A systematic review on the existing screening pathways for Lynch syndrome identification

Background: Lynch syndrome (LS) is the most common hereditary colon cancer syndrome, accounting for 3-5% of colorectal cancer (CRC) cases, and it is associated with the development of other cancers. Early detection of individuals with LS is relevant, since they can take advantage of life-saving intensive care surveillance. The debate regarding the best screening policy, however, is far from being concluded. This prompted us to conduct a systematic review of the existing screening pathways for LS. Methods: We performed a systematic search of MEDLINE, ISI Web of Science, and SCOPUS online databases for the existing screening pathways for LS. The eligibility criteria for inclusion in this review required that the studies evaluated a structured and permanent screening pathway for the identification of LS carriers. The effectiveness of the pathways was analyzed in terms of LS detection rate. Results: We identified five eligible studies. All the LS screening pathways started from CRC cases, of which three followed a universal screening approach. Concerning the laboratory procedures, the pathways used immunohistochemistry and/or microsatellite instability testing. If the responses of the tests indicated a risk for LS, the genetic counseling, performed by a geneticist or a genetic counselor, was mandatory to undergo DNA genetic testing. The overall LS detection rate ranged from 0 to 5.2%. Conclusion: This systematic review reported different existing pathways for the identification of LS patients. Although current clinical guidelines suggest to test all the CRC cases to identify LS cases, the actual implementation of pathways for LS identification has not been realized. Large-scale screening programs for LS have the potential to reduce morbidity and mortality for CRC, but coordinated efforts in educating all key stakeholders and addressing public needs are still required

Developmental language disorder: Early predictors, age for the diagnosis, and diagnostic tools. A scoping review

Background. Developmental Language Disorder (DLD) is frequent in childhood and may have long-term sequelae. By employing an evidence-based approach, this scoping review aims at identifying (a) early predictors of DLD; (b) the optimal age range for the use of screening and diagnostic tools; (c) effective diagnostic tools in preschool children. Methods. We considered systematic reviews, meta-analyses, and primary observational studies with control groups on predictive, sensitivity and specificity values of screening and diagnostic tools and psycholinguistic measures for the assessment of DLD in preschool children. We identified 37 studies, consisting of 10 systematic reviews and 27 primary studies. Results. Delay in gesture production, receptive and/or expressive vocabulary, syntactic comprehension, or word combination up to 30 months emerged as early predictors of DLD, a family history of DLD appeared to be a major risk factor, and low socioeconomic status and environmental input were reported as risk factors with lower predictive power. Optimal time for screening is suggested between age 2 and 3, for diagnosis around age 4. Because of the high variability of sensitivity and specificity values, joint use of standardized and psycholinguistic measures is suggested to increase diagnostic accuracy. Conclusions. Monitoring risk situations and employing caregivers\u2019 reports, clinical assessment and multiple linguistic measures are fundamental for an early identification of DLD and timely interventions

Intervals for the new Brahms Chromogranin A (CGA) assay

neuroendocrine tumours. To improve analytical performance and decrease test turnaround time, we introduced the new fully automated Brahms CGA assay performed on Kryptor platform. As CGA results from different assays are not comparable, we performed a study for establishing reference intervals for the new assay. Methods: Fresh serum samples were obtained from 200 healthy blood donors and immediately measured for CGA. Shapiro-Wilk and Wilcoxon rank sum tests were employed to assess distribution of CGA values and compare groups, respectively. Multiple regression models were used to evaluate the influence of age and sex on CGA concentrations, including the interaction between the two factors. Results: 4 elevated CGA values were statistical outliers and in 3 of those individuals an interfering condition possibly increasing CGA was identified (hyperthyroidism, vitamin D supplementation, use of hormonal contraceptives). After their exclusion the remaining values from 196 subjects [99 males and 97 females; median age (range) 44 years (19-67)] were analyzed. Median (range) CGA concentration was 41.6 \u3bcg/L (15.9-146.2), with no gender-related difference. Although deviating from normal frequency distribution, the visual examination of data did not suggest log transformation. Regression analysis confirmed the lack of gender influence, showing however that CGA concentrations increased with age (P <0.001). The lack of biological interaction between age and sex excluded the hypothesis that menopausal status may influence CGA release. Aiming to decide if reference values should be partitioned by age, we compared CGA concentrations in subjects <45 (n=99) and 6545 years (n=97). Higher CGA concentrations were found in older people (mean\ub1SD: 49.1\ub118.6 \u3bcg/L vs. 41.8\ub119.4 \u3bcg/L, P=0.0006). Accounting for manufacturer\u2019s declared imprecision at CGA range of 80-120 \u3bcg/L (CV <7%) and the estimated upper reference limit (97.5th percentile - URL) for subjects 6545 (98.5 \u3bcg/L) and <45 (87.0 \u3bcg/L), we however decided to adopt a single URL for overall population (93.7 \u3bcg/L; 90%CI: 79.0- 114.1). Conclusions: In healthy subjects age but not gender may affect CGA release. However this does not appear to require agerelated reference limits