[How is our practice of mastectomy? Analysis based on population data in a French department]. / Quelles évolutions dans notre pratique de la mastectomie ? Analyse à partir de données de population dans un département français.

OBJECTIVE: The objective of this research was to study the evolution of the mastectomy rate in patients with breast cancer between 1998 and 2015, based on population data from the Côte d'Or breast cancer registry of the FRANCIM network ("France cancer incidence and mortality"). METHODS: In this study on population register we included patients who had presented a primary breast cancer (invasive cancer and/or carcinoma in situ [CIS]) between 1998 and 2015 in the Côte d'Or department. We estimated the annual proportions of mastectomies, then calculated their evolution trends over this period. RESULTS: Between 1998 and 2015, 7093 patients were included. The overall proportion of mastectomies was stable at 28% and did not respond to a time trend (Sen's slope of 0.2% per year; P=0.289). There was an increase in the proportion of lobular carcinomas (slope at 0.3% per year; P <0.05), with a rising proportion of mastectomy for lobular carcinomas (slope at 0.6% per year; P<0.05) but decreasing for ductal (slope at -0.8% per year; P<0.05). The proportion of mastectomy was stable for plurifocal cancers but the proportion of plurifocal cancers increased over time (slope at 0.8% per year; P<0.05). CONCLUSION: Therefore, mastectomy remained a stable practice over the 18 years of analysis in the Côte d'Or region. However, this overall stability is the result of variations in the profiles of diagnosed cancers and surgical practices.

Comparison of postoperative complications following conventional latissimus dorsi flap versus muscle-sparing latissimus dorsi flap breast reconstruction.

INTRODUCTION: Breast reconstruction is becoming increasingly important in the management of breast cancer. Among breast reconstruction with flap, latissimus dorsi flap is the most frequent technique used in France. Lipofilling's emergence led to changes for using latissimus dorsi flap in breast reconstruction. The aim of this study was to compare postoperative complications following conventional latissimus dorsi (CLD) flap versus muscle-sparing latissimus dorsi (MSLD) flap breast reconstruction. MATERIALS AND METHODS: Data from 96 patients, who underwent CLD flap or MSLD flap breast reconstruction, were retrospectively collected from January 2018 to December 2019 in Georges-Francois Leclerc Cancer Center in France. Uni- and multivariate analyses, using a logistic regression, were performed to define operative factors and postoperative morbidity associated with surgical technique and evaluate whether MSLD flap could be associated with less postoperative outcome. RESULTS: After univariate analysis, factors significantly associated with MSLD flap were reduced surgical time (p<0.001), reducing seroma and punctures (p<0.001), postoperative complications of donor site (p=0.09), and a shorter length hospital stay (p<0.001). After multivariate analysis, a shorter length hospital stay was significantly associated with the muscle-sparing group (OR=0.47, 95% CI (0.30-0.73), p<0.001). DISCUSSION: This is the first French study comparing postoperative complications following the two techniques of latissimus dorsi flap breast reconstruction. In this study, the hospital stay was significantly decreased with MSLD flap compared with the CLD flap breast reconstruction. Both seem to be reliable methods with few complications.

Prognostic factors of overall survival for patients with FIGO stage IIIc or IVa ovarian cancer treated with neo-adjuvant chemotherapy followed by interval debulking surgery: A multicenter cohort analysis from the FRANCOGYN study group.

