Global increase of colorectal cancer in young adults over the last 30 years: an analysis of the Global Burden of Disease Study 2019.

OBJECTIVES: The US Preventive Services Task Force lowered the recommended starting age for colorectal cancer (CRC) screening in average-risk adults from 50 to 45 years. We aimed to estimate the global burden and trends of colorectal cancer in adults aged 20-49 years (early-onset CRC). METHODS: This is an analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019). The GBD 2019 estimation methods were used to describe the incidence, mortality, and disability-adjusted life years (DALYs) of early CRC from 1990 to 2019. Data from 204 countries and geographic areas were available. RESULTS: The global incidence rate of early-onset CRC increased from 4.2/100 000 to 6.7/100 000 from 1990 to 2019. Mortality and DALYs of early-onset CRC also increased. The CRC incidence rate increased faster in younger adults (1.6%) than in adults aged 50-74 years (0.6%) as measured by the annual percentage change. The increase in early-onset CRC incidence was consistently observed in all five socio-demographic index (SDI) regions and 190 out of 204 countries and territories. Middle and high-middle SDI regions had faster annual increases in early-onset CRC, which warrants further attention. CONCLUSIONS: The global incidence, mortality, and DALYs of early-onset CRC increased from 1990 to 2019. The increase in early-onset CRC incidence was prevalent worldwide. Several countries were found to have higher incidence rates than the United States or fast increase in early-onset CRC, which warrants further attention.

Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study.

Background: There is an increased trend of e-cigarette but the toxic effects of e-cigarette metabolites are not widely studied especially in liver disease. Hence, we aimed to evaluate the prevalence and patterns of recent e-cigarette use in a nationally representative sample of US adults and adolescents and its association amongst respondents with liver disease. Methods: We conducted a retrospective cross-sectional study using National Health and Nutrition Examination Survey (NHANES) database from 2015 to 2018. The self-reported NHANES questionnaire was used to assess liver disease (MCQ160L, MCQ170L and MCQ 510 (a-e)), e-cigarette use (SMQ900) and traditional smoking status (SMQ020 or SMQ040). We conducted univariate analysis and multivariable logistic regression models to predict the association of e-cigarette use, traditional smoking and dual smoking amongst the population with liver disease. Results: Out of total 178,300 respondents, 7,756 (4.35%) were e-cigarette users, 48,625 (27.27%) traditional smoking, 23,444 (13.15%) dual smoking and 98,475 (55.23%) non-smokers. Females had a higher frequency of e-cigarette use (49.3%) compared to dual (43%) and traditional smoking (40.8%) (P < 0.0001). Respondents with a past history of any liver disease have lower frequency of e-cigarette use compared to dual and traditional smoking, respectively (2.4% vs. 6.4% vs. 7.2%; P < 0.0001). In multivariate logistic regression models, we found that e-cigarette users (odds ratio (OR): 1.06; 95% confidence interval (CI): 1.05 - 1.06; P < 0.0001) and dual smoking (OR: 1.50; 95% CI: 1.50 - 1.51; P < 0.0001) were associated with higher odds of having history of liver disease compared to non-smokers. Conclusion: Our study found that despite the low frequency of e-cigarette use in respondents with liver disease, there was higher odds of e-cigarette use amongst patients with liver disease. This warrants the need for more future prospective studies to evaluate the long-term effects and precise mechanisms of e-cigarette toxicants on the liver.

Neonatal outcome of extremely preterm Asian infants ⩽28 weeks over a decade in the new millennium.

OBJECTIVE: To evaluate predischarge neonatal mortality and morbidity and associated risk factors in extremely preterm Asian infants ⩽28 weeks, over a decade, so as to facilitate formulation of perinatal guidelines and counseling. STUDY DESIGN: Cohort study of 887 liveborn extremely preterm neonates between 2000 and 2009 at KKH, the centralized perinatal center in Singapore. Outcome measures were predischarge mortality, presence of one or more major neonatal morbidities and the composite outcome of mortality or neonatal morbidity. RESULT: Overall survival to discharge was 709/887 (80%) and was significantly higher with increasing gestational age (GA) (19% at 23 weeks to 93% at 28 weeks, P<0.001). Survival remained unchanged between 78 and 86% during the decade with no significant secular trend. Overall incidence of major morbidities were bronchopulmonary dysplasia (29%), late onset sepsis (23%), severe retinopathy of prematurity (21%), Grade 3 to 4 intraventricular hemorrhage (12%) and necrotizing enterocolitis ⩾Bells' stage II/focal intestinal perforation (9%). Composite morbidity was seen in 465/835 (56%) neonatal intensive-care unit admissions, decreased with increasing GA (P<0.001; odds ratio 0.65 (95% confidence interval 0.56 to 0.75) and was independently predicted by birth weight, Clinical Risk Index for Babies-revised version II score, male gender, presence of patent ductus arteriosus and airleaks. CONCLUSION: Although there was no significant trend in neonatal survival or composite morbidity over the decade, improved survival and morbidity were seen with increasing GA.

Neonatal hepatic abscess in preterm infants:a rare entity?

