Search

Background: The rate of growth of primary melanoma is a robust predictor of aggressiveness, but the mutational profile of fast-growing melanomas (FGMM) and the potential to stratify patients at high risk of death has not been comprehensively studied.Objective: To investigate the epidemiologic, clinical, and mutational profile of primary cutaneous melanomas with a thickness ≥ 1 mm, stratified by rate of growth.Methods: Observational prospective study. Deep-targeted sequencing of 40 melanoma driver genes on formalin fixed, paraffin-embedded primary melanoma samples. Comparison of FGMM (rate of growth > 0.5 mm/month) and nonFGMM (rate of growth ≤ 0.5 mm/month).Results: Two hundred patients were enrolled, among wom 70 had FGMM. The relapse-free survival was lower in the FGMM group (P = .014). FGMM had a higher number of predicted deleterious mutations within the 40 genes than nonFGMM (P = .033). Ulceration (P = .032), thickness (P = .006), lower sun exposure (P = .049), and fibroblast growth factor receptor 2 (FGFR2) mutations (P = .037) were significantly associated with fast growth.Limitations: Single-center study, cohort size, potential memory bias, number of investigated genes.Conclusion: Fast growth is linked to specific tumor biology and environmental factors. Ulceration, thickness, and FGFR2 mutations are associated with fast growth. Screening for FGFR2 mutations might provide an additional tool to better identify FGMM, which are probably good candidates for adjuvant therapies. [ABSTRACT FROM AUTHOR]

Encouraging recent reports on endovascular treatment of common femoral artery (CFA) atherosclerotic disease has rendered the question regarding the place of this technique evermore pertinent and legitimizes the performance of randomized trials. The present comprehensive review focused on the early and midterm outcomes to help assess the benefit/risk balance of endovascular vs open repair for CFA treatment. Embase and Medline searches were conducted according to the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analyses) standards to identify studies from 2000 to 2018 reporting on endovascular repair (ER), open surgery (OS), and comparisons of both techniques for CFA atherosclerosis treatment. The outcomes measured were 30-day mortality, morbidity, reintervention rates, midterm patency, late reintervention, and restenosis rates. Twenty-eight studies were eligible: 14 OS (1920 patients), 12 ER (1900 patients), and 2 comparative randomized trials (197 patients). The meta-analysis of the comparative studies revealed no differences in 30-day mortality or reintervention rates but improved 30-day morbidity after ER. At 1 year, the primary patency rates did not differ between ER and OS, nor did the late reintervention rate. In the noncomparative studies, with a mean follow-up period of 23.8 months for ER and 66 months for OS, the restenosis rate was 14.4% and 4.7%, respectively. The reported stent fracture rate was 3.6%. In the ER cohort, the overall primary patency at 1, 2, and 3 years was 81.9%, 77.8%, and 75.1%, respectively. For the OS cohort, the overall primary patency rate at 1, 2, and 3 years was 93.4%, 91.4%, and 90.5%, respectively. Despite expectations, our analysis of the reported data suggests that the perioperative mortality is not in favor of ER; however, the perioperative morbidity showed an advantage for ER compared with OS. Also, although comparable in the first year, the long-term primary patency rate was much greater after OS. At present, the place of ER for CFA treatment still requires further definition. Additional clarification of the indications and more research are both required to determine the optimal endovascular technology and femoral bifurcation reconstruction with stenting. [ABSTRACT FROM AUTHOR]

Screening and care for victims of sexual violence (SV) among asylum seekers and refugees (ASRs) living in High-income host countries were prioritized by the WHO in 2020. The lack of stabilized prevalence findings on lifetime SV among ASRs in High-income countries hinders the development of adequate health management. The objective of this study was to determine the lifetime prevalence of SV experienced by ASRs living in High-income countries. We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included in the meta-analysis if the sample consisted exclusively of asylum seekers or refugees over the age of 16 living in High-income countries and if they reported a lifetime prevalence of experienced SV. The results of the meta-analysis were expressed with 95 % confidence intervals (CIs) as estimates of lifetime SV prevalence using a random-effects model. The estimated lifetime prevalence of SV among women ASRs was 44 % (95 % CI, 0.24–0.67) and 27 % (95 % CI, 0.18–0.38) for both sexes. This meta-analysis revealed a high prevalence of SV among ASRs hosted in High-income countries and suggest the importance of developing specific screening and care programs in these host countries. [ABSTRACT FROM AUTHOR]

To determine the quality of life and neuropsychological development of school-aged children with Hirschsprung's disease. In this observational monocentric study, a multidisciplinary team prospectively assessed quality of life, neuropsychometric development and bowel functional outcomes. This study was registered on ClinicalTrial.gov (NCT03406741). Kidscreen and VSP-A questionnaires assessed the quality of life and were compared to the reference population (Eurostat database). Intelligence, attention and executive functions, perceptual organization and memory were evaluated using the Wechsler Children's Intelligence Scale, the NEuroPSYchological assessment, and the Rey figure test. Bowel functional outcomes were obtained using the Krickenbeck score. Fifteen patients were included, with a mean age of 10.25 years. The children's Kidscreen-assessed quality of life index was higher than the reference population (p = 0.01). The Full-Scale Intelligent Quotient was dissociated in 64% of children. The Perceptional Reasoning Index and the Processing Speed Index were observed at lower levels. There were no disturbances in executive functions. A satisfactory bowel functional outcome was noted in 46.7% of children. Children with Hirschsprung's disease have been shown to have subtle decreased performances in some areas of intelligence. Performing a neuropsychological assessment upon entering elementary school could help to detect these specific learning disabilities. Level II, prognosis study. [ABSTRACT FROM AUTHOR]

Background The respective place of endovascular repair (ER) versus open surgery (OS) in thoracic dissecting aneurysm treatment remains debatable. This comprehensive review seeks to compare the outcomes of ER versus OS in chronic type B aortic dissection treatment. Methods Embase and Medline searches (2000 to 2017) were performed following PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) guidelines. Outcomes data extracted comprised (1) early mortality and major complications: stroke, spinal cord ischemia (SCI), dialysis, and respiratory complications; and (2) late survival and reinterventions. Reintervention causes were divided into proximal, adjacent, and distal. Comparative studies allowed comparative meta-analysis. Noncomparative studies were analyzed in pooled proportion meta-analyses for each group. Results A total of 39 studies were identified after exclusions, of which 4 were comparative. Comparative meta-analysis demonstrated lower early mortality for ER (odds ratio [OR], 4.13; 95% confidence interval [CI], 1.10 to 15.4), stroke (OR, 4.33; 95% CI, 1.02 to 18.35), SCI (OR, 3.3; 95% CI, 0.97 to 11.25), and respiratory complications (OR, 6.88; 95% CI,1.52 to 31.02), but higher reintervention rate (OR, 0.34; 95% CI, 0.16 to 0.69). Midterm survival was similar (OR, 1.19; 95% CI, 0.42 to 3.32). Noncomparative studies demonstrated that most reinterventions were related to the aortic segment distal to primary intervention in both groups (OS 73%, ER 59%). Reintervention procedures were mainly surgical for OS (85%), mainly endovascular for ER (75%). Rupture rates were 1.2% (OS) and 3% (ER). Conclusions Endovascular repair is associated with significant early benefits, but this is not sustained at midterm. Reintervention is more frequent, but the OS is not exempt from reintervention or late rupture. Both techniques have their place, but patient selection is key. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the status of congenital diaphragmatic hernia (CDH) management in France and to assess predictors of adverse outcomes.Study Design: We reviewed the first-year outcome of all cases of CDH reported to the French National Register in 2011.Results: A total of 158 cases were included. Of these, 83% (131) were prenatally diagnosed, with a mortality rate of 39% (44 of 112) for live born infants with a known outcome at hospital discharge. Mortality increased to 47% (60 of 128) including those with termination of pregnancy and fetal loss. This contrasts with the 7% (2 of 27) mortality rate of the patients diagnosed postnatally (P = .002). Mortality worsened with 1 prenatal marker of CDH severity (OR 3.38 [1.30-8.83] P = .013) and worsened further with 2 markers (OR 20.64 [5.29-80.62] P < .001). Classic postnatal risk factors of mortality such as side of hernia (nonleft P = .001), prematurity (P < .001), low birth weight (P = .002), and size of the defect (P < .001) were confirmed. Of the 141 live births (114 prenatal and 27 postnatal diagnosis) with known outcomes, 93 (67%) survived to hospital discharge, 68 (60%) with a prenatal diagnosis and 25 (93%) with a postnatal diagnosis. The median time to hospital discharge was 34 days (IQR, 19.25-62). Of these survivors, 71 (76%) were followed up for 1 year.Conclusions: Despite advances in management of CDH, mortality was high and associated with prenatal risk factors. Postnatally, severe persistent pulmonary hypertension was difficult to predict and presented persistent challenges in management. [ABSTRACT FROM AUTHOR]

