Three-Dimensional Printing Model Enhances Craniofacial Trauma Teaching by Improving Morphologic and Biomechanical Understanding: A Randomized Controlled Study.

BACKGROUND: Teaching about craniofacial traumas is challenging given the complexity of the craniofacial anatomy and the necessity for good spatial representation skills. To solve these problems, three-dimensional printing seems to be an appropriate educative material. In this study, the authors conducted a randomized controlled trial. The authors' main objective was to compare the performance of the undergraduate medical students in an examination based on the teaching support: three-dimensionally printed models versus two-dimensional pictures. METHODS: All participants were randomly assigned to one of two groups using a random number table: the three-dimensionally-printed support group (three-dimensional group) or the two-dimensionally-displayed support group (two-dimensional group). All participants completed a multiple-choice question evaluation questionnaire on facial traumatology (first, a zygomatic bone fracture; then, a double mandible fracture). Sex and potential confounding factors were evaluated. RESULTS: Four hundred thirty-two fifth-year undergraduate medical students were enrolled in this study. Two hundred six students were allocated to the three-dimensional group, and 226 were allocated to the two-dimensional group. The three-dimensionally printed model was considered to be a better teaching material compared with two-dimensional support. The global mean score was 2.36 in the three-dimensional group versus 1.99 in the two-dimensional group (p = 0.008). Regarding teaching of biomechanical aspects, three-dimensionally-printed models provide better understanding (p = 0.015). Participants in both groups exhibited similar previous student educational achievements and visuospatial skills. CONCLUSIONS: This prospective, randomized, controlled educational trial demonstrated that incorporation of three-dimensionally-printed models improves medical students' understanding. This trial reinforces previous studies highlighting academic benefits in using three-dimensionally-printed models mostly in the field of understanding complex structures.

Anemia management in non-menopausal women in a primary care setting: a prospective evaluation of clinical practice.

BACKGROUND: The study aimed to analyze anemia management in non-pregnant, and non-menopausal women aged from 18 to 50 years old, in a French primary care setting. METHODS: An observational descriptive prospective study was conducted between November 2018 and February 2019. Inclusion criteria were as followed: anemia diagnosed in women aged from 18 to 50, not pregnant and not menopausal. Quantitative and qualitative data were anonymized and collected through an electronic survey. Investigating general practitioners completed the questionnaire for each newly diagnosed woman. Mean values and medians were calculated for the quantitative data. Answers to the open questions were encoded manually and proportions of the different modalities have been calculated. RESULTS: Altogether, 43 women with anemia were ascertained. Moderate microcytic anemia, due to an iron deficiency in a context of menorrhagia, was the most observed anemia profile. The mean value of hemoglobin was 10.5 ± 1 g/dl. Among these women: 32 (74%) presented an iron deficiency, 17 (53%) had inappropriate intakes, and 9 (28%) reported menorrhagia. For 17 (40%) women, unnecessary or inappropriate exams were prescribed. The investigations did not allow to establish a differential diagnosis for 12 women (28%). Even for similar clinical situations, anemia management was variable. Among the women who presented iron deficiency, 15 (47%) were informed about an iron-rich diet and received a daily iron supplementation of ferrous sulfate between 80 mg and 160 mg. CONCLUSIONS: Our study highlights that, in the absence of specific national guidelines for anemia management in non-pregnant, non-menopausal women in primary care settings, French GPs undergo various clinical management strategies leading to a heterogeneous, sometimes inappropriate follow-up. Women with iron deficiency were prescribed higher daily iron supplementation than recommended, according to new evidence, suggesting a maximal daily dose of 50 mg of elementary iron in a context of Hepcidin up-regulation in the case of an iron overload. Additional longitudinal studies with a bigger sample size and randomized controlled trials are needed to confirm our results and to elaborate national guidelines.

Compared characteristics of current vs. past smokers at the time of diagnosis of a first-time lung or head and neck cancer: a cross-sectional study.

