...Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: Epidemiological, observational, and cross-sectional, with two cohorts of patients. Settings: IESS Quito Sur Hospital at Quito, Ecuador, from February to April of 2020. Participants: This study included 204 newborns, 102 preterm infants, 102 term infants. Results: There are significant differences between late preterm infants and term infants, with a p-value of 0.000 in the prevalence of early sepsis, 70.59% vs. 35.29%. In respiratory distress syndrome between late and term premature infants, significant differences were observed with a p-value of 0.000, the proportion being 55.58% vs. 24.51% respectively. The prevalence of jaundice is higher in term infants with a p value of 0.002, 72.55%, versus 51.96% in late preterm infants, and the mean value of bilirubins in mg/dL was higher in term infants 14.32 versus 12.33 in late preterm infants;this difference is statistically significant with a p value of 0.004. Admission to the NICU is more frequent in late preterm infants with a p-value of 0.000, being 42.16% for late preterm infants vs. 7.84% in term infants;the mean of the hospital days with p-value 0.005, was higher in late preterm infants 4.97 days vs. 3.55 days for term newborns. Conclusion: Due to the conditions of their immaturity, late preterm infants are 2.86 times more likely to present early sepsis than full-term newborns. It is shown that late preterm infants are 2.69 times more likely to have respiratory distress syndrome compared to term infants, therefore, late preterm infants have a longer hospital stay of 4.97 days versus 3.55 days in term infants. Jaundice and mean bilirubin levels are higher in term infants due to blood group incompatibility and insufficient breastfeeding.展开更多
Background Kaiser Sepsis Calculator(KSC)reduces antibiotic use,testing and intravenous infiltrates but there are concerns about the missed early onset sepsis(EOS)cases.We sought to apply the KSC score for culture-posi...Background Kaiser Sepsis Calculator(KSC)reduces antibiotic use,testing and intravenous infiltrates but there are concerns about the missed early onset sepsis(EOS)cases.We sought to apply the KSC score for culture-positive infants retrospectively in infants born in the last 10 years in our hospital.Methods In a retrospective cohort study,the comparison groups were divided into Group A(no antibiotics recommended by KSC)and Group B(antibiotics recommended).Results Overall,17/24(71%)infants would have been started on antibiotics per KSC but 7/24(29%)would not.The initial EOS risk was not significantly different between the groups(Group A vs.Group B:0.44 vs.0.76,P=0.41),but the final risk score was(0.33 vs.9.41,P<0.001).In Group A(no antibiotics),3/7 infants became symptomatic between 9 and 42 hours.Conclusion There may be a potential delay in starting antibiotics in infants that are asymptomatic at birth while using KSC.展开更多
BACKGROUND Preeclampsia(PE)is a multisystemic metabolic disease with an undetermined etiology.PE is a worldwide cause of maternal and perinatal morbidity,subdivided into early(EoPE)and late-onset(LoPE)according to 34 ...BACKGROUND Preeclampsia(PE)is a multisystemic metabolic disease with an undetermined etiology.PE is a worldwide cause of maternal and perinatal morbidity,subdivided into early(EoPE)and late-onset(LoPE)according to 34 wk of gestation as a divider.Many researchers investigated biomarkers for predicting PE to halt its consequences on the feto-maternal outcome.Elabela(Ela)is a newly discovered peptide hormone that was implicated in PE pathogenesis.Earlier rodent studies discussed Ela’s role in controlling blood pressure.Moreover,Ela deficiency was associated with PE development.AIM To test whether plasma Ela could serve as a reliable marker for predicting PE based on the time of onset(EoPE vs LoPE)compared to age and body mass matched healthy controls since no definitive treatment exists for PE but to terminate a pregnancy.METHODS This case-control study recruited(n=90)pregnant who fulfilled inclusion criteria;they were allocated into three groups:EoPE(30/90)(<34 wk of gestation);LoPE(30/90)(≥34 wk of gestation);and healthy pregnant(30/90).Demographic criteria;biochemical,hematological,and maternal plasma Ela levels were recorded for comparison.RESULTS Serum Ela was significantly reduced in EoPE compared to LoPE and healthy controls(P=0.0023).The correlation confirmed a strong inverse relationship with mean atrial blood pressure(r=-0.7,P<0.001),while gestational age and platelets count showed a moderate correlation with(r=0.4 with P<0.0001).No correlation was confirmed between the body mass index(BMI)and urine albumin.The predictive ability of 25 centile serum Ela had an Odds ratio of 5.21,95%confidence interval(1.28,21.24),P=0.02 for predicting EoPE.The receiver operator characteristic curve defined the Ela cutoff value at>9.156 with 96.7%and 93.3%sensitivity and specificity,P<0.0001 in predicting EoPE.CONCLUSION A strong correlation of serum Ela with PE parameters with excellent sensitivity and specificity in distinguishing EoPE independent of the BMI,age,and blood pressure which makes Ela a recommendable marker in screening.Further research is warranted to explore prognostic and therapeutic applications for Ela in PE.展开更多
Juvenile bipolar disorder can be a challenging diagnosis, given its atypical presentation and tendency to have other comorbid psychiatric disorders. In this case study, we describe a case of a young patient with some ...Juvenile bipolar disorder can be a challenging diagnosis, given its atypical presentation and tendency to have other comorbid psychiatric disorders. In this case study, we describe a case of a young patient with some atypical symptoms of early-onset bipolar disorder.展开更多
BACKGROUND Preeclampsia(PE)is a pregnancy syndrome of undetermined etiology;inflammation was one of the proposed theories for its development.AIM To examine the platelet to lymphocyte ratio(PLR),an inflammatory biomar...BACKGROUND Preeclampsia(PE)is a pregnancy syndrome of undetermined etiology;inflammation was one of the proposed theories for its development.AIM To examine the platelet to lymphocyte ratio(PLR),an inflammatory biomarker,as a marker to predict poor maternal-neonatal outcomes in early-onset PE(EoPE).METHODS A cross-sectional study enrolled 60 pregnant women with EoPE(at 32-30 wk of gestation)at a university hospital.Demographic criteria and hematological indices were collected,including platelet counts and indices(mean platelet volume and platelet distribution width),PLR,and the Doppler study,which calculated estimated fetal weight(EFW),amniotic fluid index(AFI),resistance index(RI),and pulsatility index(PI).Participants were followed until delivery,where maternal outcomes were recorded,including;delivery mode and reason for cesarean section,and neonatal outcomes,including fetal growth restriction(FGR),meconium-stained liquid,the 5-min Apgar score,and admission to the intensive care unit.RESULTS There was a trend of insignificant increases in cesarean sections.Sixty-one-point two percent(37/60)fetuses were admitted to the neonatal care unit;70.0%of admitted fetuses were meconium-stained liquor,and 56.7%of them had FGR.PLR was positively correlated with AFI and EFW as r=0.98,0.97,P<0.001;PLR showed negative correlations with PI and RI as r=-0.99,-0.98,P<0.001.The Apgar score and the number of days admitted to the intensive care unit had a positive and negative correlation(0.69,-0.98),P<0.0001,respectively.Receiver operating characteristic calculated a PLR cutoff value(7.49)that distinguished FGR at 100%sensitivity and 80%specificity.CONCLUSION Strong,meaningful relationships between PLR and FGR parameters and a poor neonatal outcome with a significant P value make it a recommendable biomarker for screening EoPE-related complications.Further studies are suggested to see the impact on maternal-neonatal health.展开更多
