An immunogenomic exome landscape of triple positive primary antiphospholipid patients.

Primary antiphospholipid syndrome is characterized by thrombosis and autoantibodies directed against phospholipids or associated proteins. The genetic etiology of PAPS remains unknown. We enrolled 21 patients with thromboembolic events associated to lupus anticoagulant, anticardiolipin and anti ß2 glycoprotein1 autoantibodies. We performed whole exome sequencing and a systematic variant-based analysis in genes associated with thrombosis, in candidate genes previously associated with APS or inborn errors of immunity. Data were compared to public databases and to a control cohort of 873 non-autoimmune patients. Variants were identified following a state-of-the-art pipeline. Enrichment analysis was performed by comparing with the control cohort. We found an absence of significant HLA bias and genetic heterogeneity in these patients, including when testing combinations of rare variants in genes encoding for proteins involved in thrombosis and of variants in genes linked with inborn errors of immunity. These results provide evidence of genetic heterogeneity in PAPS, even in a homogenous series of triple positive patients. At the individual scale, a combination of variants may participate to the breakdown of B cell tolerance and to the vessel damage.

[Optimization of post-surgical wound by a multidisciplinary team: pilot feasibility study]. / Optimisation de la prise en charge de la plaie post-chirurgicale par une équipe pluridisciplinaire : étude pilote de faisabilité.

OBJECTIVES: The management of post-surgical wounds is complex and suffers from a lack of coordination between the hospital and the community. The pharmacist could improve the efficiency of the care pathway by optimizing the compliance of discharge orders (DO) with current standards and reducing the associated expenditures. The objective of this study was to evaluate the impact of a multidisciplinary intervention on the quality and cost of acute post-surgical wound management. METHODS: This is a pilot study, monocentric, prospective, before/after. Non-conformities (NC) of DO for post-surgical wounds were analyzed before and after a multidisciplinary intervention (development of protocols, provision of prescription aid supports, training) in 3 surgical departments. The cost of each OS filled in the community was collected and the satisfaction of community pharmacists was evaluated. RESULTS: Out of 120 OS collected, 576 NC were detected. The intervention halved the number of DO with at least 1 NC and divided the median number of NC per order by 7. Community pharmacists were 4 times more satisfied with the quality of DO after the intervention. The cost of the multidisciplinary intervention was estimated at 787 euro. This intervention did not change the average cost per prescription. CONCLUSION: The multidisciplinary intervention improved the quality of post-surgical wound management by making the hospital-city pathway more fluid. The intervention requires a low investment in human resources and could be economically interesting if the costs avoided by the prevention of complications were valued.

Relevance and Feasibility of a Personalized Dietary Intervention in Older People with Meals-On-Wheels: A Randomized Controlled Pilot Trial.

Objective: The present study aimed at assessing the feasibility and the effectiveness of a personalized dietary intervention in a meals-on-wheels service through a randomized controlled pilot trial. Design: Sixty recipients of home-delivered meals (75% of women; 70-97 years old) were recruited and randomly assigned to a control and an experimental group and followed over a period of 4 months. In the experimental group, the nutritional status (Mini-Nutritional Assessment - MNA questionnaire), the food intake and the food preferences were measured for each participant. Based on this screening, participants were provided with dietary guidance and follow-up. Those at risk of malnutrition were proposed enriched home-delivered meals. Enrichment was set up considering food preferences of the participants. Results: Looking at the whole sample at baseline, 80% (n=48/60) were at risk of malnutrition. Furthermore, 55% (n=33/60) ate less than 2/3 of their calorie and/or protein recommended allowances. In the experimental group, the intervention led to an increase of protein intakes and to a lower extent of calorie intake. In the control group, no significant changes were observed. Conclusion: To conclude, this study suggests that providing dietary guidance and adding nutrient-dense food to meals while considering food preferences is feasible and may help older beneficiaries of meals-on-wheels to increase calorie and protein intake and improve their nutritional status. However, there is a need to develop products or recipes to enrich the meals of the elderly more efficiently to achieve the recommended allowance.

Radiological assessment of mandibular invasion in squamous cell carcinoma of the oral cavity and oropharynx.