INTRODUCTION: The aim of this study was to identify prognostic factors of overall survival in patients with FIGO stage IIIc or IVa ovarian cancer (OC) treated by neo-adjuvant chemotherapy (NAC) followed by interval debulking surgery. MATERIALS AND METHODS: Data from 483 patients with ovarian cancer were retrospectively collected, from January 1, 2000 to December 31, 2016, from the FRANCOGYN database, regrouping data from 11 centers specialized in ovarian cancer treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analysis were performed to define prognostic factors of overall survival. RESULTS: The median overall survival was 52 after a median follow up of 30 months. After univariate analysis, factors significantly associated with decreased overall survival were; no pelvic and/or para-aortic lymphadenectomy (p = 0.002), residual disease (CC1/CC2/CC3) after surgery (p < 0.001), positive cytology after NAC (p < 0.001), omental disease after NAC (p = 0.002), no pathologic complete response (pCR) (p = 0.002). In multivariate analysis, factors significantly associated with decreased overall survival were; residual disease after surgery (HR = 1.93; CI95% (1.16-3.21), p = 0.01) and positive cytology after NAC (HR = 1.59; CI95% (1.01-2.55), p = 0.05). Patients with no residual disease after surgery had a median overall survival of 64 months versus 35 months for patients with residual disease. Patients with negative cytology after NAC had a median overall survival of 71 months versus 43 months for patients with positive cytology after NAC. CONCLUSION: In this first and largest French based retrospective study, complete cytoreductive surgery in ovarian cancer remains the main prognostic factor of overall survival.

[Comparing prediction performances of 18F-FDG PET and CGFL/Curie nomogram to predict pathologic complete response after neoadjuvant chemotherapy for HER2-positive breast cancers]. / Comparaison des performances prédictives du TEP-TDM et du nomogramme CGFL/Curie pour prédire la réponse histologique complète après chimiothérapie néo-adjuvante des cancers du sein HER2-positifs.

OBJECTIVES: The aim of this study was to compare the value of 18F-fluorodesoxyglucose positron emission tomography (18F-FDG PET/CT) with CGFL/Curie nomogram to predict a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in women with human epidermal growth factor 2 (HER2)-positive breast cancer treated by trastuzumab. METHODS: Fifty-one women with HER2-positive breast cancer treated with trastuzumab plus taxane-based NAC were retrospectively included from January 2005 to December 2015. For 18F-FDG PET/CT, the analyzed predictor was the maximum standardized uptake value of the primary tumor and axillary nodes after the first course of NAC (PET2.SUVmax). pCR was defined by no residual infiltrative tumor but in situ tumor was accepted. Accuracy of CGFL/Curie nomogram and PET2.SUVmax was evaluated measuring sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV). Combined prediction was evaluated testing predictor's associations. RESULTS: For CGFL/Curie nomogram's performances, Se, Sp, PPV and NPV were respectively: 76% (95%CI: 58-90%), 57% (95%CI: 43-66%), 55% (95%CI: 42-65), 77% (95%CI: 59-90%). For PET2.SUVmax's performances, Se, Sp, PPV and NPV were respectively: 67% (95%CI: 48-81%), 77% (95%CI: 64-97%), 67% (95%CI: 48-82%), 77% (95%CI: 64-87%). ROC curves for these predictors were similar; the areas under the curve were 0.6 (95%CI: 0.56-0.64) for PET2.SUVmax and 0.55 (95%CI: 0.50-0.59) for CGFL/Curie nomogram. Combined prediction was efficient with Se at 80%, VPN at 76%, Sp at 78% and VPP at 81%. CONCLUSIONS: CGFL/Curie nomogram and PET2.SUVmax were two efficient predictors of pCR in patients with HER2-positive breast cancer. Combined prediction has an improved accuracy.

Evaluation of sedation-related medication errors in patients on contact isolation in the intensive care unit.

