Personality Changes With Dementia From the Informant Perspective: New Data and Meta-Analysis

Objective

To examine changes in personality in individuals with mild cognitive impairment (MCI) or dementia as observed by family members using both new data and a meta-analysis with the published literature.

A Rare Case of Late LAD Reimplantation after Arterial Switch Operation

Arterial switch operation (ASO) is a complex neonatal operation in which transfer of the coronary arteries origins is the key to success. Coronary events after a successful ASO are not uncommon. We describe a rare case of a child who underwent an ASO in the neonatal period with one coronary (LAD) described as atretic left in place. At age seven, he developed myocardial ischemia due to retrograde flow with a steal phenomenon from the LAD into the pulmonary artery. The patient underwent a late LAD reimplantation. This case underscores that even very small ostia should be translocated at the time of ASO.     

Investigating Canadian medical school attrition metrics to inform socially accountable admissions planning

Objective: Attrition from Canadian medical degree programs was never described despite differences in admissions requirements at the 17 faculties of medicine. Knowledge on attrition metrics could help the faculties evaluate new avenues for addressing the Association of Faculties of Medicine’s (AFMC) Future of Medical Education in Canada (FMEC MD) recommendation to enhance admissions practices with the goal to improve social accountability and student diversity.

Method: AFMC databases were used to track medical degree completion of all Canadian M.D. students who enrolled between 2003 and 2007. Students were followed and assigned an M.D. completion status as of by July 1, 2013. Bivariate statistics were used to evaluate if demographic, admission and degree progression variables were associated with medical school attrition.

Results: Of 11,454 students enrolled in Canadian M.D. programs from 2003 to 2007, only 197 (1.7%) did not complete. Québec had significantly higher attrition than other jurisdictions with age, educational attainment at time of enrolment, MCAT completion and struggling academically associated with attrition.

Conclusion: Attrition from Canadian MD programs is rare and associated with differences in admission requirements and possibly suggests an optimum life stage for medical studies. Improved knowledge of attrition-related factors may offer an additional level of evidence for improving the alignment between admissions policies and the social accountability objectives of medical schools.     

Association between hereditary predisposition to common cancers and congenital multimalformations

In a previous article we reported that mutations favoring cancer at adulthood seemed to improve fertility and limit miscarriages. Because spontaneous abortion may result from anomalies in embryo, we questioned if an increased frequency of congenital malformation could be evidenced among cancer-prone families. Oncogenetics database (≈193 000 members) of the comprehensive cancer center Jean Perrin was crossed with regional registry of congenital malformations (≈10 000). Among children born between 1986 and 2011, 176 children with malformation matched in both databases. In breast/ovaries cancer-prone families, the risk for malformations was multiplied by 2.4 [1.2-4.5] in case of a BRCA1 mutation. Frequencies of malformation in BRCA2 and MMR mutated families were similar to families without a cancer syndrome. In comparison to malformations concerning a unique anatomical system, multimalformations were significantly more frequent in case of BRCA or MMR mutations: compared to families without cancer syndrome, the risk of multimalformations was multiplied by 4.1 [0.8-21.7] for cancer-prone families but with no known deleterious mutation, by 6.9 [1.2-38.6] in families with a known mutation but an unknown parental mutational status and by 10.4 [2.3-46.0] when one parent carried the familial mutation. No association with the type of anatomical system was found, nor with multiple births. These results suggest that BRCA and MMR genes play an important role in human embryogenesis and that if their function is lowered because of heterozygote mutations, congenital malformations are either more likely (BRCA1 mutations) and/or more susceptible to concern several anatomical systems.     

