Updates in the field of hereditary nonpolyposis colorectal cancer : Expert Review of Gastroenterology & Hepatology

ABSTRACT Introduction Up to one third of colorectal cancers show familial clustering and 5% are hereditary single-gene disorders. Hereditary non-polyposis colorectal cancer comprises DNA mismatch repair-deficient and -proficient subsets, represented by Lynch syndrome (LS) and familial colorectal cancer type X (FCCTX), respectively. Accurate knowledge of molecular etiology and genotype-phenotype correlations are critical for tailored cancer prevention and treatment. Areas covered The authors highlight advances in the molecular dissection of hereditary non-polyposis colorectal cancer, based on recent literature retrieved from PubMed. Future possibilities for novel gene discoveries are discussed. Expert commentary LS is molecularly well established, but new information is accumulating of the associated clinical and tumor phenotypes. FCCTX remains poorly defined, but several promising candidate genes have been discovered and share some preferential biological pathways. Multi-level characterization of specimens from large patient cohorts representing multiple populations, combined with proper bioinformatic and functional analyses, will be necessary to resolve the outstanding questions.Peer reviewe

Serum transglutaminase 3 antibodies correlate with age at celiac disease diagnosis

Background: Transglutaminase (TG)2 is the autoantigen in celiac disease, but also TG3 antibodies have been detected in the serum of celiac disease patients. Aims: To investigate the correlations between serum TG3 antibodies and clinical and histological manifestations of celiac disease and to assess gluten-dependency of TG3 antibodies. Methods: Correlations between serum TG3 antibody levels measured from 119 adults and children with untreated coeliac disease and the demographic data, clinical symptoms, celiac antibodies, histological data and results of laboratory tests and bone mineral densities were tested. TG3 antibodies were reinvestigated in 97 celiac disease patients after 12 months on a gluten-free diet (GFD). Results: TG3 antibody titers were shown to correlate with the age at celiac disease diagnosis. Further, negative correlation with TG3 antibodies and intestinal gamma delta+ cells at diagnosis and on GFD was detected. Correlations were not detected with the clinical manifestation of celiac disease, TG2 or endomysial autoantibodies, laboratory values, severity of mucosal villous atrophy, associated diseases or complications. TG3 antibody titers decreased on GFD in 56% of the TG3 antibody positive patients. Conclusion: Serum TG3 antibody positivity in celiac disease increases as the diagnostic age rises. TG3 antibodies did not show similar gluten-dependency as TG2 antibodies. (C) 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Prognosis of patients with operated chronic subdural hematoma

Chronic subdural hematoma (cSDH), previously considered fairly benign and easy to treat, is now viewed a possible sign of incipient clinical decline. We investigated case-fatality, excess fatality and need for reoperations following operated cSDH in a nationwide setting focusing on patient-related characteristics. Finnish nationwide databases were searched for all admissions with operated cSDH as well as later deaths in adults (>= 16 years) during 2004-2017. There were 8539 patients with an evacuated cSDH (68% men) with a mean age of 73.0 (+/- 12.8) years. During the follow-up, 3805 (45%) patients died. In-hospital case-fatality was 0.7% (n = 60) and 30-day case-fatality 4.2% (n = 358). The 1-year case-fatality was 14.3% (95% CI = 13.4-15.2%) among men and 15.3% (95% CI = 14.0-16.7%) among women. Comorbidity burden, older age, and alcoholism were significantly associated with fatality. One-year excess fatality rate compared to general Finnish population was 9.1% (95% CI = 8.4-9.9) among men and 10.3% (95% CI = 9.1-11.4) among women. Highest excess fatality was observed in the oldest age group in both genders. Reoperation was needed in 19.4% (n = 1588) of patients. Older age but not comorbidity burden or other patient-related characteristics were associated with increased risk for reoperation. The overall case-fatality and need for reoperations declined during the study era. Comorbidities should be considered when care and follow-up are planned in patients with cSDH. Our findings underpin the perception that the disease is more dangerous than previously thought and causes mortality in all exposed age groups: even a minor burden of comorbidities can be fatal in the post-operative period

Students\u2019 experiences of cooperation with nurse teacher during their clinical placements: an empirical study in a Western European context.

