Background
Youths disengaged from the education system and labour force (i.e. ‘Not in Education, Employment, or Training’ or ‘NEET’) are often at reduced capacity to flourish and thrive as adults. ...Developmental precursors to NEET status may extend back to temperamental features, though this – and possible mediators of such associations such as attention deficit hyperactivity (ADHD) symptoms and antisocial behaviours (ASB) – have yet to be directly tested. This study investigates if i) difficult temperament in toddlerhood associates with NEET status in adulthood and ii) different subdomains of ADHD (i.e. hyperactivity‐impulsivity vs. inattention) in late childhood and ASB in adolescence partially explain this pathway.
Methods
Participants were 6,240 mother‐child dyads (60.7% female) from the Avon Longitudinal Study of Parents and Children. Mothers reported on their child’s (a) difficult temperament (i.e. mood, intensity and adaptability) at age 2 and (b) ADHD symptoms at ages 8 and 10. Participants reported their own ASB at age 14 and NEET status in adulthood (ages 18, 20, 22 and 23).
Results
First, higher levels of difficult temperament in toddlerhood directly associated with an increased probability of being NEET in adulthood. Second, this effect was carried through hyperactivity‐impulsivity, but not inattention, in late childhood, and ASB in adolescence; this demonstrates differential contribution to the pathway between the ADHD dimensions, with symptoms of hyperactivity‐impulsivity playing a prominent role.
Conclusions
Early difficult temperament is a vulnerability factor for NEET status in adulthood. Our findings suggest that one developmental pathway for this vulnerability manifests through increased hyperactivity‐impulsivity in childhood and ASB in adolescence. Of note, difficult temperament, as measured here, reflects difficulties in emotional and behavioural self‐control (e.g. low adaptability and high intensity negative emotional expressions). Our results, therefore, suggest a prominent developmental role for lack of self‐control from toddlerhood onwards in increasing risk for NEET.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The recently developed PROSASH model is proving to be a useful tool in risk‐group discrimination in hepatocellular carcinoma (HCC) patients treated with sorafenib. Several studies highlighted that ...the neutrophil‐to‐lymphocyte ratio (NLR) is one of the most important predictors of survival in HCC patients treated with sorafenib. The aims of the present study were to validate the PROSASH model and determine whether the incorporation of inflammatory markers can improve risk stratification. This study included 438 patients. According to the four categories of the PROSASH model, median overall survival (OS) was 20.0, 14.9, 8.5 and 3.0 months respectively (P < .001). The Harrell's c for this categorized model was 0.621. NLR (cut‐off 3) stratified OS in each of the PROSASH categories. After reclassification, median OS was 21.0, 15.1, 8.2 and 4.1 months (P < .001). The Harrell's c increased from 0.621 to 0.673 (P = .001). Integrating NLR into the PROSASH model allowed a more accurate classification of the patients in the risk groups.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Since Italian liver allocation policy was last revised (in 2012), relevant critical issues and conceptual advances have emerged, calling for significant improvements. We report the results of a ...national consensus conference process, promoted by the Italian College of Liver Transplant Surgeons (for the Italian Society for Organ Transplantation) and the Italian Association for the Study of the Liver, to review the best indicators for orienting organ allocation policies based on principles of urgency, utility, and transplant benefit in the light of current scientific evidence. MELD exceptions and hepatocellular carcinoma were analyzed to construct a transplantation priority algorithm, given the inequity of a purely MELD‐based system for governing organ allocation. Working groups of transplant surgeons and hepatologists prepared a list of statements for each topic, scoring their quality of evidence and strength of recommendation using the Centers for Disease Control grading system. A jury of Italian transplant surgeons, hepatologists, intensivists, infectious disease specialists, epidemiologists, representatives of patients’ associations and organ‐sharing organizations, transplant coordinators, and ethicists voted on and validated the proposed statements. After carefully reviewing the statements, a critical proposal for revising Italy's current liver allocation policy was prepared jointly by transplant surgeons and hepatologists.
The authors present a critical proposal for the implementation of the current liver allocation policy in Italy developed following the results of a national Consensus Conference process aimed to revise, on the basis of scientific evidence, the best indicators for guiding organ allocation policies in the urgency, utility, and benefit models. See the editorial from Berg on page 2537.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In patients with chronic liver disease, the accuracy of ultrasound scan (US), spiral computed tomography (CT), magnetic resonance imaging (MRI), and alpha-fetoprotein (AFP) in diagnosing ...hepatocellular carcinoma (HCC) has never been systematically assessed, and present systematic review was aimed at this issue.
Pertinent cross-sectional studies having as a reference standard pathological examinations of the explanted liver or resected segment(s), biopsies of focal lesion(s), and/or a period of follow-up, were identified using MEDLINE, EMBASE, Cochrane Library, and CancerLit. Pooled sensitivity, specificity, and likelihood ratios (LR) were calculated using the random effect model. Summary receiver operating characteristic (SROC) curve and predefined subgroup analyses were made when indicated.
The pooled estimates of the 14 US studies were 60% (95% CI 44-76) for sensitivity, 97% (95% CI 95-98) for specificity, 18 (95% CI 8-37) for LR+, and 0.5 (95% CI 0.4-0.6) for LR-; for the 10 CT studies sensitivity was 68% (95% CI 55-80), specificity 93% (95% CI 89-96), LR+ 6 (95% CI 3-12),and LR- 0.4 (95% CI 0.3-0.6); for the nine MRI studies sensitivity was 81% (95% CI 70-91), specificity 85% (95%CI 77-93), LR+ 3.9 (95%CI 2-7), and LR- 0.3 (95% CI 0.2-0.5). The sensitivity and specificity of AFP varied widely, and this could not be entirely attributed to the threshold effect of the different cutoff levels used.