Single-port laparoscopy (SPL) was developed approximately 30 years ago in minimally invasive surgery. Literature comparing SPL with conventional laparoscopy (CL) for adnexal surgery (i.e., cystectomy and adnexectomy) is inconsistent. The objective of this systematic review and meta-analysis was to evaluate the advantage of SPL over CL for adnexal surgery. PubMed, Embase, and MEDLINE were searched for publications in English and in French published between 1975 and November 2015 using the following key words: (((single port) or (single site) or (one port) or (single-port access laparoscopy) or (single-site laparoscopy) or (laparoscopic single-site surgery)) and ((adnexal disease) or (ovarian cystectomy) or (ovariectomy) or (adnexectomy))) not (pregnancy). The primary outcome was postoperative pain assessed at 24 hours postsurgery. The secondary outcomes were postoperative pain at 6 and 48 hours postsurgery, analgesic consumption, operative time, blood loss, laparotomy conversion rate, mean hospital stay, and cosmetic results at 1 month. Sixteen relevant articles were identified by electronic search. The pooled analysis of randomized trials showed no significant difference between SPL and CL in terms of postoperative pain at 6 and 24 hours, blood loss, mean length of hospital stay, cosmetic results, and laparotomy conversion rate; however, operative time was longer for SPL (p = .03). The pooled analysis including all the selected studies showed no significant difference for all of these outcomes. This review and meta-analysis found no significant difference between SPL and CL for adnexal surgery, except for operative time. Further large-scale randomized trials should be conducted to investigate the potential advantages of SPL over CL before this laparoscopic approach can be recommended. [ABSTRACT FROM AUTHOR]

Background The efficacy and safety of treating elderly patients with colorectal cancer (CRC) is of concern. This study aimed to compare the short- and long-term outcomes of elective laparoscopic vs. open surgery to treat CRC in very elderly patients. Methods All patients aged >80 years and who had undergone a colectomy for CRC without metastasis between July 2005 and April 2012 were considered for inclusion. Demographic, clinical, operative, and postoperative data, plus overall and disease-free survival rates, were retrospectively collected and compared between two groups of patients that underwent an open procedure (OP group) or laparoscopy (LG). Results 123 patients were enrolled (55 OPG, 68 LG). Median age was similar between the groups (84 vs. 83 years, respectively; NS). Duration of surgery was significantly lower in OPG (170 vs. 200 min; p = 0.030). Overall mortality at 3 months was 8.3%: it tended to be greater in the OPG (16.5% vs. 1.5%, NS). Morbidity was significantly greater in the OPG compared to the LG (52.7% vs. 27.5%; p = 0.021), resulting in significantly longer hospital stay (12 vs. 8 days, respectively; p < 0.001). Pathological findings were similar between the two groups. Cumulative overall survival rates at 3 and 5 years were significantly greater after laparoscopy (85% and 72%) compared to open surgery (58.2% and 48%, respectively; p < 0.001). Conclusions Our study suggests that laparoscopy is safe and could increase overall survival compared to open surgery in elderly patients suffering from CRC. Summary This retrospective study compared the short- and longer-term outcomes of patients aged >80 years and undergoing elective laparoscopic or open surgery for CRC between 2005 and 2012. [ABSTRACT FROM AUTHOR]

Midtrimester sonographic short cervix is a good predictor of preterm birth in singleton pregnancies. This study aimed to assess the impact of implementing a universal transvaginal cervical length screening program on preterm birth rate. This study consisted of 2 parts: a before-and-after multicenter study and a study on the ECHOCOL ("echo"="ultrasound" and "col"="cervix" in French) prospective cohort. We compared the rate of preterm birth before and after the introduction of universal cervical length screening at the time of midtrimester anatomy ultrasound. The multicenter before-and-after regional study included all women with a singleton pregnancy who gave birth after 24 weeks' gestation in the South East of France from January 1, 2012 to April 30, 2018. In parallel, the ECHOCOL cohort study was prospectively conducted from May 2015 to July 2018, including 17 maternity hospitals in the South East region of France. In case of asymptomatic short cervix <25 mm, treatments offered included 200 mg of vaginal progesterone, or cerclage, or a pessary until 34 weeks' gestation. We observed a significant decrease rate of preterm birth between periods A and B after multivariate analysis. (respectively, 5.8% vs 5.6%; adjusted odds ratio, 0.92; 95% confidence interval, 0.89–0.95; P <.0001). In parallel, the percentage of cervical length screening significantly increased from 28.9% in period A to 52.9% in period B (odds ratio, 2.76; 95% confidence interval, 2.71–2.80; P <.0001). Among the 3468 patients of the ECHOCOL prospective cohort, 38 (1.1%) asymptomatic short cervices were detected, and 192 patients gave birth prematurely (11 with an asymptomatic short cervix and 181 without). In the ECHOCOL cohort, a marked but statistically insignificant tendency toward a reduced rate of preterm birth before 37 weeks of gestation was observed (from 5.8% to 5.5%; adjusted odds ratio, 0.72; 95% confidence interval, 0.51–1.03; P =.068). This study showed a significantly lower rate of preterm birth after the implementation of a universal cervical length screening and treating policy during the second trimester of pregnancy. The clinical trial was registered under NCT02598323. [ABSTRACT FROM AUTHOR]

Purpose Dilutions of intravenous medications may be inaccurate. The mixing technique may be a crucial factor. Design Three factors of dilution were tested: volume for dilution (large vs small), method for mixing (shaking vs inversion), and number of maneuvers (3 times vs 10). Methods Dilutions of glucose in saline solution were made by nurses, after a random factorial plan. The judgment criteria were the comparison between measured (Cmes) and expected (Cexp) concentration. Finding Cmes (n = 40) ranged from 89.5% to 123.6% of Cexp and was more accurate when made with a large volume (98.4% of Cexp vs 106.5%) and when mixed by inversion (100.6% of Cexp vs 104.6%). Conclusions Inversion rather than shaking and dilution in a large volume is a simple procedure for bedside medication preparation that allows better accuracy. The 3 versus 10 mixing procedures resulted in the same accuracy, which may be important for these time-consuming procedures. These results should be confirmed in clinical situations. [ABSTRACT FROM AUTHOR]