BACKGROUND: Active smoking at the time of diagnosis of a first head & neck (H&N) or lung cancer is associated with a worse cancer outcome and increased mortality. However, the compared characteristics of active vs. former smokers at cancer diagnosis are poorly known. METHODS: In 371 subjects with a first H&N or lung cancer, we assessed: 1) socio-demographic features; 2) lifelong types of smoking; 3) alcohol use disorder identification test (AUDIT); 4) cannabis abuse screening test (CAST); and 5) Mini International Neuropsychiatric Interview (MINI). Using a multivariable regression model, we compared the profile of current smokers and past smokers. RESULTS: Current smokers more frequently exhibited H&N cancer (OR 3.91; 95% CI [2.00-6.51]; p <  0.0001) and ever smoking of hand-rolled cigarettes (OR 2.2; 95% CI [1.25-3.88]; p = 0.007). Among subjects with lung cancer (n = 177), current smoking was primarily associated with ever smoking of hand-rolled cigarettes (OR 2.88; 95% CI [1.32-6.30]; p = 0.008) and negatively associated with age (OR 0.92; 95% CI [0.89-0.96]; p <  0.001). Among subjects with H&N cancer (n = 163), current smokers exhibited a significantly greater AUDIT score (OR = 1.08; 95% CI [1.01-1.16]; p = 0.03). CONCLUSION: At the time of diagnosis of the first lung or H&N cancer, current smoking is highly associated with previous type of smoking and alcohol drinking patterns. TRIAL REGISTRATION: NCT01647425 ; Registration date: July 23, 2012.

National Esophageal Atresia Register.

National Esophageal Atresia was created in 2008 by the National Reference Center for Esophageal Congenital Abnormalities created in 2006. Primary goal was estimation of live birth prevalence in France. A national network of surgeons and pediatricians was initiated and entire teams dealing with esophageal atresia accepted to participate in an exhaustive national register. A questionnaire was validated by a national committee and data were centralized in our center. Scientific exploitation showed that such database is useful for health authorities as for medical professionals. Live birth prevalence in France is at 1.9/10,000 births. Prenatal diagnosis is more common but its effect on prevalence is not yet fully understood. Associated congenital abnormalities are frequent and major malformations with termination of pregnancy can influence prevalence.

Telomere regulation during ageing and tumorigenesis of the grey mouse lemur.

Telomere erosion leading to replicative senescence has been well documented in human and anthropoid primates, and provides a clue against tumorigenesis. In contrast, other mammals, such as laboratory mice, with short lifespan and low body weight mass have different telomere biology without replicative senescence. We analyzed telomere biology in the grey mouse lemur, a small prosimian model with a relative long lifespan currently used in ageing research. We report an average telomere length by telomere restriction fragment (TRF) among the longest reported so far for a primate species (25-30 kb), but without detectable overall telomere shortening with ageing on blood samples. However, we demonstrate using universal STELA (Single Telomere Length Amplification) the existence of short telomeres, the increase of which, while correlating with ageing might be related to another mechanism than replicative senescence. We also found a low stringency of telomerase restriction in tissues and an ease to immortalize fibroblasts in vitro upon spontaneous telomerase activation. Finally, we describe the first grey mouse lemur cancer cell line showing a dramatic telomere shortening and high telomerase activity associated with polyploidy. Our overall results suggest that telomere biology in grey mouse lemur is an exception among primates, with at best a physiologically limited replicative telomere ageing and closest to that observed in small rodents.

Improvement of the initial management of sarcomas after the dissemination of evidence-based guidelines depends on the primary sarcoma location: a population-based study.