INTRODUCTION AND OBJECTIVE: Neonatal pyogenic hepatic abscess in preterm infants is a rare entity. We present 6 cases of neonatal liver abscesses diagnosed in our hospital as well as an approach that will facilitate the early diagnosis and management of neonatal pyogenic liver abscess based on our case series and review of the literature. MATERIALS AND METHODS: Retrospective review of case records of all 6 patients diagnosed with neonatal liver abscess from January 2000 to December 2002 in KK Women's and Children's Hospital, Singapore. RESULTS: All neonates were premature with gestational ages between 24 and 34 weeks. Persistence of positive blood culture despite appropriate antibiotic treatment in 67% of the cases prompted use of hepatobiliary ultrasounds to detect liver abscess. Surgical drainage of liver abscess was performed in 33% of the cases, with the remainder treated conservatively with appropriate intravenous antibiotics. Half of the infants recovered with resolution of their liver abscess on serial hepatobiliary ultrasound. The other half died of fulminant sepsis. CONCLUSIONS: Neonatal pyogenic liver abscess, though rare, is associated with good outcome if diagnosed promptly and appropriate treatment instituted. In a preterm infant with sepsis, a high index of suspicion is required if there is persistence of positive blood culture despite appropriate antibiotic treatment, and hepatobiliary ultrasound should be done to detect and monitor neonatal liver abscess.

Immunogenicity and reactogenicity of two regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio and Haemophilus influenzae type b vaccines administered to infants primed at birth with hepatitis B vaccine.

An open, randomized study evaluated the immune response and safety of two different regimens of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b (DTPa-HBV-IPV-Hib) immunization in infants primed at birth with hepatitis B vaccine. One-half of the 150 healthy, full-term infants received a DTPa HBV-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age; the other received a DTPa-IPV-Hib vaccine at 1 1/2, 3 and 5 months of age with separate HBV vaccine at 1 and 5 months of age. Immune response was similar following the two regimens with 100% of the vaccinees seroprotected for HBV, diphtheria, tetanus, Hib and poliovirus types 2 and 3 diseases after the full vaccination course. One vaccinee in the DTPa HBV-HPV- Hib group failed to respond to the poliovirus type 1 antigen. Response to the three pertussis antigens ranged from 92-97% in the DTPa-IPV-Hib plus separate HBV group and 100% in the DTPa HBV-IPV-Hib group. The most frequently reported post-vaccination symptoms were irritability in the DTPa-IPV-Hib plus separate HBV group (49% of vaccinees) and fever, defined as axillary temperature > or =37.5 degrees C, in the DTPa HBV- IPV-Hib group (50% of vaccinees).

In vitro-selected RNA cleaving DNA enzymes from a combinatorial library are potent inhibitors of HIV-1 gene expression.

Selective inactivation of a target gene by antisense mechanisms is an important biological tool to delineate specific functions of the gene product. Approaches mediated by ribozymes and RNA-cleaving DNA enzymes (DNA enzymes) are more attractive because of their ability to catalytically cleave the target RNA. DNA enzymes have recently gained a lot of importance because they are short DNA molecules with simple structures that are expected to be stable to the nucleases present inside a mammalian cell. We have designed a strategy to identify accessible cleavage sites in HIV-1 gag RNA from a pool of random DNA enzymes, and for isolation of DNA enzymes. A pool of random sequences (all 29 nucleotides long) that contained the earlier-identified 10-23 catalytic motif were tested for their ability to cleave the target RNA. When the pool of random DNA enzymes was targeted to cleave between any A and U nucleotides, DNA enzyme 1836 was identified. Although several DNA enzymes were identified using a pool of DNA enzymes that was completely randomized with respect to its substrate-binding properties, DNA enzyme-1810 was selected for further characterization. Both DNA enzymes showed target-specific cleavage activities in the presence of Mg(2+) only. When introduced into a mammalian cell, they showed interference with HIV-1-specific gene expression. This strategy could be applied for the selection of desired target sites in any target RNA.

Targeted cleavage of HIV-1 coreceptor-CXCR-4 by RNA-cleaving DNA-enzyme: inhibition of coreceptor function.

HIV needs the chemokine receptors (HIV-1 coreceptors) to initiate infection and gain entry into a susceptible cell. CCR5 receptor is used by macrophage tropic viruses to establish infection, and CXCR-4 is used by T lymphocyte tropic virus which are usually found at the terminal stages of the disease. These chemokine receptors are, therefore, attractive targets to interfere with the entry as well as spread of HIV-1 in the host. As our antiviral approach, we have earlier assembled a DNA-enzyme-916 against CCR5 (Goila and Banerjea, 1998). We have now designed against the CXCR-4 gene a mono-DNA-enzyme, which showed sequence specific cleavage activity. When CXCR-4-DNA-enzyme was placed in tandem with CCR5-DNA-enzyme, specific cleavage of their respective target sites were observed using a 60 bases long synthetic target RNA which possessed the target sites for both the DNA-enzymes. The cleavage by the CXCR-4 DNA-enzyme was found to be significantly more efficient than by the CCR5-DNA-enzyme. Analyses of the cleaved fragments by mono- and di-DNA-enzyme indicated strongly that hybridization of the CCR5-DNA-enzyme with its cognate target RNA, actually facilitated the cleavage by the CXCR-4 DNA-enzyme. Furthermore, the di-DNA-enzyme was able to cleave the substrate RNA to completion. These DNA-enzymes, when introduced into a mammalian cell line expressing the appropriate chemokine receptor, interfered specifically with the HIV-1 coreceptor functions. Using this strategy, it may be possible to interfere with the infection and spread of R5 as well as X4 viruses.