Background Surgical site infection (SSI) after neurosurgery has potentially devastating consequences. Methods A prospective cohort study was conducted over a period of 24 months in a university center. All adult patients undergoing neurosurgical procedures, with exception of open skull fractures, were included. Multivariate logistic regression analysis was used to identify independent risk factors. Results We included 949 patients. Among them, 43 were diagnosed with SSI (4.5%). A significant reduction in postneurosurgical SSI from 5.8% in 2009 to 3.0% in 2010 ( P = .04) was observed. During that period, an active surveillance with regular feedback was established. The most common microorganisms isolated from SSI were Staphylococcus aureus (23%), Enterobacteriaceae (21%), and Propionibacterium acnes (12%). We identified the following independent risk factors for SSI postcranial surgery: intensive care unit (ICU) length of stay ≥7 days (odds ratio [OR] = 6.1; 95% confidence interval [CI], 1.7-21.7), duration of drainage ≥3 days (OR = 3.3; 95% CI, 1.1-11), and cerebrospinal fluid leakage (OR = 5.6; 95% CI, 1.1-30). For SSIs postspinal surgery, we identified the following: ICU length of stay ≥7 days (OR = 7.2; 95% CI, 1.6-32.1), coinfection (OR = 9.9; 95% CI, 2.2-43.4), and duration of drainage ≥3 days (OR = 5.7; 95% CI, 1.5-22). Conclusion Active surveillance with regular feedback proved effective in reducing SSI rates. The postoperative period is associated with overlooked risk factors for neurosurgical SSI. Infection control measures targeting this period are therefore promising. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to assess the effects of operative indication, anatomy, and stent graft on type I endoleak occurrence after thoracic endovascular aortic repair. Methods A retrospective review was conducted of patients admitted for thoracic endovascular aortic repair between 2007 and 2013. All computed tomography angiography imaging was analyzed for the presence of endoleak and measurement of diameters and lengths. Variables studied included underlying disease, emergency, achieved aortic neck length, difference between proximal and distal neck diameters, landing zone 2, and stent graft characteristics (diameter, number, type of device, oversizing degree, and covered aorta length). Results The study population involved 84 patients (mean age, 56 years; range, 17-94 years) who were treated for thoracic aortic aneurysm (TAA) (n = 29; 34.5%), traumatic aortic rupture (n = 27; 32%), type B aortic dissection (n = 19; 22.5%), intramural hematoma (n = 2; 2%), penetrating aortic ulcer (n = 5; 6%), and aortoesophageal fistula (n = 2; 2%). Of these, 60 patients (71.5%) were treated emergently and 24 (28.5%) electively. Primary type I endoleak was noted in eight patients (9.5%), of which two resolved spontaneously. After a mean follow-up of 32 months (range, 3-76 months), secondary type I endoleak was detected in four patients (4.5%). All of them occurred after emergent TAA treatment. Comparison between emergent and elective groups revealed no significant differences in neck length (19.5 mm vs 26.5 mm; P = .197), oversizing degree (11.1% vs 10.9%; P = .811), or endoleak rates (13.3% vs 8.3%; P = .518). Hemorrhagic shock was not predictive of endoleak ( P = .483). Cox regression analysis of the different anatomic and stent graft-related factors revealed short proximal landing zone as the unique independent predictor of type I endoleak (hazard ratio, 0.89; 95% confidence interval, 0.81-0.99; P = .032). Conclusions Endoleak risk seems not to be increased by an emergency setting. However, the relatively high rate of late endoleak observed after emergent TAA repair advocates for close follow-up, contrary to traumatic aortic rupture. Furthermore, regardless of the pathologic process, a longer proximal landing zone is likely to guarantee early and late success. [ABSTRACT FROM AUTHOR]

Objective The study objective was to determine contemporary early outcomes associated with pneumonectomy for lung cancer and to identify their predictors using a nationally representative general thoracic surgery database (EPITHOR). Methods After discarding inconsistent files, a group of 4498 patients who underwent elective pneumonectomy for primary lung cancer between 2003 and 2013 was selected. Logistic regression analysis was performed on variables for mortality and major adverse events. Then, a propensity score analysis was adjusted for imbalances in baseline characteristics between patients with or without neoadjuvant treatment. Results Operative mortality was 7.8%. Surgical, cardiovascular, pulmonary, and infectious complications rates were 14.9%, 14.1%, 11.5%, and 2.7%, respectively. None of these complications were predicted by the performance of a neoadjuvant therapy. Operative mortality analysis, adjusted for the propensity scores, identified age greater than 65 years (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.5-2.9; P < .001), underweight body mass index category (OR, 2.2; 95% CI, 1.2-4.0; P = .009), American Society of Anesthesiologists score of 3 or greater (OR, 2.310; 95% CI, 1.615-3.304; P < .001), right laterality of the procedure (OR, 1.8; 95% CI, 1.1-2.4; P = .011), performance of an extended pneumonectomy (OR, 1.5; 95% CI, 1.1-2.1; P = .018), and absence of systematic lymphadenectomy (OR, 2.9; 95% CI, 1.1-7.8; P = .027) as risk predictors. Induction therapy (OR, 0.63; 95% CI, 0.5-0.9; P = .005) and overweight body mass index category (OR, 0.60; 95% CI, 0.4-0.9; P = .033) were protective factors. Conclusions Several risk factors for major adverse early outcomes after pneumonectomy for cancer were identified. Overweight patients and those who received induction therapy had paradoxically lower adjusted risks of mortality. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to develop a functional remission threshold for the Functional Remission Of General Schizophrenia (FROGS) scale, and test its validity regarding clinical and quality of life outcomes. Methods: Design: Cross-sectional study. Inclusion criteria: Schizophrenia according to DSM-IV-TR criteria. Data collection: Functioning was assessed using the FROGS and the Global Assessment of Functioning (GAF) scales; psychotic symptoms using the Positive and Negative Syndrome Scale; memory, attention, and executive functions were assessed using the California Verbal Learning Test, the D2 attention task, the Stroop color-word test, the verbal fluency test, the Trail Making Test A and B and the Wechsler Adult Intelligence Scale; and quality of life using the schizophrenia quality of life (S-QoL 18) scale. Analysis: A logistic regression analysis including the different dimensions of the FROGS was used to create a composite score to classify patients into remitted and non-remitted according a gold standard (cut-off: GAF N = 61). Receiver operating characteristics analyses were then performed to determine the area under the curve (AUC). Results: Of 137 patients enrolled, 26 were functionally remitted and 111 were not remitted according to GAF score. The AUC for the combination of the FROGS's dimensions to detect functional remission was 0.903 (p b 0.001). Sensitivity and specificity for the combination of the FROGS dimensions using the Youden index were 88.5 [69.8; 97.6] and 81.1 [72.5; 87.9], respectively. Validity of this combination was satisfactory. Patients in functional remission had a lower severity of the disease, especially for PANSS negative (p b 0.001) and general psychopathology (p b 0.001) symptoms. Only two cognitive functions (i.e. fluency and episodic memory) were improved in remitted patients. Higher quality of life levels were globally associated with better functioning. [ABSTRACT FROM AUTHOR]