BACKGROUND: Preoperative assessment of mandibular bone invasion in squamous cell carcinoma of the oral cavity and oropharynx is crucial for optimizing bone resection. The principal aim of this study was to evaluate the diagnostic value of CT and MR imaging for the diagnosis of mandibular bone invasion compared to the histological reference. In addition, we assessed the survival impact of bone invasion. PATIENTS AND METHODS: A single-center retrospective study included all consecutive patients treated by mandibular bone interruption for squamous cell carcinoma of the oral cavity and/or oropharynx. RESULTS: Sixty-eight patients were included. Prevalence of bone invasion on histology was 43%. Sensitivity, specificity and positive and negative predictive value were respectively 70%, 71%, 66% and 76% for CT compared with histologic analysis, 83%, 50%, 59% and 78% for MRI, and 83%, 62% 62%, 83% for associated CT and MRI. The two tests showed good agreement, with kappa index 0.69 (95% CI, 0.49-0.89) (P<0.0001). There was no difference in overall survival (log-rank>0.70) between the groups with and without bone invasion. CONCLUSION: CT and MRI are complementary for preoperative assessment of mandibular bone invasion, be it cortical and/or medullary, and in some cases may allow mandibular bone-sparing.

Presence in head and neck cancer multidisciplinary team meeting: The patient's experience and satisfaction.

BACKGROUND: In oncology, multi-disciplinary team meetings improve overall survival and reduce time to treatment in head and neck cancer. Interestingly, no study has examined the experience of patients attending an MTM. The present study addressed two questions: Does the MTM cause anxiety/depression for patients who are present? Are patients satisfied at the end of the meeting? PATIENTS AND METHODS: The study included all patients attending an MTM, who agreed to participate in the study and who fully completed two questionnaires. The Hospital Anxiety and Depression Scale (HADS) and a satisfaction questionnaire were filled out at three time-points: T0 before MTM, T1 at end of MTM, and T2 1 month after MTM for the HADS; and T1 and T2 for the satisfaction questionnaire. RESULTS: There were no significant differences in the number of patients experiencing anxiety between T0 and T1 (P=0.6085), T0 and T2 (P=1) or T1 and T2 (P=1). Likewise, there were no significant differences in the number of patients in depression between T0 and T1 (P=0.9397), T0 and T2 (P=1) or T1 and T2 (P=1). Mean satisfaction was good (question 14 on the satisfaction questionnaire: 8.7/10 at T1 and 7.7/10 at T2), but with a significant decrease between T1 and T2 (P=0.0009: i.e.,<0.05). Percentage information remembered (question 12) significantly decreased between T1 (mean 86%, standard deviation 0.2, median 94%) and T2 (78%±0.2, median 81%) (P=0.03). Presence in the MTM did not appear to induce or increase anxiety or pre-existing depressive syndrome.

[Deep alkali burns: Evaluation of a two-step surgical strategy]. / Les brûlures profondes par agents basiques : évaluation d'une stratégie chirurgicale en deux temps.

INTRODUCTION: Chemical burns are rare but often lead to deep cutaneous lesions. Alkali agents have a deep and long lasting penetrating power, causing burns that evolve over several days. The local treatment for these patients is excision of the wound and split thickness skin graft. Early excision and immediate skin grafting of alkali burns are more likely to be complicated by graft failure and delayed wound healing. We propose a two-step method that delays skin grafting until two-three days after burn wound excision. RESULTS: Our population included 25 controls and 16 cases. Men were predominant with a mean age of 41.9 years. In 78% of cases, burns were located on the lower limbs. The mean delay between the burn and excision was 16.5 days. In cases, the skin graft was performed at a mean of 11.3 days after the initial excision. We did not unveil any significant difference between both groups for the total skin surface affected, topography of the burns and the causal agent. Wound healing was significantly shorter in cases vs controls (37.5 days vs 50.3 days; P<0.025). Furthermore, we observed a decreased number of graft failures in cases vs controls (13.3% vs 46.7%; P=0.059). CONCLUSION: Our study shows the relevance of a two-step surgical strategy in patients with alkali chemical burns. Early excision followed by interval skin grafting is associated with quicker wound healing and decreased rate of graft failure.

Prospective assessment of patients' knowledge and informational needs and of surgeon-to-patient information transfer before and after knee or hip arthroplasty.