BACKGROUND: Patients in intensive care units (ICUs) may be placed on contact isolation for meticillin-resistant Staphylococcus aureus (MRSA) colonization to prevent transmission. Prior studies suggest that isolated patients may receive substandard care compared with non-isolated patients. An optimal level of sedation is required to facilitate mechanical ventilation (MV) and to minimize adverse outcomes. AIM: To determine if patients on MV and isolated for MRSA colonization are at increased risk of oversedation compared with non-isolated patients. METHODS: Retrospective chart review of adult patients on MV who received an MRSA nasal polymerase chain reaction assay and sedation within 24 and 48 h of ICU admission, respectively. Endpoints included rate of inappropriate sedation, length of ICU stay, length of time on MV, and incidence of ventilator-associated complications. FINDINGS: In total, 226 patients were included (114 MRSA positive, 112 MRSA negative). Baseline demographics were similar between the groups, with the exception of ICU admission diagnosis. Fifty-six (55%) isolated patients experienced inappropriate sedation compared with 49 (50%) non-isolated patients (P=0.482). Isolated patients spent longer in the ICU (10.4 vs 6.8 days, P=0.0006), longer on MV (8.98 vs 4.81 days, P<0.001), and required tracheostomies more frequently [37 (32%) vs 14 (13%), P=0.0003] than non-isolated patients. CONCLUSIONS: Isolated patients were not at increased risk of oversedation compared with non-isolated patients. There was an association between the use of contact isolation for MRSA nares colonization and prolonged ICU stay and prolonged MV.

Dietary practices in propionic acidemia: A European survey.

BACKGROUND: The definitive dietary management of propionic acidaemia (PA) is unknown although natural protein restriction with adequate energy provision is of key importance. AIM: To describe European dietary practices in the management of patients with PA prior to the publication of the European PA guidelines. METHODS: This was a cross-sectional survey consisting of 27 questions about the dietary practices in PA patients circulated to European IMD dietitians and health professionals in 2014. RESULTS: Information on protein restricted diets of 186 PA patients from 47 centres, representing 14 European countries was collected. Total protein intake [PA precursor-free L-amino acid supplements (PFAA) and natural protein] met WHO/FAO/UNU (2007) safe protein requirements for age in 36 centres (77%). PFAA were used to supplement natural protein intake in 81% (n = 38) of centres, providing a median of 44% (14-83%) of total protein requirement. Seventy-four per cent of patients were prescribed natural protein intakes below WHO/FAO/UNU (2007) safe levels in one or more of the following age groups: 0-6 m, 7-12 m, 1-10 y, 11-16 y and > 16 y. Sixty-three per cent (n = 117) of patients were tube fed (74% gastrostomy), but only 22% received nocturnal feeds. CONCLUSIONS: There was high use of PFAA with intakes of natural protein commonly below WHO/FAO/UNU (2007) safe levels. Optimal dietary management can only be determined by longitudinal, multi-centre, prospective case controlled studies. The metabolic instability of PA and small patient cohorts in each centre ensure that this is a challenging undertaking.

Dietary practices in isovaleric acidemia: A European survey.

BACKGROUND: In Europe, dietary management of isovaleric acidemia (IVA) may vary widely. There is limited collective information about dietetic management. AIM: To describe European practice regarding the dietary management of IVA, prior to the availability of the E-IMD IVA guidelines (E-IMD 2014). METHODS: A cross-sectional questionnaire was sent to all European dietitians who were either members of the Society for the Study of Inborn Errors of Metabolism Dietitians Group (SSIEM-DG) or whom had responded to previous questionnaires on dietetic practice (n = 53). The questionnaire comprised 27 questions about the dietary management of IVA. RESULTS: Information on 140 patients with IVA from 39 centres was reported. 133 patients (38 centres) were given a protein restricted diet. Leucine-free amino acid supplements (LFAA) were routinely used to supplement protein intake in 58% of centres. The median total protein intake prescribed achieved the WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Centres that prescribed LFAA had lower natural protein intakes in most age groups except 1 to 10 y. In contrast, when centres were not using LFAA, the median natural protein intake met WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Enteral tube feeding was rarely prescribed. CONCLUSIONS: This survey demonstrates wide differences in dietary practice in the management of IVA across European centres. It provides unique dietary data collectively representing European practices in IVA which can be used as a foundation to compare dietary management changes as a consequence of the first E-IMD IVA guidelines availability.