Objectives: This study was designed to define the hyperresponse to thienopyridine (very low on-treatment platelet reactivity [VLTPR]) as the most predictive threshold value of platelet reactivity index vasodilator-stimulated phosphoprotein (PRI VASP) for the prediction of non-access site–related bleeding events. We also aimed to identify predictors of bleeding and VLTPR in patients treated with thienopyridines. Background: New P2Y12 blockers and platelet monitoring has been proposed to optimize platelet inhibition after acute coronary syndromes and improve ischemic outcomes. However, bleeding complications remain the Achilles’ heel of antiplatelet therapy, and platelet monitoring could be useful to evaluate this risk. Methods: A total of 1,542 consecutive patients undergoing coronary stenting for ACS were included in the present study (287 taking clopidogrel 75 mg, 868 taking clopidogrel 150 mg, and 387 taking prasugrel 10 mg). Results: During 6-month follow-up, 9% of patients (n = 139) experienced nonaccess site–related Bleeding Academic Research Consortium bleeding complications. These patients were more often women and nondiabetic and had lower PRI VASP values than others (p < 0.001). Receiver-operating characteristic curve analysis (0.71, p < 0.01) identified a threshold value for VLTPR of PRI VASP ≤10% to predict bleeding events with a sensitivity of 17% and a specificity of 97%. Although prasugrel was the main predictor of VLTPR in the whole population (odds ratio: 10.2, 95% confidence interval: 3.0 to –34.2; p < 0.001), VLTPR was the strongest and independent predictor of bleeding (odds ratio: 4.7, 95% confidence interval: 2.7 to 8.3; p < 0.001). Conclusions: The present study identified VLTPR (PRI VASP ≤10%) as the strongest predictor of bleeding complications in patients treated with thienopyridines. This marker could be useful for tailored therapy and bleeding prevention. [Copyright &y& Elsevier]

Study Objective: The technical conduct of total laparoscopic hysterectomy (LH) is critical to surgical outcomes. This study explored the validity evidence of an objective scale specific to the assessment of technical skills (H-OSATS) for 7 tasks of an LH with salpingo-oophorectomy procedure performed in the operating room.Design: Observational cohort study.Setting: Two academic hospitals in Marseille and Montpellier, France.Patients: Three groups of operators (novice, intermediate, and experienced surgeons) were video recorded during their live performances of LH on a simple case. For each group, a dozen unedited videos were obtained for the following tasks: division of the round ligament, division of the infundibulopelvic ligament, creation of the bladder flap, opening of the posterior peritoneum, division of the uterine vessels, colpotomy, and closure of the vault.Interventions: Two qualified raters blindly assessed each video using the H-OSATS rating scale. Inter-rater reliability and test-retest reliability were calculated as measures of internal structure. In a separate round of evaluations, the raters provided a global competent/noncompetent decision for each performance. As a measure of consequential validity, a pass/fail score was set for each task using the contrasting group method.Measurements and Main Results: Three tasks (creation of the bladder flap, colpotomy, and closure of the vault) displayed sound validity evidence: a meaningful total score difference among the 3 groups of experience as well as between the intermediate and experienced surgeons, reliability outcomes of >0.7, and a pass/fail score with a theoretical false-positive rate of <10%.Conclusion: The validity evidence of the H-OSATS rating scale differed for separate evaluations of the 7 tasks. Three tasks (i.e., creation of the bladder flap, colpotomy, and closure of the vault) revealed sound validity evidence, including at the level of the attending surgeon, whereas other tasks were more consistent with low-stakes formative evaluation standards. [ABSTRACT FROM AUTHOR]

Objective: No guidelines detailing recommendations for the selection and treatment of patients with synchronous multiple primary lung cancer have been published. We report on a single-institution experience with synchronous multiple primary lung cancer, with emphasis on long-term survival. Methods: We performed a retrospective study of 125 consecutive patients with synchronous multiple primary lung cancer who underwent operation between 1985 and 2006. Various treatment strategies were applied, including perioperative therapy. Potential prognosticators were submitted to univariate and multivariate analyses. Results: Tumors were bilateral (n = 34) or ipsilateral (n = 91). Optimal surgical treatment (complete anatomic resection with radical lymphadenectomy) was possible in 65.6% of the cases. pN0 disease was present in 32.3% of the patients; 30-day and 90-day mortality rates were 4.5% and 11%, respectively. Two- and 5-year overall survivals were 61.6% and 34%, respectively, with a median survival of 35 months. On univariate analysis, smoking status, high Charlson index, low forced expiratory volume in 1 second, occurrence of postoperative complications, and performance of a pneumonectomy affected the overall survival adversely. Conversely, bilateral disease, location in the same lobe, and pN0 disease were favorable prognosticators. On multivariate analysis, low forced expiratory volume in 1 second, nonoptimal surgical treatment, and performance of a pneumonectomy were independent predictors of poor long-term survival, whereas female sex, younger age, asymptomatic disease, pN0 status, and performance of an adjuvant treatment affected the survival favorably. Conclusions: Provided there is an appropriate selection process, patients with synchronous multiple primary lung cancer are expected to benefit from surgery. Optimal surgery should be performed, but pneumonectomy should be avoided whenever possible. Adjuvant treatment is suggested to provide an added survival advantage. [Copyright &y& Elsevier]

Objective: We sought to determine quality of life impairment in hidradenitis suppurativa. Methods: Questionnaires were administered to 61 patients. Results: Quality of life impact in hidradenitis was much greater than that of several other dermatologic conditions. Limitation: This hospital-based population may not be representative. Conclusion: Hidradenitis is one of the most distressing conditions observed in dermatology. [Copyright &y& Elsevier]

Objective: The objective of the study was to evaluate the intra- and interobserver agreement among obstetric experts in court regarding the retrospective review of abnormal fetal heart rate tracings and obstetrical management of patients with abnormal fetal heart rate during labor.Study Design: A total of 22 French obstetric experts in court reviewed 30 cases of term deliveries of singleton pregnancies diagnosed with at least 1 hour of abnormal fetal heart rate, including 10 cases with adverse neonatal outcome. The experts reviewed all cases twice within a 3-month interval, with the first review being blinded to neonatal outcome. For each case reviewed, the experts were provided with the obstetric data and copies of the complete fetal heart rate recording and the partogram. The experts were asked to classify the abnormal fetal heart rate tracing and to express whether they agreed with the obstetrical management performed. When they disagreed, the experts were asked whether they concluded that an error had been made and whether they considered the obstetrical management as the cause of cerebral palsy in children if any.Results: Compared with blinded review, the experts were significantly more likely to agree with the obstetric management performed (P < .001) and with the mode of delivery (P < .001) when informed about the neonatal outcome and were less likely to conclude that an error had been made (P < .001) or to establish a link with potential cerebral palsy (P = .003). The experts' intraobserver agreement for the review of abnormal fetal heart rate tracing and obstetrical management were both mediocre (kappa = 0.46-0.51 and kappa = 0.48-0.53, respectively). The interobserver agreement for the review of abnormal fetal heart rate tracing was low and was not improved by knowledge of the neonatal outcome (kappa = 0.11-0.18). The interobserver agreement for the interpretation of obstetrical management was also low (kappa = 0.08-0.19) but appeared to be improved by knowledge of the neonatal outcome (kappa = 0.15-0.32).Conclusion: The intra- and interobserver agreement among obstetric experts in court for the review of abnormal fetal heart rate tracing and the appropriateness of obstetrical care is poor, suggesting a lack of objectivity of obstetrical expertise as currently performed in court. [ABSTRACT FROM AUTHOR]

Objective: We sought to evaluate the efficacy of maternal posturing during labor on the prevention of persistent occiput posterior (OP) position. Study Design: We conducted a randomized trial including 220 patients in labor with a single fetus in documented OP position. Main outcome was the proportion of anterior rotation from OP position. Results: The rates of anterior rotation were, respectively, 78.2% and 76.4% in the intervention group and the control group without significant difference (P = .748). Rates of instrumental and cesarean section deliveries were not significantly different between intervention and control groups (18.2% vs 19.1%, P = .89, and 19.1% vs 17.3%, P = .73, respectively). In intervention and control groups, persistent OP position rates were significantly higher among women who had cesarean section (71.4% and 89.5%, respectively) and an instrumental delivery (25% and 33.3%, respectively) than among women who achieved spontaneous vaginal birth (5.8% and 2.8%, respectively). In multivariable analysis, body mass index and parity were found to have significant and independent impact on the probability of fetal head rotation. Conclusion: Our study failed to demonstrate any maternal or neonatal benefit to a policy of maternal posturing for the management of OP position during labor. [ABSTRACT FROM AUTHOR]