In many European countries during the last decade, the clinical role of the nurse teacher has changed from a clinical skilled practitioner to a liaison person working between educational and health care provider organisations. This study explored pre-registration nursing students' perceptions of cooperation with nurse teachers during their clinical placements in nine Western European countries. The study also assessed the type and range of e-communication between students and nurse teachers and whom the students\u2019 perceived as their most important professional role model. The study is a descriptive survey. Quantitative data were collected from 17 higher education institutes of nursing located in the northern, middle and southern parts of Europe. The purposive sample (N=1903) comprised students who had participated in courses which included clinical placements. The data were analysed using descriptive statistics. Comparisons between the groups were made using cross-tabulation. The majority (57%) of students met their nurse teacher 1-3 times during their placement while 13% of the students did not meet their nurse teacher at all. Additionally, 66% of respondents used some form of e-communication (e-mail, mobile text messages etc.) to communicate with their nurse teacher. It is important to clarify the division of labour between nurse teachers and Mentors. There are both opportunities and challenges in how to utilise information technology to more effectively promote cooperation between students and nurse teachers

Multiquasiparticle states in the neutron-rich nucleus 174 Tm

Deep inelastic and transfer reactions with an 820-MeV, 136Xe beam and various ytterbium and lutetium targets have been employed to study high-spin structures in the neutron-rich thulium isotopes beyond 171Tm. Results in the doubly odd nucleus, 174Tm, inc

High-spin structure, K isomers, and state mixing in the neutron-rich isotopes 173 Tm and 175 Tm

High-spin states in the odd-proton thulium isotopes 173Tm and 175Tm have been studied using deep-inelastic reactions and γ-ray spectroscopy. In 173Tm, the low-lying structure has been confirmed and numerous new states have been identified, including a t

Ideal cardiovascular health in childhood-Longitudinal associations with cardiac structure and function : The Special Turku Coronary Risk Factor Intervention Project (STRIP) and the Cardiovascular Risk in Young Finns Study (YFS)

Background: Ideal cardiovascular health (CVH), defined by the American Heart Association, is associated with incident cardiovascular disease in adults. However, association of the ideal CVH in childhood with current and future cardiac structure and function has not been studied. Methods and results: The sample comprised 827 children participating in the longitudinal Special Turku Coronary Risk Factor Intervention Project (STRIP) and The Cardiovascular Risk in Young Finns Study (YFS). In STRIP, complete data on the seven ideal CVH metrics and left ventricular (LV) mass measured with echocardiography were available at the age of 15 (n= 321), 17 (n= 309) and 19 (n= 283) years. In YFS, the cohort comprised children aged 12-18 years (n = 506) with complete ideal CVH metrics data from childhood and 25 years later in adulthood, and echocardiography performed in adulthood. In STRIP, ideal CVH score was inversely associated with LV mass during childhood (P = 0.036). In YFS, childhood ideal CVH score was inversely associated with LV mass, LV end-diastolic volume, E/e' ratio, and left atrium end-systolic volume in adulthood (all P <0.01). In addition, improvement of the ideal CVH score between childhood and adulthood was inversely associated with LV mass, LV end-diastolic volume, E/e' ratio, and left atrium end-systolic volume (all P Conclusions: Childhood ideal CVH score has a long-lasting effect on cardiac structure and function, and the association is evident already in childhood. Our findings support targeting the ideal CVHmetrics as part of primordial prevention of cardiovascular diseases. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Peer reviewe

Urinary Biomarkers Indicative of Apoptosis and Acute Kidney Injury in the Critically Ill