BACKGROUND: Patients are playing an increasingly large role in their own management and must therefore receive clear, complete, and comprehensible information. In the field of hip and knee arthroplasty, little is known about the level of patient knowledge and effectiveness of surgeon-to-patient information transfer. We therefore designed a prospective observational study with the objective of assessing four factors: patient knowledge during management, quality of information transfer, informational needs, and factors associated with the level of knowledge. HYPOTHESIS: The level of patient knowledge changes during the management process. PATIENTS AND METHODS: A prospective single-centre study was conducted between January 2014 and March 2015 during the outpatient visits and inpatient stays of 63 patients who underwent arthroplasty of the hip (n=36) or knee (n=27). A single observer attended all patient visits and recorded the information provided by the surgeon. Each patient completed a self-questionnaire after the outpatient visit (T1), at admission (T2), and at discharge after surgery (T3). Semi-quantitative scores were used to assess knowledge and informational needs. The effectiveness of information transfer was evaluated by comparing the information provided by the surgeon to the replies made by the patients. RESULTS: The mean overall knowledge score (on a 0-42 scale) increased from 17.22±6.33 at T1 to 19.44±6.89 at T3 (P=0.0028). In contrast, knowledge about complications was better at T1 than at T3 (2.67±1.98 vs. 2.19±1.91; P<0.05). Agreement between information given by the surgeon and replies made by patients varied across items from 23% to 100%. The mean informational needs score (on a scale from 0 to 21) ranged from 3.67 to 4.83 and was higher at T3 than at T2 (4.83±3.77 vs. 3.67±4.86; P=0.03). The proportion of patients who wanted written information was higher at T3. Most patients sought information before the outpatient visit. At each step of the management process, the main areas about which the patients wanted information were the surgical procedure, the rehabilitation programme, and the prosthesis. Several socio-demographic or management-related factors influenced the level of knowledge. Thus, older age and lower educational attainment were associated with lower knowledge scores, whereas previous lower-limb orthopaedic surgery and amount of information provided by the surgeon were associated with higher knowledge scores. Knowledge scores were not associated with being employed vs. retired, gender, replacement of a hip vs. a knee, the surgeon, or being accompanied by another person. DISCUSSION: Our study is original in that we assessed changes in patient knowledge during the management process for hip or knee arthroplasty. The level of patient knowledge was fairly low and varied considerably across individuals and time points in the management process. These data highlight the importance of providing patients with information throughout their management and particularly at discharge, when the desire for information seems greatest. LEVEL OF EVIDENCE: IV, prospective observational study with no control group.

[Gadolinium-enhanced thoracic CTA: retrospective analysis of image quality and tolerability in 45 patients evaluated prior to the description of nephrogenic systemic fibrosis]. / Angioscanographie thoracique au gadolinium en TDM multicoupe du thorax: analyse rétrospective de la qualité image et de la tolérance chez 45 patients évalués antérieurement à la description de la fibrose systémique néphrogénique.

PURPOSE: To assess the accuracy and torerability of gadolinium-enhanced thoracic CTA using a 64 MDCT compared to a 16 MDCT. Because this study was started prior to the description of NSF, particular attention was paid to long-term follow-up of the patient population. MATERIALS AND METHODS: The study protocol was approved by the ethics committee of our institution and informed consent was obtained from all patients. Fourteen patients (Group 1) (9 males and 5 females; mean age: 64.3 years) with contraindication to the administration of iodinated contrast material underwent thoracic CTA (collimation: 32 x 2 x 0.6 mm; pitch: 1.2) with gadolinium administration (0.5 mml/ml) at 0.4 mmol/kg injected at 6 ml/sec with evaluation of clinical and biological tolerability of the gadolinium based contrast agent. Results from this patient population were compared to results from a population of 31 patients (21 males; 10 females; mean age: 63.2 years) (Group 2) imaged on a 16 MDCT. All patients were folloowed-up for a mean time of 22.6 months. RESULTS: Using a mean contrast volume (standard deviation) that was not significantly different (Group 1: 54.8+/-11 ml; Group 2: 53.4+/-6.9 ml) (p=0.94), patients in Group 1 underwent complete thoracic CTA whereas patients in Group 2 underwent CTA of only the middle third of the thoracic region. All CTA examinations were diagnostic for Group 1 and Group 2 patients; however, evaluation of subsegmental vessels was possible in a significantly larger proportion of patients in Group 1 (10/14; 72%) compared to Group 2 (6/31; 19%) (p=0.003). Mean attenuation values within pulmonary arterial branches were similar for Groups 1 and 2 (central arteries: 194.5+/-51.3 HU vs 180.6+/-53.8 HU; p=0.38) (lobar arteries: 208.5+/-52.5 HU vs 189.9+/-60.1 HU; p=0.33) (segmental arteries: 220.4+/-50.4 HU vs 201.5+/-54.7 HU; p=0.42). Transient alteration of renal function was recorded in one patient from Group 1 with severe pre-existing chronic renal failure. No change in renal function was observed for Group 2 patients. No case of NSF was reported in patients with pre-existing renal failure at the time of enrollment. CONCLUSION: The use of gadolinium-based contrast agent for thoracic CTA using a 64 MDCT provides diagnostic quality examinations in all patients with improved image quality compared to a 16 MDCT. No complication other than transient alteration of renal function was observed. Because the likelihood of developing NSF may vary with the type of gadolinium-based contrast agent used, the least toxic agent should be used.