Objective To study cervix elastography measurement and its relation with pregnancy outcome. Design A two year prospective longitudinal study evaluated cervical elasticity by HI-RTE (Hitachi real-time tissue elastography) imaging during three trimesters of pregnancy. The main outcome measure was elastography index the cervical elastogram color-coded. Results Three hundred eighty seven measurements were realized among 72 pregnant women prospectively enrolled. In the first trimester, the elasticity index was significantly lower in women who subsequently had unfavorable outcome than in women who delivered at term (respectively, EI = 0.51 (±0.04) and 0.59 (±0.02); P = 0.037). The negative predictive value of posterior lip color (blue, blue-green = hard cervix) was high NPV = 83.8 95% CI [68.8–92.4] in the first trimester (SE = 64.7 95% CI [41.3–82.7]; SP = 60.8 95% CI [47.1–72.9]; VPP = 35.5 95% CI [21.1–53.1]). A first-trimester elasticity index threshold value ≤0.38 had a specificity of 98.0% and a NPV of 80.9% (Se 29.4%, PPV 83.3%). This index value, when combined with a cervical length less than or equal to 36 mm, increased the risk of adverse outcome (HR 8.87 95% CI [3.22–23.7]). Conclusions Cervical elastography index is associated with unfavorable obstetrical outcomes, independently of cervical length. The study was registered in ClinicalTrials.gov under Identifier number NCT01032564. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the impact of body mass index (BMI) and the syndrome metabolic (MS) on responses to clopidogrel or prasugrel and bleeding risk after acute coronary syndrome. The study included 1,542 consecutive patients who underwent coronary stenting (287 clopidogrel 75 mg, 868 clopidogrel 150 mg, and 387 prasugrel 10 mg). Platelet reactivity was assessed 1 month after discharge using platelet reactivity index vasodilator stimulated phosphoprotein (PRI VASP). Three hundred thirty-six patients (21.8%) were obese (BMI ≥30), and we observed higher platelet reactivity associated with higher BMI across thienopyridine regimens. Incidence of high on-treatment platelet reactivity (PRIVASP >50%) was higher in obese than nonobese patients (p <0.05 for all regimens). Conversely, incidence of low on-treatment platelet reactivity with prasugrel therapy (PRI VASP <20%) was lower in obese than nonobese patients: 13% (12 of 93) versus 33% (97 of 294); odds ratio 0.30, 95% confidence interval 0.16 to 0.58; p <0.001. Accordingly, incidence of Bleeding Academic Research Consortium bleeding complications was higher in nonobese than in obese patients: 10% (119 of 1,206) versus 6% (20 of 336); odds ratio 1.7, 95% confidence interval 1.1 to 2.8; p=0.03. This impaired response was only observed in obese patients with the MS, and obese with the MShad significantly higher platelet reactivity than other obese patients with all regimens (p <0.01). Obese patients without the MS had no significant difference in platelet reactivity compared with nonobese patients. In conclusion, the present study confirmed that BMI has a strong impact on response to clopidogrel and prasugrel with higher incidence of high on-treatment platelet reactivity, lower incidence of low on-treatment platelet reactivity, and lower bleeding complication in obese patients. However, among obese patients, the presence of the MS strongly affects response to antiplatelet agents, indicating that the metabolic status might be a better predictor of platelet inhibition than BMI. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To determine the prevalence of some major mental disorders among adolescents living in a residential group home and the distribution of these disorders by gender. Method: The participants included 183 adolescents (13–17years old) living in residential group homes of the Child Welfare System in the county of Bouches-du-Rhône (South of France). A structured psychiatric Diagnostic Interview Schedule for Children was used to assess the existence of Anxiety Disorder (AD), Major Depression (MD), Conduct Disorder (CD), Eating Disorder (ED), Enuresia (En), Psychosis Screen (PS) and Attention Deficit Hyperactivity Disorder (ADHD) among the study participants over the six-month period before the assessment was taken. The existence of Suicide Attempts (SA) during the lifetime of each child was also assessed. Results: Of the youths qualified, 48.6% as having at least one psychiatric disorder during the last six months (AD: 28.4%; CD: 15.3%; MD: 14.8%; PS: 18.6%; ADHD: 3.8%), and SA have been reported in 23% of them. Females were more affected than boys (p<0.001) with 64.9% having at least one disorder compared to 36.8% of boys; AD: 49.3% vs. 13.2%; and MD: 27.3% vs. 5.6%. Conclusion: Adolescents living in residential group homes of the Child Welfare System in France have notably high rates of mental disorder (about three times more than those of the general population of the same age), similar to the patterns found in adolescents in North America and Europe. These data are the first of their kind in France and will guide necessary changes to the child welfare system. [Copyright &y& Elsevier]

Abstract: The aim of the study is to compare the expression level of candidate genes between patients suffering from a severe major depressive episode (MDE) and controls, and also among patients during MDE evolution. After a comprehensive review of the biological data related to mood disorders, we initiated a hypothesis-driven exploration of candidate mRNAs. Using RT-qPCR, we analyzed peripheral blood mononuclear cells (PBMCs) mRNA obtained from a homogeneous population of 11 patients who suffered from severe melancholic MDE. To assess the evolution of MDE, we analyzed PBMC mRNAs that were collected on Day 1 and 8 weeks later. Data from these patient samples were analyzed in comparison to age- and sex-matched healthy controls. Among 40 candidate genes consistently transcribed in PBMCs, 10 were differentially expressed in at least one comparison. We found that variations of mRNA levels for NRG1, SORT1 and TPH1 were interesting state-dependent biological markers of the disease. We also observed that variations in other mRNA expression were associated with treatment efficacy or clinical improvement (CREB1, HDAC5, HSPA2, HTR1B, HTR2A, and SLC6A4/5HTT). Significantly, 5HTT exhibited a strong correlation with clinical score evolution. We also found a state-independent marker, IL10. Moreover, the analysis of 2 separate MDEs concerning a same patient revealed comparable results for the expression of CREB1, HSPA2, HTR1B, NRG1 and TPH1. Overall, our results indicate that PBMCs obtained at different time points during MDE progression represent a promising avenue to discover biological markers for depression. [ABSTRACT FROM AUTHOR]

• The number of octogenarians with an early-stage NSCLC almost doubled each 5-year interval of the study period. • The implementation of a dedicated geriatric pathway and the use of minimally invasive approaches were both associated with improved outcomes. • Overall survival was influenced by lower co-morbidity index, highest predicted postoperative DLCO values, and absence of diabetes mellitus. We investigated on the benefit/risk ratio of surgery in octogenarians with early-stage non-small cell lung cancer (NSCLC). From 2005–2020, 100 octogenarians were operated on for a clinical stage IA to IIA NSCLC. All patients had undergone whole body PET -scan and brain imaging. Operability was assessed according to current guidelines regarding the cardiopulmonary function. Since 2015, patients followed a dedicated geriatric evaluation pathway. Minimally invasive approaches were used in 66 patients, and a thoracotomy in 34. Clavien-Dindo grade ≥ 4 complications occurred in 15 patients within 90 days, including 7 fatalities. At multivariable analysis, the number of co-morbidities was their single independent prognosticator. Following resection, 24 patients met pathological criteria for adjuvant therapy among whom 3 (12.5 %) received platinum-based chemotherapy. Five-year survival rates were overall (OS) 47 ± 6.3 %, disease-free (DFS) 77.6 ± 5.1 %, and lung cancer-specific (CSS) 74.7 ± 6.3 %. Diabetes mellitus impaired significantly long-term outcomes in these 3 dimensions. OS was improved since the introduction of a dedicated geriatric assessment pathway (72.3 % vs. 6.4 %, P = 0.00002), and when minimally invasive techniques were used (42.3 % vs. 11.3 %; P = 0.02). CSS was improved by the performance of systematic lymphadenectomy (55.3 % vs. 26.9 %; P = 0.04). Multivariable and recursive partitioning analyses showed that a decision tree could be built to predict overall survival on the basis of diabetes mellitus, high co-morbidity index and low ppoDLCO values. The introduction of a dedicated geriatric assessment pathway to select octogenarians for lung cancer surgery was associated with OS values that are similar to outcomes in younger patients. The use of minimally invasive surgery and the performance of systematic lymphadenectomy were also associated with improved long-term survival. Octogenarians with multiple co-morbid conditions, diabetes mellitus, or low ppo DLCO values may be more appropriately treated with SBRT. [ABSTRACT FROM AUTHOR]

