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Summary: Background: The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk. Methods: We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as “at increased risk of severe COVID-19” in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection–hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection–hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies. Findings: We estimated that 1·7 billion (UI 1·0–2·4) people, comprising 22% (UI 15–28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from 66% of those aged 70 years or older). We estimated that 349 million (186–787) people (4% [3–9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from

Numerous studies have shown that providing straw to pigs can reduce undesirable behaviours such as aggression, tail biting and stereotypy. The measurement of various neuromodulators can be helpful in assessing the development of positive behaviours and overall animal welfare. The oxytocin release is frequently linked to positive emotions and positive welfare. It has been suggested that oxytocin modulates the serotoninergic system. This study aims to investigate the potential effect of straw provision in pigs on peripheral levels of oxytocin and serotonin. In total, 18 mini-pigs were involved in an exploratory study conducted in two parallel groups, Enriched (n=10) and Control (n=8) groups. Pigs were divided by group and housed in pens of two individuals. Straw was provided continuously only in Enriched group and renewed each day for 2 weeks. Two blood samples were drawn from each animal 5 to 10 min before providing the straw, and 15 min after providing straw, during the 1st week, to analyse peripheral changes in oxytocin and serotonin before and after straw provision, and determine the existence of a putative short-term effect. The same procedure was carried out for Control group, without straw provision. Long-term effects of straw provision were also examined using blood samples drawn at the same hour from each animal in the 2nd and 3rd weeks. During this time, animals had the permanent possibility to explore the straw in Enriched group but not in Control group. At the end of each week, one animal-keeper completed two visual analogue scales for each mini-pig regarding the difficulty/ease to work with and handle it and its trust in humans. Results showed peripheral oxytocin increases in both groups after 2 weeks (P=0.02). Results did not demonstrate any effect of providing straw to allow exploratory behaviour on peripheral serotonin. Other results were not significant. This preliminary study explored the relationship between peripheral oxytocin and serotonin and the presence of straw that allow pigs to perform exploratory behaviour, suggesting that there was no relationship between them. Some future studies may include crossing oxytocin and serotonin with other parameters, such as behavioural measures, to obtain more information about the true state of the animal and any possible relationship with pig welfare.

Objectives: To describe characteristics and survival outcomes of patients with renal collecting duct carcinoma (RCDC)., Methods: We retrospectively analyzed data from patients treated for RCDC and included in the UroCCR database between 2007 and 2023. All tumors had a centralized pathological review by a CARARE network pathologist. Oncologic outcomes for cancer-specific survival (CSS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method., Results: A total of 29 patients with RCDC were included. The prevalence of RCDC in the UroCCR database was 0.18% (29/16133). The median age was 63 years (45-81). At diagnosis, 20 (69%) patients were symptomatic and 9 (31%) had a metastatic disease. Partial and radical nephrectomy were performed in respectively 8 (29.6%) and 19 (70.4%) cases. The median CSS were 21 months (95% CI 9.6-32) and median PFS was 7 months (95% CI 3.6-10.3). In the nonmetastatic group, the median CSS was 22 months (95% CI: 6.2-37), and median PFS was 12 months (95% CI: 0-39). Two years estimated PFS and CSS rates were respectively 29.7% and 38%. A localized disease (P = .012) and a tumor size inferior to 4 cm (P = .045) were associated with better oncological outcomes., Conclusion: RCDC is a rare cancer with poor prognosis, and no treatment has demonstrated a significant improvement in survival. Recurrences are frequent and early. Management is heterogeneous and ineffective. These outcomes reinforce the need to better understand this tumor and evaluate alternative treatments., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