Hypoadiponectinaemia and high risk of type 2 diabetes are associated with adiponectin-encoding (ACDC) gene promoter variants in morbid obesity: evidence for a role of ACDC in diabesity.

AIMS/HYPOTHESIS: Morbid obesity (BMI>40 kg/m(2)) affecting 0.5-5% of the adult population worldwide is a major risk factor for type 2 diabetes. We aimed to elucidate the genetic bases of diabetes associated with obesity (diabesity), and to analyse the impact of corpulence on the effects of diabetes susceptibility genes. METHODS: We genotyped known single nucleotide polymorphisms (SNPs) in the adiponectin-encoding adipocyte C1q and collagen-domain-containing (ACDC) gene (-11,391G>A, -11,377C>G, +45T>G and +276G>T), the peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala SNP and ACDC exon 3 variants in 703 French morbidly obese subjects (BMI 47.6+/-7.4 kg/m(2)), 808 non-obese subjects (BMI<30 kg/m(2)) and 493 obese subjects (30< or =BMI<40 kg/m(2)). RESULTS: Two 5'-ACDC SNPs -11,391G>A, -11,377C>G were associated with adiponectin levels (p=0.0003, p=0.008) and defined a "low-level" haplotype associated with decreased adiponectin levels (p=0.0002) and insulin sensitivity (p=0.01) and with a risk of type 2 diabetes that was twice as high (p=0.002). In contrast, the prevalence of the PPARG Pro12Ala was identical in diabetic and normoglycaemic morbidly obese subjects. The PPARG Pro12 allele only displayed a trend of association with type 2 diabetes in the non-obese group. ACDC exon 3 variants were associated with type 2 diabetes in the non-obese group only (odds ratio 7.85, p<0.0001). In contrast, the 5'-ACDC "low-level" haplotype was associated with type 2 diabetes in obese and morbidly obese subjects (odds ratio 1.73 and 1.92) but not in non-obese individuals. CONCLUSIONS/INTERPRETATION: These data clarify the contribution of the 5'-ACDC SNPs to the risk of diabesity. Their interaction with corpulence suggests for the first time a different genetic profile of type 2 diabetes in morbidly obese patients compared with in less obese individuals.

Effect of common polymorphisms in the HNF4alpha promoter on susceptibility to type 2 diabetes in the French Caucasian population.

AIMS/HYPOTHESIS: The gene encoding HNF-4alpha, an orphan nuclear receptor playing critical roles in embryogenesis and metabolism by regulating gene expression in pancreatic beta cells, liver, and other tissues, is localised to chromosome 20q13, where linkage to type 2 diabetes has been shown in multiple studies. As two reports have independently demonstrated a convincing association with variants adjacent to the HNF-4alpha P2 promoter in Finnish and Ashkenazi Jewish populations, we evaluated their contribution to diabetes risk in the French Caucasian population. METHODS: Genotypes for four haplotype tag SNPs were analysed for association with diabetes in a case-control study of 744 unrelated type 2 diabetic patients and 686 normoglycaemic subjects, and for linkage in 148 diabetic families in whom significant linkage to the HNF4alpha region had been shown. RESULTS: The association seen in the Finnish and Ashkenazi studies for SNPs rs2144908 and rs1884614 located within a haplotype block encompassing the beta cell promoter P2 of HNF-4alpha was not replicated in our study; in French Caucasians the minor allele prevalence was increased in control subjects [odds ratio (OR) 0.80, uncorrected p=0.022 for rs2144908; OR 0.82 uncorrected p=0.058 for rs1884614]. Furthermore, none of the SNPs tested in the French familial sample was associated with diabetes, nor do they appear to contribute to the linkage. CONCLUSIONS/INTERPRETATION: None of the previously associated SNPs confer an increased risk for diabetes in French Caucasians. A large meta-analysis of association studies will determine whether there is a consistent association between particular SNPs upstream of HNF-4alpha and type 2 diabetes in several ethnic groups.