Public Health Impact of Frailty: Role of Physical Therapists.

Frailty is an emerging and immediate public health concern given the growing aging population. The condition of frailty is characterized by a reduction in physiologic reserve, which places frail older adults at considerable risk for further functional decline, hospitalization, institutionalization, and death. Recent research suggests that frailty may be reversible, which could result in significant improvement in public health. Thus, a strong impetus exists to develop strategies for frail older adults that achieve the Triple Aim through better promotion of population health, optimization of patient experiences, and delivery of high-quality care at minimal cost. Physical therapists often treat frail older adults, yet how physical therapists can contribute to preventing or reversing frailty in healthcare settings has not been described, and may potentially influence patient outcomes and healthcare spending. Therefore, the purpose of this publication is to outline the potential role of physical therapists in achieving the Triple Aim for the frail older adult population.

[Non-metastatic triple-negative breast cancer in 2016: Definitions and management]. / Tumeurs localisées du sein triple négatives en 2016 : définitions et prise en charge.

Triple-negative breast cancer (TN), as defined by the triple negativity in immunohistochemistry: the absence of estrogen receptor, progesterone receptor and the absence of overexpression or amplification of HER2, corresponds to 15 % of invasive breast cancers. This is a very heterogeneous group of tumors both at the genomic and transcriptomic level and at morphological, clinical and prognostic level. Although there are some good prognosis forms, the majority of TN tumors is characterized by a poor prognosis with a greater frequency of visceral metastases and a maximum risk of relapse in the first two years after diagnosis. Systemic adjuvant treatment with chemotherapy is almost always indicated. The surgical treatment and radiotherapy treatment should be comparable to the other subtypes and obey the same rules of oncologic surgery. TN tumors are not associated with a higher risk of locoregional relapse after conservative treatment and adjuvant radiotherapy. Optimization of systemic therapies is currently and for the last decade a challenge. A number of targeted therapies and efficiency biomarkers identification of these targeted therapies is essential to allow significant progress in optimizing systemic therapy for these tumors.

[Assessment of sentinel lymph node biopsy in patients receiving neoadjuvant chemotherapy in breast cancer: before or after?]. / Peut-on proposer un prélèvement du ganglion sentinelle en cas de chimiothérapie néoadjuvante dans les cancers du sein et à quel moment ?

The main goal of preoperative chemotherapy is to reduce the size of the tumor and allow conservative treatment. Neoadjuvant treatment can affect axillary status with a downstaging in one third of the cases. For these patients, the benefit of axillary node dissection is questioned and the sentinel node biopsy (SLNB) seems to be a relevant option. However, the timing of performing SLNB is still debated especially for clinical negative patients with negative axillary ultrasound before preoperative chemotherapy. For axillary positive nodes proved by biopsy/cytology before preoperative chemotherapy, SLNB can be an option if there is a good clinical and radiological response.

Evaluation of axillary involvement by ultrasound-guided lymph node biopsy: A prospective study.

OBJECTIVES: The primary aim of this prospective study was to evaluate the accuracy of pre-operative ultrasound (US) alone and associated with a fine needle aspiration cytology (FNAC) or a core needle biopsy (CNB) in the diagnosis of axillary node involvement in patient with breast cancer. The secondary study objective was to determine if this US±FNAC or CNB can lead to the adequate axillary surgery in cN0 and cN1 patient. METHODS: A total of 121 consecutive women with stage cT1 to cT2, cN0/cN1, invasive breast cancer were prospectively identified at our institution between February 2, 2013 and August 30, 2013. The sensitivity, specificity, VPP, NPV were calculated, with confidence intervals, using the definitive histological result of the sentinel node biopsy (SLNB) or axillary lymph node dissection (ALND) as the baseline. RESULTS: Twenty-seven CNB and 2 FNAC were performed. For the whole series, the sensitivity and the specificity of US alone were 48.7% [36-59%] and 89% [83-94%]. For US±FNAC or CNB, the sensitivity and the specificity were 35.9% [26-38%] and 98.8% [94-100%]. Seven women with cN1 clinical examination had SLNB, which permit to decrease the number of ALND of 16.3%. It would have avoided unnecessary SLNB, prompting immediate ALND in 9 patients with cN0 axillae, which means a reduction of SLNB of 8.6%. US±FNAC or CNB lead to the adequate surgery in 72.7% of cases. CONCLUSION: US±CNB or FNAC is also a relatively efficient and safe test and should be considered routinely. It allowed triaging patients to the well axillary surgery (SLNB or ALND).