In cardiovascular disease (CVD) prevention, whether antihypertensive and lipid-lowering medications are used as complements to heart-healthy diets has not been thoroughly assessed. This scoping review aimed to 1) analyze observational studies that assessed the relationship between diet and antihypertensive/lipid-lowering medication use and 2) evaluate whether medication was used as a complement to heart-healthy dietary intakes. We searched MEDLINE, Embase, Web of Science, and CINAHL through 14 January, 2023, for studies that assessed either 1) intraindividual changes in diet associated with lipid-lowering/antihypertensive medication initiation or use or 2) interindividual differences in diet between users and nonusers of these medications. A total of 17 studies were included. Of those, 3 prospectively assessed the intraindividual changes in diet associated with medication initiation or use, but none documented potential changes in diet prior to medication initiation. The 14 other studies compared dietary intakes of medication users and nonusers, most of which also relied on an incomplete assessment of the temporal dynamics between diet and medication use as they employed cross-sectional (n = 12) or repeated cross-sectional (n = 2) designs. Data from 8 studies, including 4 of the 5 studies from Europe, suggested that medication was used as a complement to heart-healthy diets, whereas data from the 9 other studies, including the 4 conducted in the United States, provided no such evidence, indicating potential between-country differences in this relationship. Finally, no studies investigated how the dynamics between diet and medication use influenced the long-term CVD risk. This scoping review suggests that the current literature on the relationship between lipid-lowering/antihypertensive medication use and diet provides an incomplete perspective on how medication may influence diet in CVD prevention. Prospective studies assessing intraindividual changes in diet associated with medication initiation and use and how these dynamics influence the CVD risk are thus needed., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: During the last century, life expectancy has doubled. As a result, senior patients with cancer are more frequently referred for possible surgery. Pancreatic surgery is a complex surgery associated with significant postoperative morbidity. Surgical decision-making in the elderly population can be difficult because outcomes in the elderly are poorly defined. Our objective is to characterize differences in mortality and morbidity for pancreatic surgery in the elderly population., Methods: A retrospective review of all patients undergoing pancreatic head surgery in our tertiary referral center from 2015 to 2021 was conducted. Analysis was performed for the entire cohort, classifying patients into three age groups: <70 years, 70-79 years, and ≥80 years. Data from these three groups were compared, including comorbidity, oncologic outcomes and postoperative complications., Results: A total of 326 patients underwent pancreatic head resection. The 90-day mortality increased from 2.9% to 5.3% to 15.4% with increasing age (p = 0,015). There were no differences among the three groups in terms of postoperative morbidity. There was no difference in disease-free survival (DFS), but overall survival was better in patients under 70 years (p = 0,046)., Conclusion: Compared to younger patients, patients over 80 years old have a higher risk of mortality despite similar postoperative morbidity., Competing Interests: Declarations of Competing Interest None., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Given the importance in prevention of lower extremity amputations (LEAs) associated with diabetes or peripheral artery disease (PAD), we sought to document the trends of primary LEA in Québec, Canada, from years 2006 to 2019., Methods: Using the Québec Integrated Chronic Disease Surveillance System, we calculated crude and age-standardized annual incidence rates of primary LEA associated with diabetes and PAD among adults ≥ 40 years (99% confidence intervals [CI]), and all-cause 1-year