Background: Preeclampsia (PE) is one of the forms of hypertensive diseases that occur during pregnancy. Early-onset preeclampsia (EOP), which occurred before 34 weeks, proved to be the deadliest. Indeed, it is charact...Background: Preeclampsia (PE) is one of the forms of hypertensive diseases that occur during pregnancy. Early-onset preeclampsia (EOP), which occurred before 34 weeks, proved to be the deadliest. Indeed, it is characterized by a poor maternal and fetal prognosis. EOP has a disparate incidence in the world varying between 0.9% and 31%. Several risks factors are associated with the occurrence of EOP, which is responsible of several adverse obstetrical outcomes. Complications can affect up to 85% of pregnant women with EOP, especially when EOP appears very early, before 28 or even 25 weeks’ gestation. Objectives: To determine frequency of EOP at the University Clinics of Kinshasa, to describe sociodemographic and clinical characteristics of pregnant women with EOP and to identify its risks factors and its association adverse obstetrical outcomes. Methods: The study will be a cross-sectional analytical study in University Clinics of Kinshasa from January 2016 to December 2022. The minimal size will be 119. Our study population will consist of pregnant women who consult for antenatal best care and are neonates in our Clinic. Result will be presented as percentage proportion. Comparison and proportion means between groups will be made using Student’s test and Pearson’s chi-square test, respectively. Our test will be statistically significant for a p-value ≤ than less 0.05. Data will be collected and analysed anonymously and confidentiality. Conclusion: We believe that our study should enable us to identify profile of gestational carriers at risk of EOP in our environment, as well as prognosis associated with this entity, with a view to arousing particular interest in EOP.展开更多
BACKGROUND Currently, it is difficult to predict the complications of children at the early stage of sepsis. Brighton pediatric early warning score(PEWS) is a disease risk assessment system that is simple and easy to ...BACKGROUND Currently, it is difficult to predict the complications of children at the early stage of sepsis. Brighton pediatric early warning score(PEWS) is a disease risk assessment system that is simple and easy to operate, which has good sensitivity and specificity in disease recognition among children. Because detection indicators vary widely in children, a single indicator is difficult to assess the posttreatment status of children with sepsis.AIM To investigate the relationship between serological markers, Brighton PEWS, and death in children with sepsis after treatment.METHODS A total of 205 children diagnosed with sepsis at our hospital were enrolled. The baseline data, serum scores, and PEWS scores were recorded. In the nested casecontrol study, children who died during the study period were included in an observation group. According to the matching principle, the children who were not dead in the same cohort were included in a control group. The influencing factors of death in children with sepsis after treatment and the value of each evaluation index in predicting the prognosis of children were analyzed.RESULTS A total of 96 children were enrolled in the study, including 48 each in the observation group and the control group. Multivariate logistic regression analysis indicated that antibacterial treatments within 1 h(P = 0.017), shock(P = 0.044),multiple organ dysfunction syndrome(MODS)(P = 0.027), serum procalcitonin(PCT)(P = 0.047), serum albumin(ALB)(P = 0.024), and PEWS(P = 0.012) were independent risk factors for the death of children with sepsis. The area under the curve of the combination of ALB, PCT, and PEWS to predict the death in children with sepsis was the highest(0.908).CONCLUSION Antibacterial treatments within 1 h, shock, MODS, PCT, ALB, and PEWS are independent risk factors for the death of children with sepsis. The predictive accuracy of the combination of PCT, ALB, and PEWS for the prognosis of children with sepsis is the best.展开更多
AIM:To characterize clinicopathological and familial features of early-onset colorectal cancer(CRC) and compare features of tumors with and without microsatellite instability(MSI).METHODS:Forty-five patients with CRC ...AIM:To characterize clinicopathological and familial features of early-onset colorectal cancer(CRC) and compare features of tumors with and without microsatellite instability(MSI).METHODS:Forty-five patients with CRC aged 45 or younger were included in the study.Clinical information,a three-generation family history,and tumor samples were obtained.MSI status was analyzed and mismatch repair genes were examined in the MSI families.Tumors were included in a tissue microarray and an immunohistochemical study was carried out with a panel of selected antibodies.RESULTS:Early onset CRC is characterized by advanced stage at diagnosis,right colon location,low-grade of differentiation,mucin production,and presence of polyps.Hereditary forms represent at least 21% of cases.Eighty-one percent of patients who died during followup showed a lack of expression of cyclin E,which could be a marker of poor prognosis.β-catenin expression was normal in a high percentage of tumors.CONCLUSION:Early-onset CRC has an important familial component,with a high proportion of tumors showing microsatellite stable.Cyclin E might be a poor prognosis factor.展开更多
AIM: To measure the forces applied during distraction of growing-rods in early onset scoliosis(EOS), aimed at developing a motorized elongation device.METHODS: A consecutive series of measurements were carried out to ...AIM: To measure the forces applied during distraction of growing-rods in early onset scoliosis(EOS), aimed at developing a motorized elongation device.METHODS: A consecutive series of measurements were carried out to analyze the forces applied by the surgeon during distraction of single growing-rods in 10 patients affected by EOS(mean age 8.3 years; range 6 to 10 years) undergoing the first distraction 6 months following implantation of the rods. For each measurement, output from the transducer of a dedicated pair of distraction calipers was recorded at zero load status and at every 1 mm of distraction, up to a maximum of 12 mm for each of the two connected rods.RESULTS: Twenty measurements were obtained showing a linear increase of the load with increasing distraction, with a mean peak force of 485 N at 12 mm distraction and a single reading over 500 N. We did not observe bone fractures or ligament disruptions during or after rod elongations. There was one case of superficial wound infection in the cohort.CONCLUSION: The safe peak force carrying capacity of a motorized device for distraction of growing-rods is 500 N.展开更多
