Longitudinal Doppler references for monochorionic twins and comparison with singletons

OBJECTIVES: To construct monochorionic (MC) twin-specific longitudinal Doppler references for umbilical artery pulsatility index (UA-PI), middle cerebral artery (MCA) PI and peak systolic velocity (PSV) and ductus venosus (DV) PI derived from a strictly selected cohort of uncomplicated MC twins. The secondary aim of the study was to compare our findings with singleton reference charts. METHODS: A retrospective evaluation was made of all consecutive uncomplicated MC twin pregnancies referred to our Unit from 2010 to 2018. Fortnightly serial examinations were performed of UA-PI, MCA-PI, MCA-PSV and DV-PI, according with the clinical protocol, from 20 to 37 weeks of gestation. We included cases with at least four ultrasound examinations, delivery at our hospital and complete neonatal follow up. A two-step method was used to trace the estimated centile curves: estimation of the median was performed with appropriate fractional polynomials by a multilevel model and estimation of the external centiles through the residuals (quantile regression). The comparison with singletons was made by plotting the references derived from the present study on the referred charts commonly used for singletons. RESULTS: The study group comprised 150 uncomplicated MC twin pairs. Estimated centiles (3rd, 5th, 10th, 50th, 90th, 95th, 97th) of UA-PI, MCA-PI, MCA-PSV and DV-PI in function of the gestational age are presented. The comparison with singletons showed substantial differences, with higher UA-PI and lower MCA-PI and PSV median values in MC twins. Median DV PI values were similar to the values for singletons, while the upper centiles were higher in MC twins. CONCLUSIONS: This study sets out MC twin-specific longitudinal references for UA-PI, MCA-PI, MCA-PSV and DV-PI derived from the largest series of uncomplicated MC twin pregnancies presently available. The comparison with singleton reference values underscores the deviation from physiology that is intrinsic to these unique pregnancies and supports the need for MC twin-specific charts

Urban Ecosystem accounts following the SEEA EA standard: A pilot application in Europe

National and local authorities are promoting restoration actions in urban areas to mitigate societal challenges such as urban heat island, poor air quality or biodiversity loss. Urban re-greening is among the implementation actions supporting targets of the European Green Deal, EU Biodiversity Strategy 2030, its proposal for a Nature Restoration Law, and the proposal for an amendment of the Regulation on Environmental Accounts. However, to monitor progress towards policy targets and an overall enhancement of urban ecosystems, policy makers require regular, consistent and comparable data. The implementation of United Nation's System of Environmental Economic Accounting - Ecosystem Accounting (SEEA EA) on urban ecosystems could help to track changes in their ecosystem extent, condition, services and derived benefits. Despite SEEA EA became a statistical standard, it has been only tested in pilot exercises, of which very few are urban ecosystem accounts. This report presents a pilot SEEA EA urban ecosystem account for EU-27 and EFTA Member States in 2018. It discusses challenges for the development of urban ecosystem accounts and potential solutions. The outputs illustrate where re-greening efforts should be applied and discusses feasibility and potential issues of targets. The report also presents key insights to operationalise SEEA EA for urban ecosystem accounts. It provides an instructive guiding example to national and local authorities starting to draft their own urban ecosystem accounts

Verbal task and motor responses (VTMR) in an adult hearing screening programme

The aim of this study was to test the efficacy of Verbal Tasks and Motor Responses (VTMR) speech audiometry in providing a rapid and true-to-life assessment of hearing-related problems as a single test in adult hearing screening programmes. The VTMR consists in manual execution of 5 verbal commands received by patients at different signal intensity levels and fixed masking noise; it provides a score of speech comprehension in noise. This was a prospective observational study in 916 individuals out of 1,300 volunteers (605 males, 695 females, aged 56 \ub1 17 years) who completed adult hearing screening. VTMR speech audiometry was performed at signal to noise (S/N) ratios of 0 dB and \u201310 dB. The difference between normal and hearing impaired subjects in terms of all the considered variables was statistically significant for pure-tone audiometry and VTMR testing. VTMR testing at a S/N ratio of \u201310 dB with a cut-off of four correctly executed tasks and was a rapid, feasible and efficient means of differentiating between normal and hearing impaired subjects. When used to screen hearing impaired subjects with participation restrictions, the sensitivity and specificity of the VTMR test rose to 90% and 62%, respectively. The VTMR test in noise could be used as a stand-alone tool when screening for impairment and self-perceived participation restriction together

Reproducibility of the WHO histological criteria for the diagnosis of Philadelphia chromosome-negative myeloproliferative neoplasms.