mortality proportion trends following a primary LEA (95% CI), stratified by minor or major as the highest level of LEA during the same hospital stay and age groups. Trends were assessed using multivariate regression models., Results: In 2019, the crude rate of primary LEA was 116.0 per 100,000 (n = 825) with 93.7 and 21.9 per 100,000 of minor (n = 665) and major (n = 160) LEA, respectively. A tendency of decrease by 8% (-15.0 to 0.4%) of age-standardized incidence of primary LEA was observed between 2006 and 2019, while the absolute number of primary LEA increased from 610 to 825 cases. Minor LEA increased by 14.2% (3.7 to 25.9%) and major LEA decreased by 49.5% (-57.1 to -40.5%). Incidence trends remained stable among the 40 to 64 years, and declined by 14.6% and 20.1% for the 65 to 79 and ≥ 80 years of age groups, respectively. Major LEA decreased in all age groups, whereas minor LEA increased by 26.2% among the patients 40 to 64 years of age only. Age-standardized 1-year mortality decreased by 35.1% (95% CI, -43.4 to -25.7%) between 2006 and 2019, with a crude 1-year mortality of 11.3% in 2019., Conclusions: The reduction of major LEA and 1-year mortality are encouraging, although increased minor LEA, especially in younger age groups, emphasizes the importance to improve preventive care further., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objective: Quality of life of people living with HIV is strongly affected by sleep problems, fatigue, pain, anxiety, and depression symptoms. This study set out to evaluate the effects of autogenic training (AT) on quality of life and symptoms within this population., Methods: A mixed method randomized controlled trial was conducted. Participants were randomly assigned to either the AT group (n = 32) or the control group (CG) (n = 31). Quality of life and symptoms were measured in both groups three times: prior to intervention (T0), immediately after intervention (T3), and three months after intervention (T6). Fourteen individual interviews were conducted., Results: Results show a significant improvement in social and mental dimensions of quality of life for the two groups at T6. They also show a significant improvement in sleep for AT participants at T3. Qualitative results are consistent with quantitative ones., Conclusion: AT seems to improve sleep quality and could improve some dimensions of quality of life and other symptoms among people living with HIV. Further studies are needed to confirm these results., Trial Registration Number: NCT01901016., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: In heart failure, specific target doses for each drug are recommended, but some patients receive suboptimal dosing, others are undertreated or remain chronically in a titration phase, despite having no apparent contraindication or intolerance. We assessed the association of different levels of adherence to guidelines with outcomes in patients with heart failure and reduced ejection fraction (HFrEF)., Methods: Medical records of patients with HFrEF followed at our heart failure (HF) clinic for at least 6 months (n = 511) were reviewed and patients categorized as: 1) optimized (25.4%); 2) in-titration (29.0%); 3) undertreated (32.7%); and 4) intolerant/contraindicated (12.9%). Risk of mortality or HF events (hospitalization, emergency visit or ambulatory administration of intravenous diuretics) within one year was assessed using Cox regression models and Kaplan-Meier curves., Results: Compared to optimized patients, those intolerant (HR: 4.60 [95%CI: 2.23-9.48]; p < 0.0001) had the highest risk of outcomes, followed by those undertreated (3.45 [1.78-6.67]; p = 0.0002) and in-titration (1.99 [0.97-4.06]; p = 0.0588). Overall predictors of outcomes included loop diuretics' use (4.54 [2.39-8.60]), undertreatment (2.38 [1.22-4.67]), intolerance/ contraindication to triple therapy (3.08 [1.47-6.42]), peripheral vascular disease (2.13 [1.29-3.50]) and NYHA class III-IV (1.89 [1.25-2.85]); all p < 0.05., Conclusion: Level of adherence to guidelines is associated with outcomes, with intolerant/contraindicated patients having the worst prognosis and those undertreated and in-titration at intermediate risk compared to those optimized. Up-titration of therapy should be attempted whenever possible, considering patients' limitations, to potentially improve outcomes., Competing Interests: Declaration of Competing Interest MJ, AF, MTG, JL, MCP, CA, MW, GG, NR have no conflicts of interest to declare. DB: Moderator-presentation by Novartis. SdD: Grants-Pfizer, AstraZeneca, Roche Molecular Science, DalCor. NB: Personal fees-AstraZeneca (2019). SL: Research-Amgen and Novartis; Presentation-Bayer, Novartis, BI, Servier; Advisory board-Novartis, BI. ML: Speaker-Novartis. EOM: Consulting Fees/Honoraria-AstraZeneca, BI, BMS/Pfizer Alliance, Novartis, Amgen, Bayer, Merck; Funded grants/clinical trials-AstraZeneca, BI, BMS/Pfizer Alliance, Novartis, Amgen, Bayer, Merck, American Regent, Abbott, Cytokinetics, Eidos, Sanofi. PG: Research funding-Medtronic, Abbott Cardiovascular; Speaker-Abbott Cardiovascular. JLR: Consultant-Novartis, Bayer, Aventis, BMS, AstraZeneca. AD: Speaker bureau/adboard-Abbott, Akcea, Alnylam, AstraZeneca, Bayer BI, Novartis, Pfizer, Servier; Research support/grants-Abbott, AstraZeneca, Bayer, Corvia, Eidos, Novartis, Pfizer, Servier., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Severely obese patients have decreased cardiorespiratory fitness (CRF) and poor functional capacity. Bariatric surgery-induced weight loss improves CRF, but the determinants of this improvement are not well known. We aimed to assess the determinants of CRF before and after bariatric surgery and the impact of an exercise training program on CRF after bariatric surgery., Methods: Fifty-eight severely obese patients (46.1 ± 6.1 kg/m 2 , 78% women) were randomly assigned to either an exercise group (n = 39) or usual care (n = 19). Exercise training was conducted from the 3rd to the 6th months after surgery. Anthropometric measurements, abdominal and mid-thigh computed tomographic scans, resting echocardiography, and maximal cardiopulmonary exercise testing was performed before bariatric surgery and 3 and 6 months after surgery., Results: Weight, fat mass, and fat-free mass were reduced significantly at 3 and 6 months, without any additive impact of exercise training in the exercise group. From 3 to 6 months, peak aerobic power (V̇O 2peak ) increased significantly (P < 0.0001) in both groups but more importantly in the exercise group (exercise group: from 18.6 ± 4.2 to 23.2 ± 5.7 mL/kg/min; control group: from 17.4 ± 2.3 to 19.7 ± 2.4 mL/kg/min; P value, group × time = 0.01). In the exercise group, determinants of absolute V̇O 2peak (L/min) were peak exercise ventilation, oxygen pulse, and heart rate reserve (r 2  = 0.92; P < 0.0001), whereas determinants of V̇O 2peak indexed to body mass (mL/kg/min) were peak exercise ventilation and early-to-late filling velocity ratio (r 2  = 0.70; P < 0.0001)., Conclusions: A 12-week supervised training program has an additive benefit on cardiorespiratory fitness for patients who undergo bariatric surgery., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Integration of chromatin immunoprecipitation-sequencing and microarray data enabled us to identify previously unreported MITF-target genes, among which the amino acid transporter SLC7A5 is also included. We reported that small interfering RNA-mediated SLC7A5 knockdown decreased pigmentation in B16F10 cells but neither affected morphology nor dendricity. Treatment with the SLC7A5 inhibitors 2-amino-2-norbornanecarboxylic acid (BCH) or JPH203 also decreased melanin synthesis in B16F10 cells. Our findings indicated that BCH was as potent as reference depigmenting agent, kojic acid, but acted through a different pathway not affecting tyrosinase activity. BCH also decreased pigmentation in human MNT1 melanoma cells or normal human melanocytes. Finally, we tested BCH on a more physiological model, using reconstructed human epidermis and confirmed a strong inhibition of pigmentation, revealing the clinical potential of SLC7A5 inhibition and positioning BCH as a depigmenting agent suitable for cosmetic or dermatological intervention in hyperpigmentation diseases., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Von Hippel-Lindau disease (VHL) is a monogenic disorder characterized by the development of tumors affecting the central nervous system, kidney, pancreas, or adrenal glands, and due to germline mutations in the VHL tumor suppressor gene. About 5% of patients with a typical VHL phenotype have no mutation detected by conventional techniques, so a postzygotic VHL mosaicism can be suspected. The aim of this study was therefore