Practices in prescribing protein substitutes for PKU in Europe: No uniformity of approach.

BACKGROUND: There appears little consensus concerning protein requirements in phenylketonuria (PKU). METHODS: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. RESULTS: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n=24 centres) (infants <1 year, >2-3g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n=10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n=4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n=25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). CONCLUSIONS: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.

Surgical Duration Estimation via Data Mining and Predictive Modeling: A Case Study.

Operating rooms (ORs) are one of the most expensive and profitable resources within a hospital system. OR managers strive to utilize these resources in the best possible manner. Traditionally, surgery durations are estimated using a moving average adjusted by the scheduler (adjusted system prediction or ASP). Other methods based on distributions, regression and data mining have also been proposed. To overcome difficulties with numerous procedure types and lack of sufficient sample size, and avoid distributional assumptions, the main objective is to develop a hybrid method of duration prediction and demonstrate using a case study.

Estrogen or raloxifene during postmenopausal weight loss: adiposity and cardiometabolic outcomes.

OBJECTIVE: Estrogen-based hormone therapy (HT) attenuates abdominal fat gain after menopause, but whether HT improves abdominal fat loss during weight loss is unknown. It was hypothesized that HT or a selective estrogen receptor modulator (raloxifene) would augment reductions in abdominal visceral fat during weight loss when compared to placebo, potentially increasing improvements in glucose tolerance and lipid profile. METHODS: Healthy postmenopausal women (n = 119; age 50-70 yr) underwent a 6-month weight-loss (primarily exercise) intervention with randomization to raloxifene (60 mg/d), HT (conjugated estrogens, 0.625 mg/d), or placebo. Outcomes were change in total and abdominal (visceral and subcutaneous) fat mass, lipid profile, and fasting and post-challenge glucose and insulin. RESULTS: Neither HT nor raloxifene augmented loss of total or abdominal fat mass during exercise-induced weight loss when compared with placebo. Weight loss-induced improvements in risk factors were similar among the three groups, except for a greater reduction in fasted glucose in the HT group (difference in change [95%CI] from placebo; -0.40 [-0.76, -0.05]) and greater reductions in LDL (-0.36 [-0.63, -0.09]) and increases in HDL (0.15 [0.07, 0.24]) in both treatment groups. CONCLUSIONS: Postmenopausal HT and raloxifene did not increase abdominal fat loss during weight loss, but did improve some cardiometabolic outcomes.

Dietary practices in pyridoxine non-responsive homocystinuria: a European survey.