This study, performed on behalf of the Italian Registry of Thrombocythaemias (Registro Italiano Trombocitemie), aimed to test the inter-observer reproducibility of the histological parameters proposed by the WHO classification for the diagnosis of the Philadelphia chromosome-negative myeloproliferative neoplasms. A series of 103 bone marrow biopsy samples of Philadelphia chromosome-negative myeloproliferative neoplasms consecutively collected in 2004 were classified according to the WHO criteria as follows: essential thrombocythaemia (n=34), primary myelofibrosis (n=44) and polycythaemia vera (n=25). Two independent groups of pathologists reviewed the bone marrow biopsies. The first group was asked to reach a collegial 'consensus' diagnosis. The second group reviewed individually all the cases to recognize the main morphological parameters indicated by the WHO classification and report their results in a database. They were subsequently instructed to individually build a 'personal' diagnosis of myeloproliferative neoplasms subtype just assembling the parameters collected in the database. Our results indicate that high levels of agreement ( 6570%) have been reached for about all of the morphological features. Moreover, among the 18 evaluated histological features, 11 resulted statistically more useful for the differential diagnosis among the different Philadelphia chromosome-negative myeloproliferative neoplasms. Finally, we found a high percentage of agreement (76%) between the 'personal' and 'consensus' diagnosis (Cohen's kappa statistic >0.40). In conclusion, our results support the use of the histological criteria proposed by the WHO classification for the Philadelphia chromosome-negative myeloproliferative neoplasms to ensure a more precise and early diagnosis for these patients

Pemetrexed plus carboplatin in elderly patients with malignant pleural mesothelioma: combined analysis of two phase II trials

The incidence of malignant pleural mesothelioma (MPM) in elderly patients is increasing. In this study, pooled data from two phase II trials of pemetrexed and carboplatin (PC) as first-line therapy were retrospectively analysed for comparisons between age groups. Patients received pemetrexed 500 mg m−2 and carboplatin AUC 5 mg ml−1 min−1 intravenously every 21 days with standard vitamin supplementation. Elderly patients were defined as those ⩾70 years old. A total of 178 patients with an ECOG performance status of ⩽2 were included. Median age was 65 years (range 38–79), with 48 patients ⩾70 years (27%). Grade 3–4 haematological toxicity was slightly worse in ⩾70 vs <70-year-old patients, with neutropenia observed in 25.0 vs 13.8% (P=0.11), anaemia in 20.8 vs 6.9% (P=0.01) and thrombocytopenia in 14.6 vs 8.5% (P=0.26). Non-haematological toxicity was mild and similar in the two groups. No significant difference was observed in terms of overall disease control (60.4 vs 66.9%, P=0.47), time to progression (7.2 vs 7.5 months, P=0.42) and survival (10.7 vs 13.9 months, P=0.12). Apart from slightly worse haematological toxicity, there was no significant difference in outcome or toxicity between age groups. The PC regimen is effective and well tolerated in selected elderly patients with MPM