Objective Very early-onset coronary artery disease(CAD) is a great challenge in cardiovascular medicine throughout the world,especially regarding its early diagnosis.This study explored whether circulating micro RNAs(...Objective Very early-onset coronary artery disease(CAD) is a great challenge in cardiovascular medicine throughout the world,especially regarding its early diagnosis.This study explored whether circulating micro RNAs(mi RNAs) could be used as potential biomarkers for patients with very early-onset CAD.Methods We performed an initial screening of mi RNA expression using RNA isolated from 20 patients with angiographically documented very early-onset CAD and 20 age-and sex-matched normal controls.For further confirmation,we prospectively examined the mi RNAs selected from 40 patients with very early-onset CAD and 40 angiography-normal controls.Results A total of 22 overexpressed mi RNAs and 22 underexpressed mi RNAs were detected in the initial screening.RT-q PCR analysis of the mi RNAs obtained from the initial screening revealed that four mi RNAs including mi R-196-5p,mi R-3163-3p,mi R-145-3p,and mi R-190a-5p exhibited significantly decreased expression in patients compared with that in controls(P<0.05).The areas under the receiver operating characteristic curve for these mi RNAs were 0.824(95% CI,0.731-0.917;P<0.001),0.758(95% CI,0.651-0.864;P<0.001),0.753(95% CI,0.643-0.863;P<0.001),and 0.782(95% CI,0.680-0.884;P<0.001),respectively,in the validation set.Conclusion To our knowledge,this is an advanced study to report about four serum mi RNAs(mi R-196-5p,mi R-3163-3p,mi R-145-3p,and mi R-190a-5p) that could be used as novel biomarkers for the diagnosis of very early-onset CAD.展开更多
Colorectal cancer is the third most common cancer diagnosed worldwide.Although epidemiology data show a marked variability around the world,its overall incidence rate shows a slow but steady decrease,mainly in develop...Colorectal cancer is the third most common cancer diagnosed worldwide.Although epidemiology data show a marked variability around the world,its overall incidence rate shows a slow but steady decrease,mainly in developed countries.Conversely,early-onset colorectal cancer appears to display an opposite trend with an overall prevalence in United States and European Union ranging from 3.0% and 8.6%.Colorectal cancer has a substantial proportion of familial cases.In particular,early age at onset is especially suggestive of hereditary predisposition.The clinicopathological and molecular features of colorectal cancer cases show a marked heterogeneity not only between early- and late-onset cases but also within the early-onset group.Two distinct subtypes of early-onset colorectal cancers can be identified:a "sporadic" subtype,usually without family history,and an inherited subtype arising in the context of well defined hereditary syndromes.The pathogenesis of the early-onset disease is substantially well characterized in the inherited subtype,which is mainly associated to the Lynch syndrome and occasionally to other rare mendelian diseases,whereas in the "sporadic" subtype the origin of the disease may be attributed to the presence of various common/rare genetic variants,so far largely unidentified,displaying variable penetrance.These variants are thought to act cumulatively to increase the risk of colorectal cancer,and presumably to also anticipate its onset.Efforts are ongoing in the attempt to unravel the intricate genetic basis of this "sporadic" early-onset disease.A better knowledge of molecular entities and pathways may impact on family-tailored prevention and clinical management strategies.展开更多
Colorectal cancer(CRC) is the third most frequent cancer type and the incidence of this disease is increasing gradually per year in individuals younger than 50 years old. The current knowledge is that early-onset CRC(...Colorectal cancer(CRC) is the third most frequent cancer type and the incidence of this disease is increasing gradually per year in individuals younger than 50 years old. The current knowledge is that early-onset CRC(EOCRC) cases are heterogeneous population that includes both hereditary and sporadic forms of the CRC. Although EOCRC cases have some distinguishing clinical and pathological features than elder age CRC, the molecular mechanism underlying the EOCRC is poorly clarified. Given the significance of CRC in the world of medicine, the present review will focus on the recent knowledge in the molecular basis of genetic and epigenetic mechanism of the hereditary forms of EOCRC, which includes Lynch syndrome, Familial CRC type X, Familial adenomatous polyposis, Mut YH-associated polyposis, Juvenile polyposis syndrome, Peutz-Jeghers Syndrome and sporadic forms of EOCRC. Recent findings about molecular genetics and epigenetic basis of EOCRC gave rise to new alternative therapy protocols. Although exact diagnosis of these cases still remains complicated, the present review paves way for better predictions and contributes to more accurate diagnostic and therapeutic strategies into clinical approach.展开更多
AIM: To perform sequencing analysis in patients with very early-onset inflammatory bowel disease(VEO-IBD) to determine the genetic basis for VEO-IBD in Chinese pediatric patients.METHODS: A total of 13 Chinese pediatr...AIM: To perform sequencing analysis in patients with very early-onset inflammatory bowel disease(VEO-IBD) to determine the genetic basis for VEO-IBD in Chinese pediatric patients.METHODS: A total of 13 Chinese pediatric patients with VEO-IBD were diagnosed from May 2012 and August 2014. The relevant clinical characteristics of these patients were analyzed. Then DNA in the peripheral blood from patients was extracted. Next generation sequencing(NGS) based on an IlluminaMiseq platform was used to analyze the exons in the coding regions of 10 candidate genes: IL-10, IL-10 RA, IL-10 RB, NOD2, FUT2, IL23 R, GPR35, GPR65, TNFSF15, and ADAM30. The Sanger sequencing was used to verify the variations detected in NGS.RESULTS: Out of the 13 pediatric patients, ten were diagnosed with Crohn's disease, and three diagnosed with ulcerative colitis. Mutations in IL-10 RA and IL-10 RB were detected in five patients. There were four patients who had single nucleotide polymorphisms associated with IBD. Two patients had IL-10 RA andFUT2 polymorphisms, and two patients had IL-10 RB and FUT2 polymorphisms. Gene variations were not found in the rest four patients. Children with mutations had lower percentile body weight(1.0% vs 27.5%, P = 0.002) and hemoglobin(87.4 g/L vs 108.5 g/L, P = 0.040) when compared with children without mutations. Although the age of onset was earlier, height was shorter, and the response to treatment was poorer in the mutation group, there was no significant difference in these factors between groups.CONCLUSION: IL-10 RA and IL-10 RB mutations are common in Chinese children with VEO-IBD. Patients with mutations have an earlier disease onset, lower body weight and hemoglobin, and poorer prognosis.展开更多