BACKGROUND: Within Europe, the management of pyridoxine (B6) non-responsive homocystinuria (HCU) may vary but there is limited knowledge about treatment practice. AIM: A comparison of dietetic management practices of patients with B6 non-responsive HCU in European centres. METHODS: A cross-sectional audit by questionnaire was completed by 29 inherited metabolic disorder (IMD) centres: (14 UK, 5 Germany, 3 Netherlands, 2 Switzerland, 2 Portugal, 1 France, 1 Norway, 1 Belgium). RESULTS: 181 patients (73% >16 years of age) with HCU were identified. The majority (66%; n=119) were on dietary treatment (1-10 years, 90%; 11-16 years, 82%; and >16 years, 58%) with or without betaine and 34% (n=62) were on betaine alone. The median natural protein intake (g/day) on diet only was, by age: 1-10 years, 12 g; 11-16 years, 11 g; and >16 years, 45 g. With diet and betaine, median natural protein intake (g/day) by age was: 1-10 years, 13 g; 11-16 years, 20 g; and >16 years, 38 g. Fifty-two percent (n=15) of centres allocated natural protein by calculating methionine rather than a protein exchange system. A methionine-free l-amino acid supplement was prescribed for 86% of diet treated patients. Fifty-two percent of centres recommended cystine supplements for low plasma concentrations. Target treatment concentrations for homocystine/homocysteine (free/total) and frequency of biochemical monitoring varied. CONCLUSION: In B6 non-responsive HCU the prescription of dietary restriction by IMD centres declined with age, potentially associated with poor adherence in older patients. Inconsistencies in biochemical monitoring and treatment indicate the need for international consensus guidelines.

Dietary management of urea cycle disorders: European practice.

BACKGROUND: There is no published data comparing dietary management of urea cycle disorders (UCD) in different countries. METHODS: Cross-sectional data from 41 European Inherited Metabolic Disorder (IMD) centres (17 UK, 6 France, 5 Germany, 4 Belgium, 4 Portugal, 2 Netherlands, 1 Denmark, 1 Italy, 1 Sweden) was collected by questionnaire describing management of patients with UCD on prescribed protein restricted diets. RESULTS: Data for 464 patients: N-acetylglutamate synthase (NAGS) deficiency, n=10; carbamoyl phosphate synthetase (CPS1) deficiency, n=29; ornithine transcarbamoylase (OTC) deficiency, n=214; citrullinaemia, n=108; argininosuccinic aciduria (ASA), n=80; arginase deficiency, n=23 was reported. The majority of patients (70%; n=327) were aged 0-16y and 30% (n=137) >16y. Prescribed median protein intake/kg body weight decreased with age with little variation between disorders. The UK tended to give more total protein than other European countries particularly in infancy. Supplements of essential amino acids (EAA) were prescribed for 38% [n=174] of the patients overall, but were given more commonly in arginase deficiency (74%), CPS (48%) and citrullinaemia (46%). Patients in Germany (64%), Portugal (67%) and Sweden (100%) were the most frequent users of EAA. Only 18% [n=84] of patients were prescribed tube feeds, most commonly for CPS (41%); and 21% [n=97] were prescribed oral energy supplements. CONCLUSIONS: Dietary treatment for UCD varies significantly between different conditions, and between and within European IMD centres. Further studies examining the outcome of treatment compared with the type of dietary therapy and nutritional support received are required.

Dietary management of urea cycle disorders: UK practice.

BACKGROUND: There is no published data describing UK dietary management of urea cycle disorders (UCD). The present study describes dietary practices in UK inherited metabolic disorder (IMD) centres. METHODS: Cross-sectional data from 16 IMD centres were collected by a questionnaire describing the management of UCD patients on prescribed protein-restricted diets. RESULTS: One hundred and seventy-five patients [N-acetylglutamate synthase deficiency, n = 3; carbamoyl phosphate synthase deficiency (CPS), n = 8; ornithine transcarbamoylase deficiency (OTC), n = 75; citrullinaemia, n = 41; argininosuccinic aciduria (ASA), n = 36; arginase deficiency, n = 12] were reported; 70% (n = 123) aged 0-16 years; 30% (n = 52) >16 years. Prescribed median protein intake decreased with age (0-6 months: 2 g kg(-1) day(-1); 7-12 months: 1.6 g kg(-1) day(-1); 1-10 years: 1.3 g kg(-1) day(-1); 11-16 years: 0.9 g kg(-1) day(-1) and >16 years: 0.8 g kg(-1) day(-1)) with little variation between disorders. Adult protein prescription ranged 0.4-1.2 g kg(-1) day(-1) (40-60 g day(-1)). In the previous 2 years, 30% (n = 53) were given essential amino acid supplements (EAAs) (CPS, n = 2; OTC, n = 20; citrullinaemia, n = 15; ASA, n = 7; arginase deficiency, n = 9). EAAs were prescribed for low plasma quantitative essential amino acids (n = 13 centres); inadequate natural protein intake (n = 11) and poor metabolic control (n = 9). From diagnosis, one centre prescribed EAAs for all patients and one centre for severe defects only. Only 3% (n = 6) were given branch chain amino acid supplements. Enteral feeding tubes were used by 25% (n = 44) for feeds and 3% (n = 6) for medications. Oral energy supplements were prescribed in 17% (n = 30) of cases. CONCLUSIONS: In the UK, protein restriction based on World Health Organization 'safe intakes of protein', is the principle dietary treatment for UCD. EAA supplements are prescribed mainly on clinical need. Multicentre collaborative research is required to define optimal dietary treatments.