Atelectasis frequently occurs early on during anaesthesia in children. We hypothesised that positive expiratory pressure (PEP) generated via high-flow nasal cannula (HFNC) could prevent atelectasis in non-intubated children under general anaesthesia. The objective was to compare the volume of atelectasis present in patients treated via HFNC to that of patients treated via a face bag-mask without PEP. The outcome used for this comparison was the ratio of the atelectasis volume to the total pulmonary volume. A prospective single-centre, single-blind, randomised trial was conducted in a tertiary hospital from November 2018 through May 2019. The trial subjects were infants and children between six months and six years of age who required anaesthesia for an MRI. The children were randomised to receive sevoflurane for maintenance of anaesthesia either via a classic face bag-mask or by HFNC. The atelectasis volume was measured from thoracic MRI images. The judgement criterion was the ratio of the atelectasis volume to the lung volume. Of a trial group of 42 patients, 21 received anaesthesia via a face bag-mask and 21 via HFNC. After three patients were excluded for technical issues, the data for 39 patients were analysed. The atelectasis volume to the lung volume ratio in the HFNC group was significantly smaller than the ratio for the face bag-mask group (1.6% vs 6.8%, respectively; p = 0.002). HFNC was associated with a lower atelectasis lung ratio compared to using a face bag-mask during anaesthesia for children maintained with spontaneous ventilation. Registered on Clinicaltrials.gov: NCT 03592589 [ABSTRACT FROM AUTHOR]

Brain metastases can be effectively treated with stereotactic radiosurgery (SRS). Immune checkpoint inhibitors are now pivotal in metastatic melanoma care, but some concerns have emerged regarding the safety of their combination with radiation therapy. We present a retrospective analysis of a cohort of patients treated by anti-PD1 and SRS as a sole modality of radiation therapy (no whole brain radiation therapy at any time) in a single institution. We included patients on anti-PD1 at the time of SRS or patients who started anti-PD1 within a maximum period of 3 months following SRS and were treated at least one year before the analysis. Clinical and serial imaging data were reviewed to determine the efficacy and the rate of adverse radiation effectss of the combination. A total of 50 patients were included. SRS targeted 1, 2 to 3 and >3 brain metastases in 17, 16 and 17 patients, respectively. Two patients died before the first evaluation. Nine patients presented with an increase in peritumoral oedema, three with intracranial haemorrhage and one patient with both oedema and haemorrhage. Median follow-up was 38.89 months (interquartile range 24.43; 45.28). Median overall survival from SRS was 16.62 months with 1-, 2- and 3-year rates of 60%, 40% and 35%, respectively. Median brain-Progression Free Survival was 13.2 months with 1, 2 and 3-year rates of 62.1%, 49.7% and 49.7%, respectively. This real-world cohort of patients treated with a homogeneous strategy combining upfront stereotactic radiosurgery and anti-PD1 shows remarkable survival rates and does not reveal unexpected toxicity. • Real-word cohort of patients with a standardised strategy of treatment. • Stereotactic radiosurgery and anti-PD1 can be safely combined • This combination is effective for the treatment of melanoma brain metastases. • Outcomes are favourable with a 2-years brain-PFS rate of 50%. • Data do not suggest an increased risk of adverse radiation effects. [ABSTRACT FROM AUTHOR]

Mechanical characteristics of both the healthy ascending aorta and acute type A aortic dissection were investigated using in vitro biaxial tensile tests, in vivo measurements via transoesophageal echocardiography and histological characterisations. This combination of analysis at tissular, structural and microstructural levels highlighted the following: (i) a linear mechanical response for the dissected intimomedial flap and, conversely, nonlinear behaviour for both healthy and dissected ascending aorta; all showed anisotropy; (ii) a stiffer mechanical response in the longitudinal than in the circumferential direction for the healthy ascending aorta, consistent with the histological quantification of collagen and elastin fibre density; (iii) a link between dissection and ascending aorta stiffening, as revealed by biaxial tensile tests. This result was corroborated by in vivo measurements with stiffness index, β , and Peterson modulus, E p , higher for patients with dissection than for control patients. It was consistent with histological analysis on dissected samples showing elastin fibre dislocations, reduced elastin density and increased collagen density. To our knowledge, this is the first study to report biaxial tensile tests on the dissected intimomedial flap and in vivo stiffness measurements of acute type A dissection in humans. [ABSTRACT FROM AUTHOR]

Highlights • Umbilical cord blood transplantation (UCBT) offers high survival rates in children and young adults with acute leukemia. • Even with positive pretransplantation minimal residual disease (MRD), UCBT leads to high cure rate. • Double UCBT may have a better graft-versus-leukemia effect in patients with MRD. ABSTRACT We previously reported in a French prospective randomized study that transplantation of 2 unrelated cord blood (UCB) units instead of 1 unit does not decrease the risk of transplantation failure but may enhance alloreactivity. Here we evaluated the influence of pretransplantation minimal residual disease (MRD) on leukemia relapse and survival after single- versus double-UCB transplantation (UCBT). Among 137 children and young adults who underwent UCBT in this randomized study, 115 had available data on MRD assessment done immediately before initiation of the pretransplantation conditioning regimen. MRD was considered positive at a level of ≥10−4, which was the case of 43 out of 115 patients. Overall, the mean 3-year survival probability was 69.1 ± 4.4%, and it was not significantly influenced by the MRD level: 70.7 ± 5.4% in MRD-negative (<10−4) patients (n = 72), 71.1 ± 9.4% in MRD-positive patients with 10−4 ≤ MRD <10−3 (n = 26) and 58.8 ± 11.9% in MRD-positive patients with ≥10−3 (n = 17). In the MRD-positive group, the mean risk of relapse was significantly lower in the double-UCBT arm compared with the single-UCBT arm (10.5 ± 7.2% versus 41.7 ± 10.4%; P =.025) leading to a higher mean 3-year survival rate (82.6 ± 9.3% versus 53.6 ± 10.3%; P =.031). This difference was observed only in patients who had not received antithymocyte globulin during their conditioning regimen. In the MRD-negative group, there was no differencebetween the single- and the double-UCBT arms. We conclude that even in cases of positive pretransplantation MRD, UCBT in children and young adults with acute leukemia yields a high cure rate, and that a double-unit strategy may enhance the graft-versus-leukemia effect and survival in these patients. [ABSTRACT FROM AUTHOR]

Abstract Factors determining anti-HLA immunization are poorly understood, although anti-HLA immunization following pregnancy is well described. The HLA-G molecule has been extensively described for its implication in immunological tolerance, especially during pregnancy. Transplant studies show an association between HLA-G haplotypes and alloimmunization. Our aim was to investigate the association of HLA-G haplotypes with anti-HLA class I and II immunization in a cohort of women having experienced one or more pregnancies and with no transfusion history. Maternal blood samples (n=270) collected at delivery and formerly screened for anti-HLA antibodies, HLA-A and HLA-B antigens, were screened by NGS for HLA-G gene polymorphism. Univariate analysis further confirmed that the number of pregnancies was significantly associated with anti-HLA class I immunization, whereas no other variable remained significant after Bonferroni correction. Our results showed however that anti-HLA class II immunization was associated with the number of children whereas the HLA-G*01:01:01:04 allele was protective against this immunization. [ABSTRACT FROM AUTHOR]