Essential meiotic endonuclease 1 homolog 1 (EME1) is a key DNA repair protein that participates in the recognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomic in...Essential meiotic endonuclease 1 homolog 1 (EME1) is a key DNA repair protein that participates in the recognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomic instability and thus contribute to tumorgenesis. We hypothesized that the exon variants of EME1 confer genetic susceptibility to breast cancer. In a case-control study of 748 breast cancer patients and 778 normal controls, we analyzed the association between two exon variants of EME1 (i.e.,Ile350Thr: rs12450550T>C and Glu69Asp: rs3760413T>G) and breast cancer risk. We found that compared to the common Ile/Ile genotype, the Thr variant genotypes (Thr/Ile+Thr/Thr) conferred a 1.47-fold increased risk of breast cancer (OR=1.47, 95% CI=1.13-1.92). The variant Ile350Thr was also associated with early onset of breast cancer (r=-0.116, P=0.002). The mean age of onset was 44.4 years for Thr/Thr genotype carriers and 46.5 years for Thr/Ile genotype carriers, which was significantly lower than that (49.4 years) for Ile/Ile genotype carriers (P=0.006). Moreover, no significant association was observed between the Glu69Asp variant and breast cancer risk. Our findings suggest that the EME1 variant Ile350Thr contributes to an increased risk and early onset of breast cancer.展开更多
There is by no means a clear-cut pattern of mutations contributing to gastric cancers,and gastric cancer research can be hampered by the diversity of factors that can induce gastric cancer,such as Helicobacter pylori ...There is by no means a clear-cut pattern of mutations contributing to gastric cancers,and gastric cancer research can be hampered by the diversity of factors that can induce gastric cancer,such as Helicobacter pylori infection,diet,ageing and other environmental factors.Tumours are unquestionably riddled with genetic changes yet we are faced with an unsolvable puzzle with respect to a temporal relationship.It is postulated that inherited genetic factors may be more important in early-onset gastric cancer (EOGC) than in gastric cancers found in older patients as they have less exposure to environmental carcinogens.EOGC,therefore,could provide a key to unravelling the genetic changes in gastric carcinogenesis.Gastric cancers occurring in young patients provide an ideal background on which to try and uncover the initiating stages of gastric carcinogenesis.This review summarizes the literature regarding EOGC and also presents evidence that these cancers have a unique molecular-genetic phenotype,distinct from conventional gastric cancer.展开更多
Colorectal cancer(CRC)has a great impact on the world population.With increasing frequency,CRC is described according to the presenting phenotype,based on its molecular characteristics.Classification of CRC tumors acc...Colorectal cancer(CRC)has a great impact on the world population.With increasing frequency,CRC is described according to the presenting phenotype,based on its molecular characteristics.Classification of CRC tumors according to their genetic and/or epigenetic alterations is not only important for establishing the molecular bases of the disease,but also for predicting patient outcomes and developing more individualized treatments.Early-onset CRC is a heterogeneous disease,with a strong familial component,although the disease is sporadic in an important proportion of cases.Different molecular alterations appear to contribute to the apparent heterogeneity of the early-onset population and subgroups can be distinguished with distinct histopathologic and familial characteristics.Moreover,compared with late-onset CRC,there are characteristicsthat suggest that early-onset CRC may have a different molecular basis.The purpose of this review was to analyze the current state of knowledge about earlyonset CRC with respect to clinicopathologic,familial and molecular features.Together,these features make it increasingly clear that this subset of CRC may be a separate disease,although it has much in common with late-onset CRC.展开更多
BACKGROUND Colorectal cancer(CRC)is the second leading cause of all cancer related deaths in the United States and Europe.Although the incidence has been decreasing for individuals’≥50,it has been on the rise for in...BACKGROUND Colorectal cancer(CRC)is the second leading cause of all cancer related deaths in the United States and Europe.Although the incidence has been decreasing for individuals’≥50,it has been on the rise for individuals<50.AIM To identify potential risk factors for early-onset CRC.METHODS A population-based cohort analysis using a national database,Explorys,screened all patients with an active electronic medical record from January 2012 to December 2016 with a diagnosis of CRC.Subgroups were stratified based on age(25–49 years vs≥50 years).Demographics,comorbidities,and symptom profiles were recorded and compared between both age groups.Furthermore,the younger group was also compared with a control group consisting of individuals aged 25-49 years within the same timeframe without a diagnosis of CRC.Twentydata points for CRC related factors were analyzed to identify potential risk factors specific to early-onset CRC.RESULTS A total of 68860 patients were identified with CRC,of which 5710(8.3%)were younger than 50 years old,with 4140(73%)between 40-49 years of age.Multivariable analysis was reported using odds ratio(OR)with 95%CI and demonstrated that several factors were associated with an increased risk of CRC in the early-onset group versus the later-onset group.These factors included:African-American race(OR 1.18,95%CI:1.09-1.27,P<0.001),presenting symptoms of abdominal pain(OR 1.82,95%CI:1.72-1.92,P<0.001),rectal pain(OR 1.50,95%CI:1.28-1.77,P<0.001),altered bowel function(OR 1.12,95%CI:1.05-1.19,P=0.0005),having a family history of any cancer(OR 1.78,95%CI:1.67-1.90,P<0.001),gastrointestinal(GI)malignancy(OR 2.36,95%CI:2.18-2.55,P<0.001),polyps(OR 1.41,95%CI:1.08-1.20,P<0.001),and obesity(OR 1.14,95%CI:1.08-1.20,P<0.001).Comparing the early-onset cohort versus the control group,factors that were associated with an increased risk of CRC were:male gender(OR 1.34,95%CI:1.27-1.41),P<0.001),Caucasian(OR 1.48,95%CI:1.40-1.57,P<0.001)and African-American race(OR 1.25,95%CI:1.17-1.35,P<0.001),presenting symptoms of abdominal pain(OR 4.73,95%CI:4.49-4.98,P<0.001),rectal pain(OR 7.48,95%CI:6.42-8.72,P<0.001),altered bowel function(OR 5.51,95%CI:5.19-5.85,P<0.001),rectal bleeding(OR 9.83,95%CI:9.12-10.6,P<0.001),weight loss(OR 7.43,95%CI:6.77-8.15,P<0.001),having a family history of cancer(OR 11.66,95%CI:10.97-12.39,P<0.001),GI malignancy(OR 28.67,95%CI:26.64-30.86,P<0.001),polyps(OR 8.15,95%CI:6.31-10.52,P<0.001),tobacco use(OR 2.46,95%CI:2.33-2.59,P<0.001),alcohol use(OR 1.71,95%CI:1.62-1.80,P<0.001),presence of colitis(OR 4.10,95%CI:3.79-4.43,P<0.001),and obesity(OR 2.88,95%CI:2.74-3.04,P<0.001).CONCLUSION Pending further investigation,these potential risk factors should lower the threshold of suspicion for early CRC and potentially be used to optimize guidelines for early screening.展开更多