Determining the reference range of blood presepsin in term and preterm neonates

Introduction Sepsis is still a major cause of morbidity and mortality in neonates, especially in preterm infants. Mortality can reach 60-70% in very low birth weight infants (birthweight 0.20). This reduced model explains 3.8% of the total sum of squares. After adjustment for all the factors in the model, presepsin levels appear to be significantly lower in twins (496 pg/ml \uf0b1 65.5 vs 655 pg/ml \uf0b1 11.8) and in neonates with Apgar at 1 min 658 (644 pg/ml \uf0b1 11.8 vs 774 pg/ml \uf0b1 56.2). So none of the above factors seems worth to be taken into account in determining the reference limits for presepsin blood levels in healthy term neonates. Preterm neonates. The largest differences in presepsin level are observed between small for gestational age (SGA) (903 pg/ml \uf0b1 57.1) and adequate for gestational age (AGA) neonates (703 pg/ml \uf0b1 26.7), between neonates with and without mechanical ventilation at blood sampling (1090 pg/ml \uf0b1 86.9 vs 711 pg/ml \uf0b1 24.7) and at delivery (855 pg/ml \uf0b1 87.3 vs 729 pg/ml \uf0b1 25.8), between neonates with and without venous catether (801 pg/ml \uf0b1 47.5 vs 716 pg/ml \uf0b1 28.9), between neonates who underwent blood sampling after the 4th day or before (797 pg/ml \uf0b1 46.2 vs 716 pg/ml \uf0b1 29.2), between males and females (778 pg/ml \uf0b1 35.1 vs 701 pg/ml \uf0b1 34.7). All these factors, when simultaneously introduced into a multivariable linear model, explain only 18.8% of the total sum of squares. A second multivariable linear model was fitted after removing the factors that showed the lowest effect on presepsin level (those associated with a p-value >0.50). This reduced model explains 13.4% of the total sum of squares. A third and more parsimonious multivariable linear model was fitted after removing the factors that showed the lowest effect on presepsin level (those associated with a p-value >0.20). This reduced model explains 12.3% of the total sum of squares. After adjustment for all the factors in the model, presepsin levels result to be significantly lower in AGA neonates (706 pg/ml \uf0b1 25.7 vs 890 pg/ml \uf0b1 55.0) and between neonates with and without mechanical ventilation at blood sampling (1074 pg/ml \uf0b1 85.3 vs 712 pg/ml \uf0b1 24.2). Even in this case, none of the above factors is expected to substantially affect the reference limits for presepsin blood levels in preterm neonates. Conclusion Presepsin blood levels seem to be quite independent of most of maternal and neonatal conditions examined in this study both in preterm and term neonates. The factors exerting significant effects (multiple birth and Apgar at 1 min, in term neonates, weight by gestational age and mechanical ventilation in preterm neonates) are expected to affect presepsin reference limits only to minor extent. References [1] Evaluation of a newly identified soluble CD14 subtype as a marker for sepsis. Yaegashi Y., Shirakawa K., Sato N., Suzuki Y., Kojika M., Imai S., Takahashi G., Miyata M., Furusako S., Endo S. J Infect Chemother. 2005;11:234-8. [2] CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infection in the acute care setting. Horan T.C., Andrus M., Dudeck M.A. Am J Infect Control. 2008;36:309-32

RAS as a positive predictive biomarker: focus on lung and colorectal cancer patients

Rat sarcoma (RAS) oncogenes have intensively been investigated during the last decades. Taking into account all human tumours, Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene is the most frequently mutated (about 22%) among the three isoforms, followed by Neuroblastoma RAS Viral Oncogene Homolog (NRAS) (8%) and Harvey Rat Sarcoma Viral Oncogene Homolog (HRAS) (3%). In the last years, careful attention has been paid on KRAS and NRAS gene mutations in non–small-cell lung cancer (NSCLC) and colorectal cancer (CRC) patients because of their prognostic and predictive roles. In particular, a large body of literature data has been generated investigating clinical outcomes of targeted treatments in NSCLC and CRC KRAS- and NRAS-mutated patients. The latest evidences are here reviewed, providing also an overview of the real-world RAS mutation testing practice across different Italian laboratories. On this basis, we propose a knowledge-based system, www.rasatlas.com, to support the healthcare personnel in the management of patients featuring RAS gene mutations in the landscape of precision oncology

Congenital hypothyroidism with eutopic thyroid gland : analysis of clinical and biochemical features at diagnosis and after re-evaluation

Context: In recent years changes in screening strategies for congenital hypothyroidism (CH) led to an increased detection of mild forms of CH, associated with eutopic thyroid gland. Objectives: We aimed to determine the clinical evolution of CH with eutopic thyroid gland and to find out prognostic factors at diagnosis and follow-up. Patients and Methods: We retrospectively analyzed agroup of84 children withCH andeutopic thyroid gland treated at our institution. They all underwent clinical re-evaluation after the age of 3, based on thyroid function testing after L-thyroxine therapy withdrawal, thyroid ultrasonography, and 123I scintigraphy with perchlorate discharge test. Genetic analysis was performed in selected cases. Results: At re-evaluation, 34.5% of patients showed permanent hypothyroidism and needed L-thyroxine reintroduction, 27.4% had persistent hyperthyrotropinemia (TSH5-10mU/L), and 38.1% had transient hypothyroidism. Major risk factors for permanent CH were prematurity, first-degree familial history of goiter/nodules, thyroid hypoplasia at diagnosis, and high L-thyroxine requirements at follow-up. Iodine organification defects were found in 29.7% of patients, 30% of whom harbored DUOX2 mutations. TSH receptor gene mutations were found in 8.7% of patients with persistent thyroid dysfunction and negative perchlorate discharge test. Conclusions: Only one-third of patients with CH and eutopic thyroid gland needed to continue L-thyroxine therapy after re-evaluation. A frequent finding was the persistence of mild hyperthy-rotropinemia. The evolution of CH remains difficult to predict, although different clinical features might suggest different outcomes. Mutations in the genes commonly linked to mild forms of CH were documented in a minority of cases. Copyrigh