Background: adrenal tumor-to-liver uptake value (Tmx:Lmx) on 18F-FDG PET/CT is an accurate and reproducible PET parameter in the distinction between benign and malignant adrenal masses. The potential impact of steroid hormone secretion on 18F-FDG uptake is still debatable. The aim of this study was to evaluate this relationship. Methods: 2010-2015: 73 patients who underwent adrenalectomy for adrenocortical tumors [49 secreting/(SA) and 24 non-secreting/(NSA)] were retrospectively included in the study. Fourteen were malignant. All patients underwent hormonal evaluation, functional and anatomical imaging, Weiss scoring and Ki 67 evaluation. Results: malignant tumors exhibit higher SUVmax than benign tumors (median 7.75 vs 3.06 respectively, p < 0.001) and Tmx:Lmx was 2.7 vs 1.17 for benign tumors, p < 0.001. Tmx:Lmx was positively correlated to Weiss score (p < 0.001). No significant difference was observed for Tmx:Lmx between SA and NSA overall (p = 0.851), regardless of the subgroup of tumors analyzed. Tmx:Lmx was not correlated to tumor size (p < 0.508) or 24 h free urinary cortisol level (p < 0.522). Conclusions: no correlation was observed between Tmx:Lmx and hormonal status, however the correlation between ratio, malignancy and Weiss score confirm the utility of 18F-FDG PET/CT for the differentiation of benign from malignant adrenal lesions, irrespective of the hormone secretory status of the tumor. 18F-FDG PET/CT is a useful biomarker in the diagnosis of adrenal tumors, regardless of the secretion status. [ABSTRACT FROM AUTHOR]

Background One of the requirements of laryngoscopy is to determine which head position will result in optimal visualization. Our hypothesis was that parameters derived from magnetic resonance imaging (MRI) can help quantify the effect of age on airway modifications due to head extension during development. Method In children undergoing planned MRI, additional sequences on the upper airways were performed: one in a near-neutral position, the other with the head extended at 35°. The axis of the face, the pharynx, the larynx, the trachea, and the line of glottic visualization were determined. The following angles were calculated: the Visu-Lar angle, formed by the line of glottic visualization and the laryngeal axis, and the Phar-Lar angle, formed by the pharyngeal and laryngeal axes. Results One hundred and fifty-five patients (1 to 222 months of age [25–145] months) were included and 54% were under general anaesthesia. Age had no effect on the variation in the Visu-Lar angle, which diminished as a function of head extension, nor on the variation in the Phar-Lar angle, which was minimal in the neutral position. During extension, anatomical axes rotated similarly, and the visualization axis rotated the most, followed by the pharyngeal and laryngeal axes. These results were not correlated with general anaesthesia. Conclusion Regardless of age, head extension diminished the Visu-Lar angle, and increased the Phar-Lar angle. This study supports that, as in adults, head extension is probably the key factor for good visualization conditions during laryngoscopy on children, but clinical data is needed to confirm this result. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify antenatal prognostic factors of neonatal outcomes in cases of fetal echogenic bowel (FEB).Study Design: A retrospective study in three tertiary referral centers including fetal echogenic bowel over a 10-year period (from January 2003 to December 2013). The echogenicity of the fetal bowel was graded from 1 to 3, according to Slotnick's definition. Associated echographic findings such as bowel dilations, gallbladder abnormalities, calcifications, extra-abdominal abnormalities, intrauterine growth restriction (IUGR) and a decrease in amniotic fluid volume, if present were also recorded. This was followed by the FEB's sonographic evolution. The sonographic evolution was considered favorable if it was stable or decreasing and unfavorable if the echogenicity of the bowel increased or if additional sonographic findings appeared. Neonates had a pediatric examination in the delivery room and upon discharge from the maternity hospital. An outcome was considered good in the case of on-term delivery of a newborn with normal clinical examination and meconium elimination.Results: Complete pregnancy outcome data were available for 409 pregnancies. 338 newborns had uneventful outcomes (82.6%). Antenatal exploration diagnosed 4 cases of aneuploidy (1 case of trisomy 13, 1 case of trisomy 18 and 2 cases of triploidies), 16 cases of congenital infections, 9 cases of cystic fibrosis and 11 cases of bowel abnormalities. After a multivariate analysis, we discovered the sonographic grade of the echogenic bowel was not a prognostic factor of neonatal outcome. The isolated fetal echogenic bowel had a 6.6-fold increase chance of uneventful outcomes (adjusted odd ratio (aOR) 6.6, 95% CI 3-14.4). Notably, favorable sonographic evolution (aOR 8.1, 95% CI 4.1-16) and late gestational age at the time of the diagnosis (aOR 1.17, 95% CI 1.07-1.27) are independent, good prognostic factors of good neonatal outcomes. None of the 180 fetuses with isolated fetal echogenic bowel and favorable sonographic evolution had adverse outcomes. Among these, 4 cases (0.98%) of aneuploïdy, 17 cases (4.2%) of congenital infections and 9 cases (2.2%) of cystic fibroses were also diagnosed. No cases of Down syndrome (DS) were reported.Conclusion: Our study shows that the grade should not be considered a prognostic factor of neonatal outcomes. Our data suggests the need to reevaluate the concept of systematic amniocentesis. Sonographic evolution of fetal bowel is an independent, strong prognostic factor for good neonatal outcomes. It also better defines the FEB prognostic. [ABSTRACT FROM AUTHOR]

Succinate dehydrogenase gene (SDHx) mutations increase susceptibility to develop pheochromocytomas/ paragangliomas (PHEOs/PGLs). In the present study, we evaluate the performance and clinical applications of ¹H high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy-based global metabolomic profiling in a large series of PHEOs/PGLs of different genetic backgrounds. Eighty-seven PHEOs/ PGLs (48 sporadic/23 SDHx/7 von Hippel-Lindau/5 REarranged during Transfection/3 neurofibromatosis type 1/1 hypoxia-inducible factor 2α), one SDHD variant of unknown significance, and two Carney triad (CTr)-related tumors were analyzed by HRMAS-NMR spectroscopy. Compared to sporadic, SDHx-related PHEOs/PGLs exhibit a specific metabolic signature characterized by increased levels of succinate (P b .0001), methionine (P = .002), glutamine (P = .002), and myoinositol (P b .0007) and decreased levels of glutamate (P b .0007), regardless of their location and catecholamine levels. Uniquely, ATP/ascorbate/glutathione was found to be associated with the secretory phenotype of PHEOs/PGLs, regardless of their genotype (P b .0007). The use of succinate as a single screening test retained excellent accuracy in distinguishing SDHx versus non-SDHx-related tumors (sensitivity/ specificity: 100/100%). Moreover, the quantification of succinate could be considered a diagnostic alternative for assessing SDHx-related mutations of unknown pathogenicity. We were also able, for the first time, to uncover an SDH-like pattern in the two CTr-related PGLs. The present study demonstrates that HRMAS-NMR provides important information for SDHx-related PHEO/PGL characterization. Besides the high succinate-low glutamate hallmark, SDHx tumors also exhibit high values of methionine, a finding consistent with the hypermethylation pattern of these tumors. We also found important levels of glutamine, suggesting that glutamine metabolism might be involved in the pathogenesis of SDHx-related PHEOs/PGLs. [ABSTRACT FROM AUTHOR]