BACKGROUND: Improvement of the initial management of sarcomas after the dissemination of evidence-based guidelines depends on the primary sarcoma location: a population-based study. To improve the initial management of adult sarcomas, a regional expert team in Northern France performed two actions: dissemination of evidence-based guidelines (EBG) for the management of soft tissue/visceral sarcoma and yearly educational symposia. The aim of this study was to measure the impact of the dissemination of EBG on the key-indicators of adult sarcoma management. METHODS: We conducted a before-after population-based study (before: 2005 with 63 cases, after: 2008-2009 with 86 cases) in the Lille area (Northern France urban/sub-urban area with 800,000 inhabitants). The following were the key-indicators of adult sarcoma management: pre-therapeutic biopsy, appropriate tumour and chest imaging, expert interdisciplinary discussion, expert interdisciplinary discussion before the first treatment and in operated cases, the rate of R0 resection. RESULTS: There was no statistically significant difference in patient and tumour characteristics for the two time periods in terms of gender, prior cancer, primary location, histological subtype, grade, size, metastasis and lymph node involvement. There was no statistically significant improvement in primary tumour imaging (83 versus 87%), chest imaging (67 vs 71%), pre-therapeutic biopsy (57 vs 58%). There was an improvement in expert multidisciplinary discussion (37 vs 45%) or discussion before the first treatment (26 vs 44%) but no statistically significant. However, when soft tissue and bone sarcomas were analysed separately, we observed statistically significant improvements in expert multidisciplinary discussion (50 vs 74%, p = 0.02) and R0 resection rate (58 vs 91%, p = 0.002). In contrast, in cases of visceral sarcoma, there was no improvement in expert multidisciplinary discussion (10 vs 16%, p = 0.7) or in R0 resection (88 vs 81%, p = 0.7). CONCLUSIONS: The dissemination of EBG was associated with a limited improvement in sarcoma management when measured in this before-after population-based study, and this improvement was dependent on the primary location of the tumour. Efforts to implement these guidelines by all surgical teams that could treat sarcoma, including visceral sarcoma, need to be made.

Association between caffeine intake and age at onset in Huntington's disease.

Habitual consumption of caffeine, a non-selective adenosine receptor (AR) antagonist, has been suggested to be beneficial in Parkinson's and Alzheimer's diseases. Experimental evidence support that ARs play a role in Huntington's disease (HD) raising the hypothesis that caffeine may be a life-style modifier in HD. To determine a possible relationship between caffeine consumption and age at onset (AAO) in HD, we retrospectively assessed caffeine consumption in 80 HD patients using a dietary survey and determined relationship with AAO. Following adjustment for gender, smoking status and CAG repeat length, caffeine consumption greater than 190mg/day was significantly associated with an earlier AAO. These data support an association between habitual caffeine intake and AAO in HD patients, but further studies are warranted to understand the link between these variables.

Modifying effect of arterial hypertension on amyotrophic lateral sclerosis.

Given the high oxygen consumption of motor neurons, we sought to assess the frequency and prognostic value of arterial hypertension (affecting brain's oxygen supply) in amyotrophic lateral sclerosis (ALS). We consecutively and prospectively included all ALS patients with regular medical follow-up and documented blood pressure measurements and monitored them until death. Vascular factors diagnosed prior to the onset of motor signs in ALS patients were compared with those in a stratified, age- and gender-matched case-control population. The severity of leukoaraiosis on magnetic resonance imaging (MRI) was blindly assessed. Post mortem examinations were performed when authorized. Compared with controls (n = 408), the 102 ALS patients were significantly more likely to display hypertension (41-57%) and current smoking (15-26%). The number of years of hypertension was associated with survival (HR = 1.04 (1.01-1.07)). In a multivariate analysis, leukoaraiosis severity (HR = 1.214 (1.096-1.344)), current smoking (HR = 1.766 (1.085-2.872)) and low vital capacity (HR = 2.422 (1.266-4.633)) remained independent predictors of survival. Post mortem examinations revealed a greater frequency of leukoaraiosis in ALS patients (p = 0.02). In conclusion, the effect of chronic hypertension on survival might be exerted through abnormal neural perfusion. The higher frequency of recent hypertension in ALS patients may be due to a compensatory increase in blood pressure in response to a lower oxygen supply.