Mutation of the DYT1 gene has been reported to cause early-onset primary torsion dystonia (DYT1).Due to DYT1 gene mutation,defective wild torsinA and the accumulation of mutant torsinA (GAG-deleted DYT1 gene encoded t...Mutation of the DYT1 gene has been reported to cause early-onset primary torsion dystonia (DYT1).Due to DYT1 gene mutation,defective wild torsinA and the accumulation of mutant torsinA (GAG-deleted DYT1 gene encoded the mutant torsinA,torsinA?E) play an important role in DYT1 pathogenesis.Intracellular inclusion bodies are formed,and dopamine transport and release are disturbed by interfering functions of endoplasmic reticulum,nuclear membrane,and cytoskeleton of neural cells,resulting in DYT1 onset.Small interfering RNA could serve as a potential therapy for DYT1.However,the exact function of wild torsinA and the pathological effects of torsinA?E require further studies.展开更多
Currently, gastric cancer(GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possi...Currently, gastric cancer(GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the procarcinogenic activity of important genes. These factors include genetic susceptibility expressed in a singlenucleotide polymorphism, various acquired mutations(chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances(e.g., helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma(EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesisare modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC.展开更多
文摘Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: Epidemiological, observational, and cross-sectional, with two cohorts of patients. Settings: IESS Quito Sur Hospital at Quito, Ecuador, from February to April of 2020. Participants: This study included 204 newborns, 102 preterm infants, 102 term infants. Results: There are significant differences between late preterm infants and term infants, with a p-value of 0.000 in the prevalence of early sepsis, 70.59% vs. 35.29%. In respiratory distress syndrome between late and term premature infants, significant differences were observed with a p-value of 0.000, the proportion being 55.58% vs. 24.51% respectively. The prevalence of jaundice is higher in term infants with a p value of 0.002, 72.55%, versus 51.96% in late preterm infants, and the mean value of bilirubins in mg/dL was higher in term infants 14.32 versus 12.33 in late preterm infants;this difference is statistically significant with a p value of 0.004. Admission to the NICU is more frequent in late preterm infants with a p-value of 0.000, being 42.16% for late preterm infants vs. 7.84% in term infants;the mean of the hospital days with p-value 0.005, was higher in late preterm infants 4.97 days vs. 3.55 days for term newborns. Conclusion: Due to the conditions of their immaturity, late preterm infants are 2.86 times more likely to present early sepsis than full-term newborns. It is shown that late preterm infants are 2.69 times more likely to have respiratory distress syndrome compared to term infants, therefore, late preterm infants have a longer hospital stay of 4.97 days versus 3.55 days in term infants. Jaundice and mean bilirubin levels are higher in term infants due to blood group incompatibility and insufficient breastfeeding.
基金supported by the Chinese-Norwegian Collaboration Projects within Climate Systems jointly funded by the National Key Research and Development Program of China[grant number 2022YFE0106800]the National Natural Science Foundation of China[grant number 42088101]+1 种基金a Research Council of Norway funded project(MAPARC)[grant number 328943]the Innovation Group Project of the Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)[grant number 311020001].
文摘Background Kaiser Sepsis Calculator(KSC)reduces antibiotic use,testing and intravenous infiltrates but there are concerns about the missed early onset sepsis(EOS)cases.We sought to apply the KSC score for culture-positive infants retrospectively in infants born in the last 10 years in our hospital.Methods In a retrospective cohort study,the comparison groups were divided into Group A(no antibiotics recommended by KSC)and Group B(antibiotics recommended).Results Overall,17/24(71%)infants would have been started on antibiotics per KSC but 7/24(29%)would not.The initial EOS risk was not significantly different between the groups(Group A vs.Group B:0.44 vs.0.76,P=0.41),but the final risk score was(0.33 vs.9.41,P<0.001).In Group A(no antibiotics),3/7 infants became symptomatic between 9 and 42 hours.Conclusion There may be a potential delay in starting antibiotics in infants that are asymptomatic at birth while using KSC.
基金approved by the Scientific-Ethical Committee of the Mustansiriyah University(Approval No.IRB126).
文摘BACKGROUND Preeclampsia(PE)is a multisystemic metabolic disease with an undetermined etiology.PE is a worldwide cause of maternal and perinatal morbidity,subdivided into early(EoPE)and late-onset(LoPE)according to 34 wk of gestation as a divider.Many researchers investigated biomarkers for predicting PE to halt its consequences on the feto-maternal outcome.Elabela(Ela)is a newly discovered peptide hormone that was implicated in PE pathogenesis.Earlier rodent studies discussed Ela’s role in controlling blood pressure.Moreover,Ela deficiency was associated with PE development.AIM To test whether plasma Ela could serve as a reliable marker for predicting PE based on the time of onset(EoPE vs LoPE)compared to age and body mass matched healthy controls since no definitive treatment exists for PE but to terminate a pregnancy.METHODS This case-control study recruited(n=90)pregnant who fulfilled inclusion criteria;they were allocated into three groups:EoPE(30/90)(<34 wk of gestation);LoPE(30/90)(≥34 wk of gestation);and healthy pregnant(30/90).Demographic criteria;biochemical,hematological,and maternal plasma Ela levels were recorded for comparison.RESULTS Serum Ela was significantly reduced in EoPE compared to LoPE and healthy controls(P=0.0023).The correlation confirmed a strong inverse relationship with mean atrial blood pressure(r=-0.7,P<0.001),while gestational age and platelets count showed a moderate correlation with(r=0.4 with P<0.0001).No correlation was confirmed between the body mass index(BMI)and urine albumin.The predictive ability of 25 centile serum Ela had an Odds ratio of 5.21,95%confidence interval(1.28,21.24),P=0.02 for predicting EoPE.The receiver operator characteristic curve defined the Ela cutoff value at>9.156 with 96.7%and 93.3%sensitivity and specificity,P<0.0001 in predicting EoPE.CONCLUSION A strong correlation of serum Ela with PE parameters with excellent sensitivity and specificity in distinguishing EoPE independent of the BMI,age,and blood pressure which makes Ela a recommendable marker in screening.Further research is warranted to explore prognostic and therapeutic applications for Ela in PE.
文摘Juvenile bipolar disorder can be a challenging diagnosis, given its atypical presentation and tendency to have other comorbid psychiatric disorders. In this case study, we describe a case of a young patient with some atypical symptoms of early-onset bipolar disorder.
基金the ethical committee of Mustansiriyah University(No.160).