Brain activation changes following motor training in children with unilateral cerebral palsy: An fMRI study

BackgroundIntensive motor-learning-based interventions have demonstrated efficacy for improving motor function in children with unilateral spastic cerebral palsy (USCP). Although this improvement has been associated mainly with neuroplastic changes in the primary sensori-motor cortices, this plasticity may also involve a wider fronto-parietal network for motor learning.ObjectiveTo determine whether hand-arm bimanual intensive therapy including lower extremities (HABIT-ILE) induces brain activation changes in an extensive network for motor skill learning and whether these changes are related to functional changes observed after HABIT-ILE.MethodsIn total, 25 children with USCP were behaviourally assessed in manual dexterity and everyday activities before and after HABIT-ILE. Functional imagery monitored brain activity while participants manipulated objects using their less-affected, more-affected or both hands. Two random-effects-group analyses performed at the whole-brain level assessed the brain activity network before and after therapy. Three other random-effects-group analyses assessed brain activity changes after therapy. Spearman's correlations were used to evaluate the correlation between behavioural and brain activity changes.ResultsThe same fronto-parietal network was identified before and after therapy. After the intervention, the more-affected hand manipulation elicited a decrease in activity on the motor cortex of the non-lesional hemisphere and an increase in activity on motor areas of the lesional hemisphere. The less-affected hand manipulation generated a decrease in activity of sensorimotor areas in the non-lesional hemisphere. Both-hands manipulation elicited an increase in activity of both hemispheres. Furthermore, we observed an association between brain activity changes and changes in everyday activity assessments.ConclusionBrain activation changes were observed in a fronto-parietal network underlying motor skill learning with HABIT-ILE in children with USCP. Two different patterns were observed, probably related to different phases of motor skill learning, representing an increased practice-dependent brain recruitment or a brain activation refinement by more efficient means.ClinicalTrials.govNCT01700777 & NCT02667613.     

Insomnia does not affect heart rate changes when young adults watch humorous films: An exploratory study

Emotional reactivity in insomnia is affected both subjectively and on a physiological level for negative emotional material, but little is known about reactions to positive stimuli. We here investigated whether in younger adult insomnia patients, presentation of short humorous films would lead to heart rate decreases during and after film viewing, as compared to heart rate changes when falling asleep. Investigating 20 participants with DSM‐5‐diagnosed insomnia and 18 participants without insomnia, we found that heart rate decreased when falling asleep, increased when watching humorous films and returned to normal values afterwards for all participants. Film‐related heart rate increases were strongly related to humour ratings of the films. No differences were found between those with and without insomnia on subjective ratings of the films, film‐related heart rate changes or when falling asleep. We conclude that the experience of positive daily life stimuli in younger adults is not affected by insomnia in our study, despite insomnia having a known more profound effect on negative stimuli. Future studies exploring insomnia‐related autonomous nervous system responses combining different neurophysiological modalities should confirm our findings.     

Histopathological growth patterns of resected non-colorectal,non-neuroendocrine liver metastases: a retrospective multicenter study

Background

Distinct Histopathological Growth Patterns can be identified in liver metastases from melanoma, breast and colorectal cancers. For each of these distinct liver metastasis types the HGP has proven a biomarker for survival after partial hepatectomy, with the desmoplastic type marking favourable prognosis. Whether HGPs can be considered a pan-cancer phenomenon remains unknown. This study therefore evaluates the presence of HGPs and their prognostic value across non-colorectal non-neuroendocrine liver metastases.

Methods

A retrospective multicentre cohort study was performed in patients who underwent curative intent resection of non-colorectal non-neuroendocrine liver metastasis. HGPs were assessed on Haematoxylin and Eosin slides according to consensus guidelines and classified as desmoplastic or non-desmoplastic. Overall- and recurrence-free survival were evaluated using Kaplan–Meier and multivariable Cox regression analysis.

Results

In total, 132 patients with liver metastasis from 25 different tumour types were eligible for analysis, of which 26 (20%) had a desmoplastic HGP. Five-year OS and RFS (95%CI) were 53% (36–78%) versus 40% (30–53%), and 33% (19–61%) versus 15% (9–27%) for patients with desmoplastic compared to non-desmoplastic metastases, respectively (p?=?0.031 & p?=?0.004). On multivariable analysis (adjusted HR [95%CI]) a desmoplastic HGP was prognostic for both OS (0.46 [0.25–0.86]) and RFS (0.38 [0.21–0.69]).