to implement a next-generation sequencing (NGS) strategy for VHL mosaic mutation detection, including an optimization of the original Personal Genome Machine design by enrichment with oligonucleotides corresponding to amplicons with insufficient depth of coverage. Two complementary strategies were developed for the confirmation of mosaic mutations identified by NGS, SNaPshot for variants present at an allelic ratio greater than 5%, and droplet digital PCR for allelic ratio above 1%. VHL mutant plasmids were generated to assess VHL mosaic mutation detection in different exons and to set up an internal quality control that could be included in each run or regularly to validate the assay. This strategy was applied to 47 patients with a suggestive or clinical VHL disease, and mosaic mutations were identified in 8.5% of patients. In conclusion, NGS technologies combined with SNaPshot or droplet digital PCR allow the detection and confirmation of mosaic mutations in a clinical laboratory setting., (Copyright © 2019 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Purpose: Constitutional epimutations are an alternative to genetic mutations in the etiology of genetic diseases. Some of these epimutations, termed secondary, correspond to the epigenetic effects of cis-acting genetic defects transmitted to the offspring following a Mendelian inheritance pattern. In Lynch syndrome, a few families with such apparently heritable MLH1 epimutations have been reported so far., Methods: We designed a long-range polymerase chain reaction next-generation sequencing strategy to screen MLH1 entire gene and applied it to 4 French families with heritable epimutations and 10 additional patients with no proven transmission of their epimutations., Results: This strategy successfully detected the insertion of an Alu element in MLH1 coding sequence in one family. Two previously unreported MLH1 variants were also identified in other epimutation carriers: a nucleotide substitution within intron 1 and a single-nucleotide deletion in the 5'-UTR. Detection of a partial MLH1 duplication in another family required multiplex ligation-dependent probe amplification technology. We demonstrated the segregation of these variants with MLH1 methylation and studied the functional consequences of these defects on transcription., Conclusion: This is the largest cohort of patients with MLH1 secondary epimutations associated with a broad spectrum of genetic defects. This study provides further insight into the complexity of molecular mechanisms leading to secondary epimutations.

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disease due to mutations in the tumor suppressor gene STK11. PJS is characterized by periorificial hyperpigmented macules (lentiginosis) and hamartomatous polyposis. Polyps can be located anywhere in the gastrointestinal tract, but are preferably observed in the small bowel (70-90%), the colon (50%) and the stomach (25%). They tend to be cancerous in a particular sequence hamartoma-dysplasia-cancer. The diagnosis is often made in the first or second decade following the appearance of lentigines or upon the occurrence of complications due to polyps (obstruction, intussusception, occult bleeding responsible for anemia). Furthermore PJS is associated with a significant increase in cancer risk (relative risk of 89% over the life according to the most recent series). Digestive cancers are the more frequent with cumulative incidences of 55% for gastro-intestinal cancer (39% for colorectal cancer, 13% for small bowel cancer and between 11 and 36% for pancreatic cancer, respectively). There is also an increased risk of non digestive cancers. In particular the risk of breast cancer is similar to that of patients carrying deleterious BRCA1 or BRCA2 mutations (cumulative incidence of 45%). Gynecological and gonadal tumors are frequent as well and can be more (adenoma malignum) or less aggressive (ovarian sex cord tumors with annular tubules and testicular tumors with calcified Sertoli cells). Finally the frequency of lung cancer is moderately increased. Recommendations for screening and management based on retrospective series in the literature have led to various strategies. The aim of this paper is to summarize the clinical and molecular diagnostic criteria of PJS as well as recommendations on screening strategies, management and monitoring.