Dissection of an inverted X(p21.3q27.1) chromosome associated with mental retardation.

In a 6 year old boy referred for mental retardation, fragile X syndrome was ruled out by cytogenetic and molecular analyses. Cytogenetic investigations revealed an inverted X chromosome (p21.3q27.1). A similar chromosomal rearrangement was detected in his mildly mentally retarded mother. Fluorescence in situ hybridization (FISH), using a panel of ordered YAC clones, allowed the identification of YACs spanning both the Xp21.3 and Xq27.1 breakpoints, where many non-specific mental retardation loci have been reported so far. Further investigations by FISH showed that the IL1RAPL1 gene at Xp21.3 was disrupted by the X chromosome inversion and therefore its inactivation may be related to the mental retardation observed in our patients.

Peripheral pulmonary arteries: how far in the lung does multi-detector row spiral CT allow analysis?

PURPOSE: To analyze the influence of multi-detector row spiral computed tomography (CT) on identification of peripheral pulmonary arteries. MATERIALS AND METHODS: Peripheral pulmonary arteries were analyzed on optimally opacified contrast material-enhanced spiral CT angiograms in 30 patients devoid of pleuroparenchymal disease who underwent scanning with multi-detector row CT (collimation, 4 x 1 mm; pitch, 1.7-2.0; scanning time, 0.5 second). Two series of scans were systematically generated from each data set, 1.25-mm-thick (group 1) and 3-mm-thick (group 2) sections, leading to the analysis of 600 segmental (20 arteries per patient), 1,200 subsegmental (40 arteries per patient), 2,400 fifth-order (80 arteries per patient), and 4,800 sixth-order (160 arteries per patient) pulmonary arteries in each group. RESULTS: Multi-detector row CT with reconstructed scans of 1.25-mm-thick sections (group 1) allowed (a) analysis of a significantly higher percentage of subsegmental arteries (94% in group 1 vs 82% in group 2; P <.001) and (b) a significantly higher percentage of fifth- and sixth-order arteries, respectively, identified in 74% and 35% of cases in group 1 and 47% and 16% in group 2 (P <.001). The causes for inadequate depiction of subsegmental branches in group 1 were partial volume effect (43%), anatomic variants (39%), and cardiac (17%) and respiratory (1%) motion artifacts. CONCLUSION: Multi-detector row CT with reconstructed scans of 1.25-mm-thick sections enables accurate analysis of peripheral pulmonary arteries down to the fifth order on spiral CT angiograms.

Molecular and cytogenetic characterisation of a small interstitial de novo 20p13-->p12.3 deletion in a patient with severe growth deficit.

We report on a small de novo interstitial deletion of the short arm of chromosome 20, 46,XY,del(20)(p12.3p13), in a young boy with hypotonia, moderate development delay, mild facial dysmorphism and severe growth failure. This patient did not show major features of Alagille-Watson Syndrome (AWS) which are common in more proximal 20p deletions. Standard and high resolution chromosome banding analysis revealed an apparent terminal deletion. Nevertheless, using chromosomal fluorescent in situ hybridization (FISH) and molecular analysis with polymorphic markers, we demonstrated that the abnormal chromosome resulted from a de novo interstitial deletion of paternal origin spanning from D20S842 to D20S900 and covering approximately 6 Mb. These findings indicate that a karyotype can lead to insufficient characterization of an apparently terminal deletion, and that one or a few genes in 20p13-->p12.3 bands are important for normal growth.

Identification and molecular characterization of a small 11q23.3 de novo duplication in a patient with Rett syndrome manifestations.

We report on an interstitial duplication of the long arm of chromosome 11 [46XX,dup(11) (q23.3)] in a girl with atypical Rett syndrome (RS). This case was discovered during a systematic cytogenetic study of RS. Fluorescent in situ hybridization including total chromosome painting and use of regional specific YAC, cosmid and plasmid probes, was used to confirm the chromosome 11q involvement and to identify the landmarks of the smallest 11q duplication reported to date. The findings are compared to cases of trisomy 11q reported previously, all of which have a larger duplication and different clinical manifestations. Surprisingly, mental retardation and behavior disorders are less severe in these cases.