文摘BACKGROUND Preeclampsia(PE)is a pregnancy syndrome of undetermined etiology;inflammation was one of the proposed theories for its development.AIM To examine the platelet to lymphocyte ratio(PLR),an inflammatory biomarker,as a marker to predict poor maternal-neonatal outcomes in early-onset PE(EoPE).METHODS A cross-sectional study enrolled 60 pregnant women with EoPE(at 32-30 wk of gestation)at a university hospital.Demographic criteria and hematological indices were collected,including platelet counts and indices(mean platelet volume and platelet distribution width),PLR,and the Doppler study,which calculated estimated fetal weight(EFW),amniotic fluid index(AFI),resistance index(RI),and pulsatility index(PI).Participants were followed until delivery,where maternal outcomes were recorded,including;delivery mode and reason for cesarean section,and neonatal outcomes,including fetal growth restriction(FGR),meconium-stained liquid,the 5-min Apgar score,and admission to the intensive care unit.RESULTS There was a trend of insignificant increases in cesarean sections.Sixty-one-point two percent(37/60)fetuses were admitted to the neonatal care unit;70.0%of admitted fetuses were meconium-stained liquor,and 56.7%of them had FGR.PLR was positively correlated with AFI and EFW as r=0.98,0.97,P<0.001;PLR showed negative correlations with PI and RI as r=-0.99,-0.98,P<0.001.The Apgar score and the number of days admitted to the intensive care unit had a positive and negative correlation(0.69,-0.98),P<0.0001,respectively.Receiver operating characteristic calculated a PLR cutoff value(7.49)that distinguished FGR at 100%sensitivity and 80%specificity.CONCLUSION Strong,meaningful relationships between PLR and FGR parameters and a poor neonatal outcome with a significant P value make it a recommendable biomarker for screening EoPE-related complications.Further studies are suggested to see the impact on maternal-neonatal health.
文摘Background: Preeclampsia (PE) is one of the forms of hypertensive diseases that occur during pregnancy. Early-onset preeclampsia (EOP), which occurred before 34 weeks, proved to be the deadliest. Indeed, it is characterized by a poor maternal and fetal prognosis. EOP has a disparate incidence in the world varying between 0.9% and 31%. Several risks factors are associated with the occurrence of EOP, which is responsible of several adverse obstetrical outcomes. Complications can affect up to 85% of pregnant women with EOP, especially when EOP appears very early, before 28 or even 25 weeks’ gestation. Objectives: To determine frequency of EOP at the University Clinics of Kinshasa, to describe sociodemographic and clinical characteristics of pregnant women with EOP and to identify its risks factors and its association adverse obstetrical outcomes. Methods: The study will be a cross-sectional analytical study in University Clinics of Kinshasa from January 2016 to December 2022. The minimal size will be 119. Our study population will consist of pregnant women who consult for antenatal best care and are neonates in our Clinic. Result will be presented as percentage proportion. Comparison and proportion means between groups will be made using Student’s test and Pearson’s chi-square test, respectively. Our test will be statistically significant for a p-value ≤ than less 0.05. Data will be collected and analysed anonymously and confidentiality. Conclusion: We believe that our study should enable us to identify profile of gestational carriers at risk of EOP in our environment, as well as prognosis associated with this entity, with a view to arousing particular interest in EOP.
文摘BACKGROUND Currently, it is difficult to predict the complications of children at the early stage of sepsis. Brighton pediatric early warning score(PEWS) is a disease risk assessment system that is simple and easy to operate, which has good sensitivity and specificity in disease recognition among children. Because detection indicators vary widely in children, a single indicator is difficult to assess the posttreatment status of children with sepsis.AIM To investigate the relationship between serological markers, Brighton PEWS, and death in children with sepsis after treatment.METHODS A total of 205 children diagnosed with sepsis at our hospital were enrolled. The baseline data, serum scores, and PEWS scores were recorded. In the nested casecontrol study, children who died during the study period were included in an observation group. According to the matching principle, the children who were not dead in the same cohort were included in a control group. The influencing factors of death in children with sepsis after treatment and the value of each evaluation index in predicting the prognosis of children were analyzed.RESULTS A total of 96 children were enrolled in the study, including 48 each in the observation group and the control group. Multivariate logistic regression analysis indicated that antibacterial treatments within 1 h(P = 0.017), shock(P = 0.044),multiple organ dysfunction syndrome(MODS)(P = 0.027), serum procalcitonin(PCT)(P = 0.047), serum albumin(ALB)(P = 0.024), and PEWS(P = 0.012) were independent risk factors for the death of children with sepsis. The area under the curve of the combination of ALB, PCT, and PEWS to predict the death in children with sepsis was the highest(0.908).CONCLUSION Antibacterial treatments within 1 h, shock, MODS, PCT, ALB, and PEWS are independent risk factors for the death of children with sepsis. The predictive accuracy of the combination of PCT, ALB, and PEWS for the prognosis of children with sepsis is the best.
基金Supported by The Instituto de Salud Carlos Ⅲ, Ministerio de Sanidad y Consumo (FIS01-04, project P047-04)
文摘AIM:To characterize clinicopathological and familial features of early-onset colorectal cancer(CRC) and compare features of tumors with and without microsatellite instability(MSI).METHODS:Forty-five patients with CRC aged 45 or younger were included in the study.Clinical information,a three-generation family history,and tumor samples were obtained.MSI status was analyzed and mismatch repair genes were examined in the MSI families.Tumors were included in a tissue microarray and an immunohistochemical study was carried out with a panel of selected antibodies.RESULTS:Early onset CRC is characterized by advanced stage at diagnosis,right colon location,low-grade of differentiation,mucin production,and presence of polyps.Hereditary forms represent at least 21% of cases.Eighty-one percent of patients who died during followup showed a lack of expression of cyclin E,which could be a marker of poor prognosis.β-catenin expression was normal in a high percentage of tumors.CONCLUSION:Early-onset CRC has an important familial component,with a high proportion of tumors showing microsatellite stable.Cyclin E might be a poor prognosis factor.
文摘AIM: To measure the forces applied during distraction of growing-rods in early onset scoliosis(EOS), aimed at developing a motorized elongation device.METHODS: A consecutive series of measurements were carried out to analyze the forces applied by the surgeon during distraction of single growing-rods in 10 patients affected by EOS(mean age 8.3 years; range 6 to 10 years) undergoing the first distraction 6 months following implantation of the rods. For each measurement, output from the transducer of a dedicated pair of distraction calipers was recorded at zero load status and at every 1 mm of distraction, up to a maximum of 12 mm for each of the two connected rods.RESULTS: Twenty measurements were obtained showing a linear increase of the load with increasing distraction, with a mean peak force of 485 N at 12 mm distraction and a single reading over 500 N. We did not observe bone fractures or ligament disruptions during or after rod elongations. There was one case of superficial wound infection in the cohort.CONCLUSION: The safe peak force carrying capacity of a motorized device for distraction of growing-rods is 500 N.