US is highly specific but insufficiently sensitive to detect HCC in many cirrhotics or to support an effective surveillance program. The operative characteristics of CT are comparable, whereas MRI is more sensitive. High-quality prospective studies are needed to define the actual diagnostic role of AFP.
Summary Ten cases of glioblastomas showing oncocytic changes are described. The tumors showed mononuclear to multinuclear cells and abundant, granular, eosinophilic cytoplasm. The cytoplasm of these ...same cells was filled by strongly immunoreactive mitochondria. At ultrastructure, numerous mitochondria, some of which were large, were evidenced in the cytoplasm of neoplastic cells. Finally, 9 of 10 of these cases had a significantly high mitochondrial DNA content compared with control tissue ( P < .01). It seems that, for these tumors, the designation of oncocytic glioblastoma is appropriate. To the best of our knowledge, oncocytic changes have not been previously reported in such neoplasms. Oncocytic glioblastomas have to be added to the long list of various tumors that can manifest “unexpected” oncocytic changes in different organs. Albeit failing to show statistical significance (log-rank test, P = .597; Wilcoxon test, P = .233), we observed a trend for longer median survival in oncocytic glioblastomas, when compared with “ordinary” glioblastomas (median survival of 16 versus 8.7 months). Thus, it seems that the definition of neoplasms showing oncocytic changes, currently based on classic morphological parameters (ie, histology, ultrastructure, and immunohistochemistry), can be expanded by including the quantitative assessment of mitochondrial DNA content.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To determine the accuracy of various ultrasonographic (US) signs for assessment of the degree of liver fibrosis, with histologic results as reference standard.
Three hundred consecutive asymptomatic ...patients with at least 6 months of increased levels of aspartate aminotransferase and/or alanine aminotransferase underwent liver US and biopsy. The estimated pretest probability of severe fibrosis or cirrhosis was 35%. Three US parameters were investigated: liver surface nodularity, caudate lobe hypertrophy, and pattern of hepatic venous blood flow. US results were compared with histologic results obtained after liver biopsy, which constituted the reference standard for diagnosis of severe fibrosis or cirrhosis. The degree of fibrosis was graded according to METAVIR criteria, with stages 3 and 4 considered together. Data were analyzed with kappa and chi2 statistics. Sensitivity, specificity, positive and negative likelihood ratios, and posttest probability were calculated for each US sign.
In 107 (36%) patients with severe fibrosis (n = 34) or cirrhosis (n = 73), liver surface nodularity had the highest diagnostic accuracy, with specificity of 95% and positive and negative likelihood ratios 11.6 and 0.51, respectively. When liver surface nodularity was considered alone, posttest probability of severe fibrosis or cirrhosis increased from 35% to 86%. When caudate lobe hypertrophy and hepatic venous blood flow were also taken into account, posttest probability increased by only 2% (ie, to 88%).
US determination of liver surface nodularity is an accurate method for identifying the subset of asymptomatic patients with severe liver fibrosis or cirrhosis, which indicates a worse prognosis.
Abstract
Rationale
Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary ...vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting.
Methods
The study enrolled 181 treatment-naive PAH patients with a 6- months (IQR 144-363 days) right heart catheterization and risk assessment after initial oral combination therapy.
Results
Group-A, 96 (53.0%) patients without cardiac comorbidities; Group-B, 54 (29.8%) patients with one cardiac comorbidity; Group-C, 31 (17.1%) patients with ≥2 cardiac comorbidities. Group-C patients were older with a balanced gender distribution. There was a significant difference in PVR reduction moving from the absence to one or ≥2 cardiac comorbidities, respectively, median -45.0%, -30.3%, -24.3%. A ERS/ESC low-risk status was present at first follow-up in 50 (52.0%) patients in Group-A, 19 (35.1%) in Group-B, and 9 (29.0%) in Group-C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group-A, 15 (27.7%) in Group-B, and 7 (22.6%) in Group-C. Group-A patients were 2.3 times more likely to achieve/maintain a low risk status compared with Group-B and -C (OR 2.27, 95% C.I. 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities.
Conclusion
Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment- induced decrease in PVR.
Prokineticin 2 (Prok2) or prokineticin-receptor2 (Prok-R2) gene mutations are associated with Kallmann syndrome (KS). We describe a new homozygous mutation of Prok-R2 gene in a man displaying KS with ...an apparent reversal of hypogonadism. The proband, offspring of consanguineous parents, presented at age 19 years with absent puberty, no sense of smell, low testosterone and gonadotrophin levels. Magnetic resonance imaging showed olfactory bulb absence. The patient achieved virilization and spermatogenesis with gonadotrophin administration. Two years after discontinuing hormonal therapy, he maintained moderate oligozoospermia and normal testosterone levels. Prok2 and Prok-R2 gene sequence analyses were performed. The proband had a homozygous mutation in Prok-R2 exon 2 that harbours the c.T820>A base substitution, causing the introduction of an aspartic acid in place of valine at position 274 (Val274Asp). His mother had the same mutation in heterozygous state. This report describes a novel homozygous mutation of Prok-R2 gene in a man with variant KS, underlying the role of Prok-R2 gene in the olfactory and reproductive system development in humans. Present findings indicate that markedly delayed activation of gonadotrophin secretion may occur in some KS cases with definite gene defects, and that oligozoospermia might result from a variant form of reversible hypogonadotrophic hypogonadism.
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