Conclusions

This study demonstrates that HGPs apply to liver metastases across a wide variety of primary tumour origins. They hold a prognostic value in these cases, suggesting that HGPs could represent a pan-cancer biomarker for survival after surgical resection of liver metastases.

     

MR imaging,targeting and characterization of pulmonary fibrosis using intra‐tracheal administration of gadolinium‐based nanoparticles

Idiopathic pulmonary fibrosis is a devastating disease. Animal models are critical to develop new diagnostic approaches. We investigate here whether the application of an ultra‐short echo time MRI sequence combined with the intra‐tracheal administration of Gd‐based nanoparticles can help to visualize and characterize pulmonary fibrosis in mice. 21 mice were imaged. Treated mice were administered bleomycin. MRI was used for longitudinal detection of bleomycin‐induced lung injury from Day 1 up to Day 60. On Day 30, all mice received nanoparticles and MR images were acquired. A signal enhancement of 120% and 50% in fibrotic lesions and healthy tissues respectively was obtained. A twofold increase of contrast‐to‐noise ratio between fibrotic and healthy tissue was also observed, leading to a more accurate delineation of the extent of fibrosis. The elimination time constant of the nanoparticles was 54% higher in fibrotic lesions. Bleomycin‐induced lung injury can be monitored using MRI. Intra‐tracheal administration of Gd‐based nanoparticles enabled us to enhance fibrotic tissue in lungs but also to extract imaging biomarkers that quantify elimination and diffusion of contrast agents and can characterize fibrotic tissue. The added value of MRI associated with pulmonary administration of contrast agents is key to better understand the lung fibrotic process and monitor drug response in pre‐clinical studies, which will be valuable for translational applications. Copyright © 2016 John Wiley & Sons, Ltd.     

Reduced encephalopathy in pigs with ischemia-induced acute hepatic failure treated with a bioartificial liver containing alginate-entrapped hepatocytes

OBJECTIVE: To analyze the effects of an extracorporeal bioartificial liver containing alginate bead-entrapped hepatocytes on pigs with ischemia-induced acute hepatic failure. DESIGN: Prospective animal study. SETTING: University and INSERM laboratory. SUBJECTS: Fifteen Large White/Pietrin female pigs weighing 20-30 kg. INTERVENTIONS: Acute hepatic failure was induced by end-to-side portocaval shunt and ligature of the whole porta hepatitis. The bioartificial liver was in a thermostabilized column, containing a fluidized bed of alginate beads that embedded porcine hepatocytes, connected to a plasmapheresis system. Intracranial pressure; survival; ammonia, total bilirubin, aminotransferases, alkaline phosphatase, and lactate concentrations; and clotting factors were studied. The groups were pigs with acute hepatic failure (group 1, n = 4), pigs with acute hepatic failure treated with bioartificial liver containing empty beads (group 2, n = 4), or porcine hepatocytes (group 3, n = 5). MEASUREMENTS AND MAIN RESULTS: In group 1, survival of pigs averaged 10.9 +/- 1.0 hrs; intracranial pressure reached 32.3 +/- 3.8 mm Hg and was associated with coma and cerebral edema. After connection to the bioartificial liver, the survival of acute hepatic failure pigs was 12.1 +/- 1.4 hrs in group 2 and 14.8 +/- 2.5 hrs in group 3. In group 3, intracranial pressure and bilirubin concentrations were reduced significantly compared with both group 1 and group 2. Neither signs of encephalopathy nor cerebral edema was observed in any animal of group 3. In all animals, plasma ammonium, aminotransferases, alkaline phosphatase, and lactate concentrations increased and clotting factors decreased with no significant differences between the three groups. Autopsy revealed a total necrosis of the liver, which was histologically confirmed. CONCLUSIONS: The ischemia-induced model of acute hepatic failure in pigs is reproducible and provides measurable clinical and biological features. A bioartificial liver containing alginate bead-entrapped hepatocytes improves the signs of encephalopathy in pigs with ischemia-induced acute hepatic failure, suggesting that the bioartificial liver can clear out toxic compounds that are released from necrotic livers.