基金partially supported by the National Natural Science Foundation of China(81070171,81241121)the Specialized Research Fund for the Doctoral Program of Higher Education of China(20111106110013)+2 种基金the Capital Special Foundation of Clinical Application Research(Z121107001012015)the Capital Health Development Fund(2011400302)the Beijing Natural Science Foundation(7131014)
文摘Objective Very early-onset coronary artery disease(CAD) is a great challenge in cardiovascular medicine throughout the world,especially regarding its early diagnosis.This study explored whether circulating micro RNAs(mi RNAs) could be used as potential biomarkers for patients with very early-onset CAD.Methods We performed an initial screening of mi RNA expression using RNA isolated from 20 patients with angiographically documented very early-onset CAD and 20 age-and sex-matched normal controls.For further confirmation,we prospectively examined the mi RNAs selected from 40 patients with very early-onset CAD and 40 angiography-normal controls.Results A total of 22 overexpressed mi RNAs and 22 underexpressed mi RNAs were detected in the initial screening.RT-q PCR analysis of the mi RNAs obtained from the initial screening revealed that four mi RNAs including mi R-196-5p,mi R-3163-3p,mi R-145-3p,and mi R-190a-5p exhibited significantly decreased expression in patients compared with that in controls(P<0.05).The areas under the receiver operating characteristic curve for these mi RNAs were 0.824(95% CI,0.731-0.917;P<0.001),0.758(95% CI,0.651-0.864;P<0.001),0.753(95% CI,0.643-0.863;P<0.001),and 0.782(95% CI,0.680-0.884;P<0.001),respectively,in the validation set.Conclusion To our knowledge,this is an advanced study to report about four serum mi RNAs(mi R-196-5p,mi R-3163-3p,mi R-145-3p,and mi R-190a-5p) that could be used as novel biomarkers for the diagnosis of very early-onset CAD.
文摘Colorectal cancer is the third most common cancer diagnosed worldwide.Although epidemiology data show a marked variability around the world,its overall incidence rate shows a slow but steady decrease,mainly in developed countries.Conversely,early-onset colorectal cancer appears to display an opposite trend with an overall prevalence in United States and European Union ranging from 3.0% and 8.6%.Colorectal cancer has a substantial proportion of familial cases.In particular,early age at onset is especially suggestive of hereditary predisposition.The clinicopathological and molecular features of colorectal cancer cases show a marked heterogeneity not only between early- and late-onset cases but also within the early-onset group.Two distinct subtypes of early-onset colorectal cancers can be identified:a "sporadic" subtype,usually without family history,and an inherited subtype arising in the context of well defined hereditary syndromes.The pathogenesis of the early-onset disease is substantially well characterized in the inherited subtype,which is mainly associated to the Lynch syndrome and occasionally to other rare mendelian diseases,whereas in the "sporadic" subtype the origin of the disease may be attributed to the presence of various common/rare genetic variants,so far largely unidentified,displaying variable penetrance.These variants are thought to act cumulatively to increase the risk of colorectal cancer,and presumably to also anticipate its onset.Efforts are ongoing in the attempt to unravel the intricate genetic basis of this "sporadic" early-onset disease.A better knowledge of molecular entities and pathways may impact on family-tailored prevention and clinical management strategies.
文摘Colorectal cancer(CRC) is the third most frequent cancer type and the incidence of this disease is increasing gradually per year in individuals younger than 50 years old. The current knowledge is that early-onset CRC(EOCRC) cases are heterogeneous population that includes both hereditary and sporadic forms of the CRC. Although EOCRC cases have some distinguishing clinical and pathological features than elder age CRC, the molecular mechanism underlying the EOCRC is poorly clarified. Given the significance of CRC in the world of medicine, the present review will focus on the recent knowledge in the molecular basis of genetic and epigenetic mechanism of the hereditary forms of EOCRC, which includes Lynch syndrome, Familial CRC type X, Familial adenomatous polyposis, Mut YH-associated polyposis, Juvenile polyposis syndrome, Peutz-Jeghers Syndrome and sporadic forms of EOCRC. Recent findings about molecular genetics and epigenetic basis of EOCRC gave rise to new alternative therapy protocols. Although exact diagnosis of these cases still remains complicated, the present review paves way for better predictions and contributes to more accurate diagnostic and therapeutic strategies into clinical approach.
基金Supported by National Nature Science Foundation of China,No.81400588
文摘AIM: To perform sequencing analysis in patients with very early-onset inflammatory bowel disease(VEO-IBD) to determine the genetic basis for VEO-IBD in Chinese pediatric patients.METHODS: A total of 13 Chinese pediatric patients with VEO-IBD were diagnosed from May 2012 and August 2014. The relevant clinical characteristics of these patients were analyzed. Then DNA in the peripheral blood from patients was extracted. Next generation sequencing(NGS) based on an IlluminaMiseq platform was used to analyze the exons in the coding regions of 10 candidate genes: IL-10, IL-10 RA, IL-10 RB, NOD2, FUT2, IL23 R, GPR35, GPR65, TNFSF15, and ADAM30. The Sanger sequencing was used to verify the variations detected in NGS.RESULTS: Out of the 13 pediatric patients, ten were diagnosed with Crohn's disease, and three diagnosed with ulcerative colitis. Mutations in IL-10 RA and IL-10 RB were detected in five patients. There were four patients who had single nucleotide polymorphisms associated with IBD. Two patients had IL-10 RA andFUT2 polymorphisms, and two patients had IL-10 RB and FUT2 polymorphisms. Gene variations were not found in the rest four patients. Children with mutations had lower percentile body weight(1.0% vs 27.5%, P = 0.002) and hemoglobin(87.4 g/L vs 108.5 g/L, P = 0.040) when compared with children without mutations. Although the age of onset was earlier, height was shorter, and the response to treatment was poorer in the mutation group, there was no significant difference in these factors between groups.CONCLUSION: IL-10 RA and IL-10 RB mutations are common in Chinese children with VEO-IBD. Patients with mutations have an earlier disease onset, lower body weight and hemoglobin, and poorer prognosis.
基金supported by the National Natural Science Foundation of China (grants 30671813,30872178,81072366,and 81273149)Guangdong Provincial High Level Experts Grants (No.2010-79)+1 种基金Changjiang Scholars and Innovative Research Team in University grant (No.IRT0961)Guangdong Natural Science Foundation Team Grant (No.10351012003000000 to Dr.J.Lu)
文摘Essential meiotic endonuclease 1 homolog 1 (EME1) is a key DNA repair protein that participates in the recognition and repair of DNA double-strand breaks. Deficiency of the EME1 gene can lead to spontaneous genomic instability and thus contribute to tumorgenesis. We hypothesized that the exon variants of EME1 confer genetic susceptibility to breast cancer. In a case-control study of 748 breast cancer patients and 778 normal controls, we analyzed the association between two exon variants of EME1 (i.e.,Ile350Thr: rs12450550T>C and Glu69Asp: rs3760413T>G) and breast cancer risk. We found that compared to the common Ile/Ile genotype, the Thr variant genotypes (Thr/Ile+Thr/Thr) conferred a 1.47-fold increased risk of breast cancer (OR=1.47, 95% CI=1.13-1.92). The variant Ile350Thr was also associated with early onset of breast cancer (r=-0.116, P=0.002). The mean age of onset was 44.4 years for Thr/Thr genotype carriers and 46.5 years for Thr/Ile genotype carriers, which was significantly lower than that (49.4 years) for Ile/Ile genotype carriers (P=0.006). Moreover, no significant association was observed between the Glu69Asp variant and breast cancer risk. Our findings suggest that the EME1 variant Ile350Thr contributes to an increased risk and early onset of breast cancer.