Aims: SIRT1 and AMP-activated protein kinase (AMPK) share common activators, actions and target molecules. Previous studies have suggested that a putative SIRT1-AMPK regulatory network could act as the prime initial sensor for calorie restriction-induced adaptations in skeletal muscle-the major site of insulin-stimulated glucose disposal. Our study aimed to investigate whether a feedback loop exists between AMPK and SIRT1 in skeletal muscle and how this may be involved glucose tolerance., Main Methods: To investigate this, we used skeletal muscle-specific AMPKα1/2 knockout mice (AMPKα1/2(-/-)) fed ad libitum (AL) or a 30% calorie restricted (CR) diet and L6 rat myoblasts incubated with SIRT1 inhibitor (EX527)., Key Findings: CR-AMPKα1/2(-/-) displayed impaired glucose tolerance (*p<0.05), in association with down-regulated SIRT1 and PGC-1α expression (<300% vs. CR-WT, (±±)p<0.01). Moreover, AMPK activity was decreased following SIRT1 inhibition in L6 cells (~0.5-fold vs. control, *p<0.05)., Significance: This study demonstrates that skeletal muscle-specific AMPK deficiency impairs the beneficial effects of CR on glucose tolerance and that these effects may be dependent on reduced SIRT1 levels., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: AMP-activated protein kinase (AMPK) is an evolutionarily conserved sensor of cellular energy status that contributes to restoration of energy homeostasis by slowing down ATP-consuming pathways and activating ATP-producing pathways. Unexpectedly, in different systems, AMPK is also required for proper cell division. In the current study, we evaluated the potential effect of the AMPK catalytic subunit, AMPKα1, on hepatocyte proliferation., Methods: Hepatocyte proliferation was determined in AMPKα1 knockout and wild-type mice in vivo after two thirds partial hepatectomy, and in vitro in primary hepatocyte cultures. The activities of metabolic and cell cycle-related signaling pathways were measured., Results: After partial hepatectomy, hepatocytes proliferated rapidly, correlating with increased AMPK phosphorylation. Deletion of AMPKα1 delayed liver regeneration by impacting on G1/S transition phase. The proliferative defect of AMPKα1-deficient hepatocytes was cell autonomous, and independent of energy balance. The priming phase, lipid droplet accumulation, protein anabolic responses and growth factor activation after partial hepatectomy occurred normally in the absence of AMPKα1 activity. By contrast, mRNA and protein expression of cyclin A2, a key driver of S phase progression, were compromised in the absence of AMPK activity. Importantly, AMPKα1 controlled cyclin A2 transcription mainly through the ATF/CREB element., Conclusions: Our study highlights a novel role for AMPKα1 as a positive regulator of hepatocyte division occurring independently of energy balance., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Our purpose is to review the different mechanisms involved in the vascular response following percutaneous coronary revascularization, and their role in thrombotic complications and in restenosis. Specificities related to the various techniques of percutaneous coronary revascularization (balloon angioplasty, coronary stents, brachytherapy, drug eluting stents) are discussed.

Objectives: This study aimed at: i) stating what the routines are regarding ordering of preoperative coagulation test; ii) evaluating the impact on the use of pre-operative orders from the data obtained during the first and the second parts of the study., Study Design: Descriptive and comparative epidemiologic study., Patients and Methods: This study was performed twice, and lasted for one day each during two consecutive years (1998 and 1999). It concerned 22 private clinics in the French region 'Nord-Pas-de-Calais'. The anaesthesiologists who took part in the project had to fill out an easy and brief questionnaire concerning each patient who had been admitted to the operating area. It dealt mainly with the presence or the absence, of a preoperative laboratory screening, and with who ordered the test and which tests. The results of the first part of the study (1998) have been evaluated several times with the involved anaesthesiologists. Before repeating the study in 1999, the results were first discussed and compared to the recommendations of the experts., Results: In 1998, preoperative coagulation tests were ordered for 81% of the patients (n = 662), which in more than half the cases were ordered by an anaesthesiologists. In less than 5% of the cases, one or more abnormalities were detected out of which half were predictable because of the patients previous medical history. Only one of the patients in the study suffered from an haemorrhagical problem although he had a normal coagulation screening. A year after, the ordering of a preoperative coagulation check included 75% of the patients (n = 400), which represents a small but nonetheless significant decrease of the number of orders compared to 1998 (p < 0.05). The proportion of preoperative laboratory screening prescribed by an anaesthesiologist remained the same. There were one or more abnormalities in 1% of the screening tests that were obtained. A patient had a haemorrhagical problem while she had a normal coagulation screening., Conclusions: In this study, repeated feed-back to the writers of the preoperative orders in the time interval between the two parts of the study did not induce a noticeable decrease in the number of preoperative coagulation tests ordered. The results show the necessity of a different approach to present scientific knowledge in order to modify medical behaviour.