Treatment of vascular risk factors is associated with slower decline in Alzheimer disease.

BACKGROUND: There is growing evidence that vascular risk factors (VRF) contribute to cognitive decline. Whether their treatment can slow down the progression of Alzheimer disease (AD) remains unsettled. The aim of this observational study was to evaluate whether the treatment of VRF is associated with a slower cognitive decline in patients who have AD without cerebrovascular disease (CVD). METHODS: We recruited 301 consecutive patients who had AD without CVD (mean age 71.7 years; 69.4% women; first Mini-Mental State Examination [MMSE] mean score 21.6; mean follow-up 2.3 years), who had attended a memory clinic between 1997 and 2003. VRF sought were high blood pressure, dyslipidemia, diabetes mellitus, tobacco smoking, and atherosclerotic disease. Only 21 patients (7.0%) had no VRF. Others were classified as having no VRF treated (n = 72; 25.7%), some VRF treated (n = 119; 42.5%), or all VRF treated (n = 89; 31.8%). We compared MMSE progression over time among these 3 groups using a mixed random effects regression model. RESULTS: Baseline MMSE scores were similar in the 3 groups. With adjustment for confounding factors, MMSE progression over time differed significantly between groups (p = 0.002). Patients with all their VRF treated declined less than those with none of their VRF treated. Those with some VRF treated tended to have an intermediate decline. CONCLUSIONS: In patients who have Alzheimer disease without CVD, treatment of vascular risk factors (VRF) is associated with a slower decline in Mini-Mental State Examination score. Randomized controlled trials are needed to confirm this association, but our data suggest that dementia should not prevent treatment of VRF.

Genotype-phenotype correlations for exudative age-related macular degeneration associated with homozygous HTRA1 and CFH genotypes.

PURPOSE: Major genetic factors for age-related macular degeneration (AMD) have recently been identified as susceptibility risk factors, including polymorphisms of HTRA1 and CFH genes. The purpose was to analyze the angiographic features of patients harboring homozygous genotypes for HTRA1 and CFH genes in a French exudative AMD population. METHODS: Two hundred patients affected with exudative AMD were genotyped for the polymorphisms rs11200638 of the HTRA1 gene and rs10611710 of the CFH gene. Four homozygous groups were extracted from the entire cohort: double homozygous for wild-type alleles of both genes (group 1), homozygous for the polymorphism of the HTRA1 gene only (group 2), homozygous for the polymorphism of the CFH gene only (group 3), and double homozygous carriers for both polymorphisms (group 4). Choroidal neovascularization (CNV) was graded as classic and predominantly classic (PC), occult, minimally classic (MC), or retinal angiomatosis proliferation (RAP). RESULTS: Group 1 (n = 9) presented 44.4% classic and PC, 33.3% occult, 11.1% MC, and 11.1% RAP. Group 2 (n = 12) presented 50.0% classic and PC, 33.3% occult, no MC CNV and 16.7% RAP. Group 3 (n = 28) presented 10.7% classic and PC, 67.9% occult, 14.3% MC, and 7.1% RAP. Group 4 (n = 17) presented 29.4% classic and PC, 52.9% occult, 11.8% MC, and 5.9% RAP. Occult CNV or MC CNV was more frequently observed in group 3 than in group 2 (82.1% vs 33.3%; P < 0.02). Classic and PC CNV were more frequently observed in group 2 than in group 3 (50% vs. 10.7%; P < 0.03). CONCLUSIONS: This attempt at a genotypic-angiographic correlation in an exudative AMD sample suggests an association between occult or MC CNV and the CFH polymorphism and between classic and PC CNV and the HTRA1 polymorphism.

Serum hepatocyte growth factor levels predict long-term clinical outcome after percutaneous coronary revascularization.