2D 1H and 13C NMR conformational studies of thienopyridines and carboline biarylic compounds.

In this paper, we report on conformational studies of biarylic compounds, as prepared through the well-known aza-Wittig methodology. The conformational studies were mainly realized by bidimensional (2D) nuclear magnetic resonance spectroscopy (NMR) and NOESY experiments. The conformational behavior showed that these biarylic compounds display an orthogonal symmetry and adopt a characteristic arrangement around the pivotal bond. Molecular modeling calculations were performed to support structure conformations.

(1)H, (13)C NMR and X-ray crystallographic studies of highly polyhalogenated derivatives of costunolide lactone.

The costunolide lactone, a sesquiterpene compound isolated from Zaluzania triiloba species, reacted with several dihalocarbene sources produced by trihaloform-NaOH under successive phase transfer reactions yielding mono-, bis- and tris-dihalocyclopropane adducts. The structures, as well as the configurational assignments of the different derivatives, were established by (1)H and (13)C NMR spectroscopy and assisted by X-ray crystallographic and molecular modelling studies. The specific shielding of protons in the neighbourhood of different halogens on the cyclopropane moieties was correlated to the pseudocontact interactions.

Lower-body adiposity and metabolic protection in postmenopausal women.

CONTEXT: It has been suggested that the propensity to store fat in the gluteal-femoral region may be cardioprotective. OBJECTIVE: The primary aim of this study was to test whether the favorable associations of leg fat with risk factors for cardiovascular disease persist after controlling for the highly unfavorable effects of abdominal (visceral or sc) adiposity in postmenopausal women. STUDY PARTICIPANTS: The study included 95 postmenopausal women [age, 60 +/- 8 yr (mean +/- SD)]. MAIN OUTCOMES: Whole-body and regional fat distribution was measured using dual-energy x-ray absorptiometry and abdominal computed tomography. Markers of insulin resistance and dyslipidemia were determined from oral glucose tolerance tests and fasted lipid and lipoprotein measurements, respectively. Primary outcomes were: fasting insulin (INS0), area under the insulin curve (INS(AUC)), product of the oral glucose tolerance test insulin and glucose AUC (INS(AUC) - GLU(AUC)), serum triglycerides (TG), and high-density lipoprotein (HDL) cholesterol. RESULTS: Controlling for trunk fat revealed a favorable effect of leg fat on INS0, INS(AUC), INS(AUC) x GLU(AUC), TG, and HDL. However, after controlling for either visceral or sc abdominal adiposity, TG was the only risk factor for which the favorable effect of leg fat persisted. CONCLUSIONS: The lack of an association between leg fat and most of the risk factors, after adjusting for abdominal visceral or sc fat, suggests an overriding deleterious influence of abdominal adiposity on cardiovascular risk. Nevertheless, our finding that regional adipose tissue depots have apparent independent and opposing effects on serum TG supports the need for further research into the physiological mechanisms governing these effects.