文摘There is by no means a clear-cut pattern of mutations contributing to gastric cancers,and gastric cancer research can be hampered by the diversity of factors that can induce gastric cancer,such as Helicobacter pylori infection,diet,ageing and other environmental factors.Tumours are unquestionably riddled with genetic changes yet we are faced with an unsolvable puzzle with respect to a temporal relationship.It is postulated that inherited genetic factors may be more important in early-onset gastric cancer (EOGC) than in gastric cancers found in older patients as they have less exposure to environmental carcinogens.EOGC,therefore,could provide a key to unravelling the genetic changes in gastric carcinogenesis.Gastric cancers occurring in young patients provide an ideal background on which to try and uncover the initiating stages of gastric carcinogenesis.This review summarizes the literature regarding EOGC and also presents evidence that these cancers have a unique molecular-genetic phenotype,distinct from conventional gastric cancer.
基金Supported by Project PI10/0683 from the Spanish Ministry of Health and Consumer Affairs
文摘Colorectal cancer(CRC)has a great impact on the world population.With increasing frequency,CRC is described according to the presenting phenotype,based on its molecular characteristics.Classification of CRC tumors according to their genetic and/or epigenetic alterations is not only important for establishing the molecular bases of the disease,but also for predicting patient outcomes and developing more individualized treatments.Early-onset CRC is a heterogeneous disease,with a strong familial component,although the disease is sporadic in an important proportion of cases.Different molecular alterations appear to contribute to the apparent heterogeneity of the early-onset population and subgroups can be distinguished with distinct histopathologic and familial characteristics.Moreover,compared with late-onset CRC,there are characteristicsthat suggest that early-onset CRC may have a different molecular basis.The purpose of this review was to analyze the current state of knowledge about earlyonset CRC with respect to clinicopathologic,familial and molecular features.Together,these features make it increasingly clear that this subset of CRC may be a separate disease,although it has much in common with late-onset CRC.
文摘BACKGROUND Colorectal cancer(CRC)is the second leading cause of all cancer related deaths in the United States and Europe.Although the incidence has been decreasing for individuals’≥50,it has been on the rise for individuals<50.AIM To identify potential risk factors for early-onset CRC.METHODS A population-based cohort analysis using a national database,Explorys,screened all patients with an active electronic medical record from January 2012 to December 2016 with a diagnosis of CRC.Subgroups were stratified based on age(25–49 years vs≥50 years).Demographics,comorbidities,and symptom profiles were recorded and compared between both age groups.Furthermore,the younger group was also compared with a control group consisting of individuals aged 25-49 years within the same timeframe without a diagnosis of CRC.Twentydata points for CRC related factors were analyzed to identify potential risk factors specific to early-onset CRC.RESULTS A total of 68860 patients were identified with CRC,of which 5710(8.3%)were younger than 50 years old,with 4140(73%)between 40-49 years of age.Multivariable analysis was reported using odds ratio(OR)with 95%CI and demonstrated that several factors were associated with an increased risk of CRC in the early-onset group versus the later-onset group.These factors included:African-American race(OR 1.18,95%CI:1.09-1.27,P<0.001),presenting symptoms of abdominal pain(OR 1.82,95%CI:1.72-1.92,P<0.001),rectal pain(OR 1.50,95%CI:1.28-1.77,P<0.001),altered bowel function(OR 1.12,95%CI:1.05-1.19,P=0.0005),having a family history of any cancer(OR 1.78,95%CI:1.67-1.90,P<0.001),gastrointestinal(GI)malignancy(OR 2.36,95%CI:2.18-2.55,P<0.001),polyps(OR 1.41,95%CI:1.08-1.20,P<0.001),and obesity(OR 1.14,95%CI:1.08-1.20,P<0.001).Comparing the early-onset cohort versus the control group,factors that were associated with an increased risk of CRC were:male gender(OR 1.34,95%CI:1.27-1.41),P<0.001),Caucasian(OR 1.48,95%CI:1.40-1.57,P<0.001)and African-American race(OR 1.25,95%CI:1.17-1.35,P<0.001),presenting symptoms of abdominal pain(OR 4.73,95%CI:4.49-4.98,P<0.001),rectal pain(OR 7.48,95%CI:6.42-8.72,P<0.001),altered bowel function(OR 5.51,95%CI:5.19-5.85,P<0.001),rectal bleeding(OR 9.83,95%CI:9.12-10.6,P<0.001),weight loss(OR 7.43,95%CI:6.77-8.15,P<0.001),having a family history of cancer(OR 11.66,95%CI:10.97-12.39,P<0.001),GI malignancy(OR 28.67,95%CI:26.64-30.86,P<0.001),polyps(OR 8.15,95%CI:6.31-10.52,P<0.001),tobacco use(OR 2.46,95%CI:2.33-2.59,P<0.001),alcohol use(OR 1.71,95%CI:1.62-1.80,P<0.001),presence of colitis(OR 4.10,95%CI:3.79-4.43,P<0.001),and obesity(OR 2.88,95%CI:2.74-3.04,P<0.001).CONCLUSION Pending further investigation,these potential risk factors should lower the threshold of suspicion for early CRC and potentially be used to optimize guidelines for early screening.
基金the National Natural Science Foundation of China,No.30400144
文摘Mutation of the DYT1 gene has been reported to cause early-onset primary torsion dystonia (DYT1).Due to DYT1 gene mutation,defective wild torsinA and the accumulation of mutant torsinA (GAG-deleted DYT1 gene encoded the mutant torsinA,torsinA?E) play an important role in DYT1 pathogenesis.Intracellular inclusion bodies are formed,and dopamine transport and release are disturbed by interfering functions of endoplasmic reticulum,nuclear membrane,and cytoskeleton of neural cells,resulting in DYT1 onset.Small interfering RNA could serve as a potential therapy for DYT1.However,the exact function of wild torsinA and the pathological effects of torsinA?E require further studies.
基金Supported by A grant from the Polish Ministry of Science and Higher EducationNo.N N402 423838
文摘Currently, gastric cancer(GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the procarcinogenic activity of important genes. These factors include genetic susceptibility expressed in a singlenucleotide polymorphism, various acquired mutations(chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances(e.g., helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma(EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesisare modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC.