AIMS: To evaluate, in patients referred for elective percutaneous coronary revascularization (PCR) without heparin pre-treatment, the relationship between baseline serum levels of the angiogenic growth factors, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and clinical outcome. METHODS AND RESULTS: In 488 consecutive patients undergoing elective coronary angioplasty, hsC-reactive protein, HGF, and VEGF levels were measured before heparin administration. The primary endpoint, a composite of death and myocardial infarction, occurred in 44 patients at a median follow-up of 14.9 months. At baseline, VEGF levels were related to C-reactive protein levels and inversely related to age; HGF levels were related to C-reactive protein levels, diabetes, and recent clinical instability. In the univariate analysis, HGF had a significant positive relationship (P=0.003) with the primary endpoint. A similar trend was observed for VEGF (P=0.11). The only three variables significantly associated with the primary endpoint in the multivariable Cox model were HGF (P=0.004), C-reactive protein (P=0.007), and diabetes (P=0.04). CONCLUSION: Our results demonstrate that in patients, without heparin pre-treatment, referred for PCR, a high serum level of HGF is an independent predictor of clinical events during follow-up and is correlated with other surrogate measures of the activity of atherosclerosis.

S18Y polymorphism in the UCH-L1 gene and Parkinson's disease: evidence for an age-dependent relationship.

We studied the relationship between Parkinson's disease (PD) and the S18Y polymorphism in the UCH-L1 gene and the effect on this relationship of age at onset, smoking, and pesticides. Patients requested free health coverage for PD to the Mutualité Sociale Agricole (MSA), the French health insurance organization for people whose work is related to agriculture. Controls requested reimbursement of health expenses to the MSA. A maximum of three controls were matched to each case. Analyses included participants with both parents born in Europe. There were no differences in S18Y genotypes between patients (n = 209; 67% SS, 32% SY, 1% YY) and controls (n = 488; 66% SS, 30% SY, 4% YY). The relationship between PD and S18Y was modified by age at onset (P = 0.03). The Y allele was inversely associated with PD for patients with onset before 61 years (odds ratio [OR] = 0.53; 95% confidence interval [CI], 0.29-0.99); there was no association for older patients (62-68 years: OR = 1.21; 95% CI, 0.67-2.20; >68 years: OR = 1.24; 95% CI, 0.67-2.31). Among patients, Y carriers had a later onset than noncarriers (P = 0.04). These findings were not modified or confounded by smoking and pesticides. In this community-based case-control study, carriers of the Y allele were at decreased risk of developing PD at a young age, independently of pesticides and smoking.

Association between Parkinson's disease and polymorphisms in the nNOS and iNOS genes in a community-based case-control study.

Excess of nitric oxide (NO) has been shown to exert neurotoxic impacts in the brain. Moreover, inhibition of two NO-synthesizing enzymes, neuronal NOS (nNOS) and inducible NOS (iNOS), displays neuroprotective effects in the MPTP model of Parkinson's disease (PD). These data suggest a possible involvement of NOS as factors controlling the resistance of the nigral dopaminergic neurons to environmental insults. Therefore, we investigated whether polymorphisms present in these genes could contribute to the risk of developing PD. We carried out a community-based case-control study among subjects enrolled in the Mutualité Sociale Agricole, the French health insurance organization for workers connected to agriculture. Two-hundred and nine PD patients and 488 controls of European (mostly French) ancestry and matched for age, sex and region of residency were included in this study. Associations were observed with polymorphisms present in exon 22 of iNOS (OR for AA carriers=0.50, 95% CI=0.29-0.86, P=0.01) and in exon 29 of nNOS (OR for carriers of the T allele=1.53, 95% CI=1.08-2.16, P=0.02); no association was observed with a polymorphism in exon 18 of nNOS (OR for carriers of the T allele=1.20, 95% CI=0.85-1.69, P=0.30). Moreover, a significant interaction of the nNOS polymorphisms with current and ever cigarette smoking was found (nNOS 18, P=0.05; nNOS 29, P=0.04). All together, these data favour an involvement of these two genes as new modifier genes in PD.