Objective: To analyze the current knowledge concerning xenon anaesthesia., Data Sources: References were obtained from computerized bibliographic research (Medline), recent review articles, the library of the service and personal files., Study Selection: All categories of articles on this topic have been selected., Data Extraction: Articles have been analysed for history, biophysics, pharmacology, toxicity and environmental effects and using prospect., Data Synthesis: The noble gas xenon has anaesthetic properties that have been recognized 50 years ago. Xenon is receiving renewed interest because it has many characteristics of an ideal anaesthetic. In addition to its lack of effects on cardiovascular system, xenon has a low solubility enabling faster induction of and emergence from anaesthesia than with other inhalational agents. Nevertheless, at present, the cost and arety of xenon limit its widespread use in clinical practice. The developement of closed rebreathing system that allowed recycling of xenon and therefore reducing its waste has led to a recent interest in this gas. Reducing its cost will help xenon to find its place among anaesthetic agents. An European multicentric clinical trial under submission will contribute to the discussion of the opportunity for xenon introduction in anaesthesia.

Objective: To investigate whether changes in gastric intramucosal pH (pHim) occur during major abdominal surgery, and if so, to determine the relationship between classic global indices of tissue perfusion such as mean arterial blood pressure (MAP), heart rate (HR), central venous pressure (CVP), urine flow (UF) and arterial pH (pHa)., Study Design: Prospective descriptive study., Patients: Seven ASA2 patients undergoing major abdominal surgery., Methods: After induction of anaesthesia and endotracheal intubation, a tonometer nasogastric tube was positioned in the stomach. Measurements of tonometric PCO2 (PCO2ss), end-tidal PCO2 (PETCO2), PaCO2, bicarbonates [bicarb], pHa, MAP, HR, CVP and UF were collected at baseline (HO), and one, two, three, and 24 hours (H1, H2, H3, and H24) after the beginning of surgery., Results: Haemodynamics did not significantly change during anaesthesia. During recovery HR increased and CVP decreased significantly. The pHim decreased significantly from 7.42 +/- 0.03 at H0 to 7.30 +/- 0.02 at H3. This was associated with a significant decrease in pHa (from 7.43 +/- 0.02 at H0 to 7.33 +/- 0.02 at H3) and in [bicarbo] from 22 +/- 1 mmol at H0 to 20 +/- 1 mmol at H3). The PaCO2 increased significantly from 33.5 +/- 1.5 mmHg at H0 to 39.5 +/- 2.8 at H3. On the other hand, pHimcorr (7.40- (pHa-pHim) and delta CO2 (PCO2ss-PETCO2) did not vary during anaesthesia. Postoperative organ failure did not occur in these patients., Conclusions: The pHim may decrease during anaesthesia without evidence of abnormal tissue perfusion. In order to avoid.

The case of a 34-year-old woman who experienced a biological haemostasis disorder, without clinical manifestations, is reported. The disorder was caused by a factor V inhibitor induced by a prolonged administration of antibiotics required by a postoperative biliary peritonitis. Therapeutic strategies in patients with an acquired factor V inhibitor are reviewed.

We have studied the effects of oral contraceptives on three glycoproteins, alpha-1-antitrypsin (A1AT), gamma-glutamyltransferase (GGT) and alkaline phosphatase (AP), in terms of age (20--40 years), duration of administration, and levels of estrogens. We have confirmed that oral contraceptives increase the concentration of A1AT and the activity of GGT and decrease the activity of AP, but that the modifications are less pronounced with pills containing low levels of estrogens for GGT and AP. We observed a decrease in A1AT and GGT after 2 and 5 years of treatment, respectively, but an increase in AP. Patient age seemed to have little influence on the change in AP activity and A1AT concentration but GGT activity was higher for the 25--30 year group.