Background Apoptosis is a key mechanism involved in ischemic acute kidney injury (AKI), but its role in septic AKI is controversial. Biomarkers indicative of apoptosis could potentially detect developing AKI prior to its clinical diagnosis. Methods As a part of the multicenter, observational FINNAKI study, we performed a pilot study among critically ill patients who developed AKI (n = 30) matched to critically ill patients without AKI (n = 30). We explored the urine and plasma levels of cytokeratin-18 neoepitope M30 (CK-18 M30), cell-free DNA, and heat shock protein 70 (HSP70) at intensive care unit (ICU) admission and 24h thereafter, before the clinical diagnosis of AKI defined by the Kidney Disease: Improving Global Outcomes - creatinine and urine output criteria. Furthermore, we performed a validation study in 197 consecutive patients in the FINNAKI cohort and analyzed the urine sample at ICU admission for CK-18 M30 levels. Results In the pilot study, the urine or plasma levels of measured biomarkers at ICU admission, at 24h, or their maximum value did not differ significantly between AKI and non-AKI patients. Among 20 AKI patients without severe sepsis, the urine CK-18 M30 levels were significantly higher at 24h (median 116.0, IQR [32.3-233.0] U/L) than among those 20 patients who did not develop AKI (46.0 [0.0-54.0] U/L), P = 0.020. Neither urine cell-free DNA nor HSP70 levels significantly differed between AKI and non-AKI patients regardless of the presence of severe sepsis. In the validation study, urine CK-18 M30 level at ICU admission was not significantly higher among patients developing AKI compared to non-AKI patients regardless of the presence of severe sepsis or CKD. Conclusions Our findings do not support that apoptosis detected with CK-18 M30 level would be useful in assessing the development of AKI in the critically ill. Urine HSP or cell-free DNA levels did not differ between AKI and non-AKI patients.Peer reviewe

Germline Mutation of RPS20, Encoding a Ribosomal Protein, Causes Predisposition to Hereditary Nonpolyposis Colorectal Carcinoma Without DNA Mismatch Repair Deficiency

Peer reviewe

Childhood predictors of adult fatty liver. The Cardiovascular Risk in Young Finns Study

Background & Aims: Fatty liver is a potentially preventable cause of serious liver diseases. This longitudinal study aimed to identify childhood risk factors of fatty liver in adulthood in a population-based group of Finnish adults. Methods: Study cohort included 2,042 individuals from the Cardiovascular Risk in Young Finns Study aged 3-18 years at baseline in 1980. During the latest follow-up in 2011, the liver was scanned by ultrasound. In addition to physical and environmental factors related to fatty liver, we examined whether the genetic risk posed by a single nucleotide polymorphism in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) (rs738409) strengthens prediction of adult fatty liver. Results: Independent childhood predictors of adult fatty liver were small for gestational age, (odds ratio = 1.71, 95% confidence interval = 1.07-2.72), variant in PNPLA3 (1.63, 1.29-2.07 per one risk allele), variant in the transmembrane 6 superfamily 2 gene (TM6SF2) (1.57, 1.08-2.30), BMI (1.30, 1.07-1.59 per standard deviation) and insulin (1.25, 1.05-1.49 per standard deviation). Childhood blood pressure, physical activity, C-reactive protein, smoking, serum lipid levels or parental lifestyle factors did not predict fatty liver. Risk assessment based on childhood age, sex, BMI, insulin levels, birth weight, TM6SF2 and PNPLA3 was superior in predicting fatty liver compared with the approach using only age, sex, BMI and insulin levels (C statistics, 0.725 vs. 0.749; p = 0.002). Conclusions: Childhood risk factors on the development of fatty liver were small for gestational age, high insulin and high BMI. Prediction of adult fatty liver was enhanced by taking into account genetic variants in PNPLA3 and TM6SF2 genes. Lay summary: The increase in pediatric obesity emphasizes the importance of identification of children and adolescents at high risk of fatty liver in adulthood. We used data from the longitudinal Cardiovascular Risk in Young Finns Study to examine the associations of childhood (3-18 years) risk variables with fatty liver assessed in adulthood at the age of 34-49 years. The findings suggest that a multifactorial approach with both lifestyle and genetic factors included would improve early identification of children with a high risk of adult fatty liver. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.Peer reviewe