Abstract: Aim: In metastatic melanoma (MM) there is an agreement that a fast or slow progression should influence the choice between drugs with immediate impact (BRAF-inh) or delayed (ipilimumab) activity. MM kinetics thus appears crucial for medical decision, although only estimated through surrogate markers (tumour load or lactate dehydrogenase (LDH)). Our objective was to show that 1-MM kinetics can be measured and 2- is a real prognostic factor. Method: Among all stage IV MM, we retrospectively select those with long follow-up who had two comparable total body computed tomography (CT) scans within the first 3months, and did not receive meantime any treatment with a likely impact on MM kinetics. Kinetics index (KI) was calculated from changes in total metastatic volume (ΔTMV/ΔT). Results: In 126 patients, KI of progression ranges from 0 to 24,839mm3/day. Overall survival (OS) was significantly much lower in the higher terciles of KI than in the lower ones (median OS of 459, 388 and 183days, for KI of 0–99, 100–999 and ⩾1000mm3/day, respectively). In the multivariate analysis, KI was more predictive of OS than LDH or tumour load. Conclusion: Delaying major treatments in stage IV MM for a few weeks permits a measure of KI, which is the best prognostic indicator in MM. The huge range of KI probably reflects major differences in aggressiveness that any therapeutic decision should take into account. KI could be used to assess prospectively how much the efficacy of each new MM drugs is influenced by MM initial kinetics. [Copyright &y& Elsevier]

Background: Diabetes has been identified as a risk factor for impaired clopidogrel response, and these patients might have greater benefit with new P2Y12 blockers such as prasugrel. The present study was designed to assess response to thienopyridine in diabetic patients undergoing PCI for ACS. Methods and results: 107 diabetic patients undergoing PCI for ACS were included and treated by clopidogrel 600mg loading dose and switched to prasugrel 10mg daily after PCI. Platelet reactivity was assessed by PRI VASP. High-on-treatment platelet reactivity (HTPR) was defined by PRI VASP>50% and Low-on-treatment platelet reactivity (LTPR) as PRI VASP below the 75th percentile (PRI VASP<20%). After clopidogrel, mean PRI VASP was 47±21% and 54 patients (50%) were non responders. At one month, mean PRI VASP on prasugrel 10mg daily was 31±13%, 9 patients (8%) had HTPR and 23 patients (22%) had LTPR. In multivariate analysis, factors associated with platelet reactivity were waist circumference for HTPR on clopidogrel and body weight for HTPR and LTPR on prasugrel. 10 patients (9%) suffered from BARC bleeding complications. Patients with bleeding complications had significantly lower PRI VASP values: 22±9 vs. 32±13, p=0.02 and ROC curves identified a cut-off value of VASP=28% to predict bleeding complications. Conclusion: The present study confirmed that many diabetic patients treated with clopidogrel for ACS have inadequate platelet inhibition. Switch to prasugrel is effective with acceptable safety in this specific population. We observed a significant relationship between on-treatment platelet reactivity and bleeding complications. [ABSTRACT FROM AUTHOR]

Abstract: Although hematopoietic stem cell transplantation (HSCT) offers curative potential for beta-thalassemia major (beta-TM), it is associated with a variable but significant incidence of graft rejection. We studied the French national experience for improvement over time and the potential benefit of antithymocyte globulin (ATG). Between December 1985 and December 2007, 108 patients with beta-TM underwent HSCT in 21 different French transplantation centers. The majority of patients received a matched sibling transplant (n = 96) and a busulfan- and cyclophosphamide-based conditioning regimen (n = 95), also with ATG in 57 cases. Ninety-five of the 108 patients survived, with a median follow-up of 12 years. Probabilities of 15-year survival and thalassemia-free survival after first HSCT were 86.8% and 69.4%, respectively. Graft failure occurred in 24 patients, 11 of whom underwent a second HSCT. The use of ATG was associated with a decrease in rejection rate from 35% to 10%. Thalassemia-free survival improved significantly with time, reaching 83% in the 54 patients undergoing HSCT after 1994 (median time of HSCT). In view of the increased risk of graft rejection after matched sibling HSCT, current French national guidelines recommend, for all children at risk for beta-TM, the systematic addition of ATG to the myeloablative conditioning regimen and special attention to optimize transfusion and chelation therapy in the pretransplantation period. [Copyright &y& Elsevier]

Abstract: Accurate distinction of lung cancer types has become increasingly important as recent trials have shown differential response to chemotherapy among non-small cell lung carcinoma (NSCLC) subtypes. Cytological procedures are frequently used but their diagnostic accuracy has been previously questioned. However, new endoscopic and cytological techniques might have improved cytological accuracy in comparison with prior findings. The aim of this study was to reassess cytological accuracy for diagnosis of lung cancer subtypes. A retrospective chart review of subjects who underwent fiberoptic bronchoscopy (FOB) for suspicion of lung cancer in 2007–2008, was undertaken. Reports of bronchoscopically derived cytological specimens were compared to those of histological material. Endoscopic findings and specific investigational techniques were taken into account. A total of 467 FOB with both cytological and histological diagnostic techniques were performed in 449 subjects. Patients consisted of 345 men and 104 women (median age, 65 yrs). Cytology proved malignancy in 157 patients. Cytologically diagnosed carcinomas were classified into squamous cell carcinoma (SqCC) in 56, adenocarcinoma (ADC) in 6, small cell lung carcinoma (SCLC) in 12, non-small cell lung carcinoma not otherwise specified (NSCLC-NOS) in 71, and unclassified carcinoma in 12. Cytology correlated fairly with biopsy specimens, as agreement was observed in 83% of SCLC, 100% of ADC, 74% of SqCC and 8% of NSCLC-NOS. Interestingly, 61% of cytologically identified NSCLC-NOS were classified as ADC by histology. Cytological accuracy improved in case of an endobronchial lesion, mainly for SqCC. These results indicate that cytological accuracy remains fair with regard to diagnosis of squamous and non-squamous lung cancer subtypes. Improvement of cytological accuracy is expected however with novel diagnostic strategies. [Copyright &y& Elsevier]

Abstract: Clinical and experimental studies suggest that angiogenesis is a prerequisite for solid tumour growth. Glioblastoma (GBM) and pilocytic astrocytoma (PA), both angiogenic tumours display strong contrast enhancement associated with peripheral oedema in GBM but not in PA indicating differences in vascular permeability in these two types of gliomas. Here we show that expression of adrenomedullin (AM) mRNA is induced in GBM whereas is barely detectable in PA. In situ analysis of tumour specimens undergoing neovascularisation shows that the production of AM is specifically induced in a subset of GBM cells distinguished by their immediate proximity to necrotic foci (presumably hypoxic regions), suggesting a hypoxic induction of AM expression in GBM. Vascular endothelial growth factor (VEGF) mRNA levels are increased in GBM and moderate in PA. Immunohistochemical study showed that cytoplasmic AM, VEGF and HIF-1α nuclear immunoreactivity were recorded in GBM located near large necrotic areas whereas they were not expressed by PA tumour cells. Interestingly, double fluorescence immunostaining demonstrated that 85% of AM immunoreactivity colocalised with VEGF. AM transduces its effects through calcitonin receptor-like receptor/receptor activity modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). Real-time quantitative RT-PCR showed expression of RAMP2, RAMP3 and CLR in PA and GBM, suggesting that AM may function as an autocrine/paracrine growth factor for GBM cells. These observations strongly support the concept that tumour angiogenesis is regulated by paracrine mechanisms and identify beside VEGF, AM as a potential tumour angiogenesis factor in vivo which constitutes a potential interesting molecular target in GBM treatment. [Copyright &y& Elsevier]