Effect of intra-operative intravenous lidocaine on opioid consumption after bariatric surgery: a prospective, randomised, blinded, placebo-controlled study.

Peri-operative lidocaine infusion warrants investigation in bariatric surgery because obese patients present different physiological and pharmacological risks. This single-centre, prospective, randomised double-blind placebo-controlled study enrolled obese patients scheduled for laparoscopic bariatric surgery using an enhanced recovery protocol. Patients received either lidocaine (bolus of 1.5 mg.kg-1 , then a continuous infusion of 2 mg.kg-1 .h-1 until the end of the surgery, then 1 mg.kg-1 .h-1 for 1 h in the recovery area) or identical volumes and rates of 0.9% saline. The primary outcome was the consumption of the equivalent of oxycodone consumption over the first 3 postoperative days. Secondary outcomes were: postoperative pain; incidence of nausea and vomiting; bowel function recovery; and lengths of stay in the recovery area and in hospital. Plasma concentrations of lidocaine were measured. On the 178 patients recruited, data were analysed from 176. The median (IQR [range]) equivalent intravenous oxycodone consumption was 3.3 mg (0.0-6.0 [0.0-14.5]) and 5.0 mg (3.3-7.0 [3.3-20.0]) in the lidocaine and saline groups, respectively (difference between medians (95%CI): 1.7 (0.6-3.4) mg; p = 0.004). Length of stay in the recovery area, postoperative pain, nausea and vomiting, day of recovery of bowel function, and length of stay in hospital were not different between groups. Mean (SD) lidocaine plasma concentrations were 2.44 (0.70) µg.ml-1 and 1.77 (0.51) µg.ml-1 at the end of surgery and 1 hour after the end of infusion, respectively. Lidocaine infusion during bariatric surgery resulted in a clinically non-relevant difference in postoperative oxycodone consumption.

First evidence of the presence of genomic islands in Escherichia coli P4, a mammary pathogen frequently used to induce experimental mastitis.

Mastitis pathogens belonging to Escherichia coli species are often considered as environmental opportunistic pathogens that invade the udder and are rapidly killed by the immune system of cows. However, several studies have reported that some of these strains are able to persist in the udder for prolonged periods or to adhere and invade mammary epithelial cells, suggesting that they might possess some specific properties or genes that could be involved in their capacity to provoke mastitis. The aim of this work was to search for such specific genes in the E. coli strain P4, which was isolated from a case of severe mastitis and is often used to induce experimental mastitis. We established that this strain belongs to phylogenetic group A of the E. coli species, and that its core genome is very similar to that of the commensal nonpathogenic strain E. coli K-12 MG1655. Seventeen transfer RNA loci, known to be frequently associated with genomic islands, were screened and an altered structure was detected for 7 of them. The partial characterization of 5 of these loci (asnT, leuX, pheV, serU, and thrW) and the complete characterization of 1 (argW) revealed the presence of genomic islands that differ from those already described in pathogenic or nonpathogenic E. coli strains.

Short communication: Effect of subclinical mastitis on proteolysis in ovine milk.

The aim of this work was to evaluate the effect of intramammary infection (IMI) on the endogenous proteolysis of milk. Four control checks were carried out in the half-udder milk of 10 ewes that acquired unilateral subclinical mastitis. Two of these checks were conducted before the infection was established and 2 after. Ten healthy ewes were tested as a control group. The presence of a subclinical IMI involved an increase of the products of casein hydrolysis, the proteose-peptone (p-p) fraction and minor (m) caseins, and a decrease of ß-casein. As a result, a significant increase in the proteolysis index (PI), calculated as the ratio of m-casein to the sum of caseins (α + ß + κ), took place. α-Casein and κ-casein were not significantly affected by IMI. Correlations confirmed the scenario: log(10) of somatic cell count (SCC) was positively correlated with p-p content and negatively with ß-casein, whereas log(10) SCC was not correlated with α-casein or κ-casein. On the other hand, p-p content was positively correlated with m-casein and PI and negatively with ß-casein, but no correlation was detected between p-p content and α- or κ-casein. Furthermore, between casein fractions, m-casein was only significantly correlated with ß-casein. These results suggest that use of indices of proteolysis of caseins such as p-p, m-casein, and PI, could be applied together with SCC to evaluate the cheese-making quality of milk.

Bariatric revisional surgery: What are the challenges for the patient and the practitioner?

Bariatric revisional surgery represents an important new issue for obese patients because of the considerable rate of failure and complications following bariatric surgery. As the frequency of bariatric procedures increases, so too does the incidence of revisional surgery, which has become becoming increasingly important. The surgeon must know the indications and the results of the various revisional procedures in order to best guide the therapeutic decision. The current challenge is to correctly select the patients for revisional surgery and to choose the appropriate procedure in each case. Multidisciplinary management is essential to patient re-assessment and to prepare the patient for a re- intervention. The objective of this update, based on data from all the most recent studies concerning revisional surgery, is to guide the surgeon in the choice of the revisional procedure, depending on patient characteristics, co-morbidities, the previously performed procedure, the type of failure or complication observed, but also on the surgeon's own habits and the center's expertise. The collected results show that revisional surgery is difficult, with higher complication rates and weight-loss results that are often lower than those of first-intent surgery. For these reasons, patient selection must be rigorous and multidisciplinary and the management in expert centers of these difficult situations must be encouraged.

Early continuous glucose monitoring for predicting remission of type 2 diabetes 1 year after bariatric surgery.

BACKGROUND: Bariatric surgery in obese subjects can result in remission of type 2 diabetes (T2D) at a distant time post-surgery. The aim of our observational prospective single-centre study was to examine glycaemic patterns in adult T2D candidates for bariatric surgery using a continuous glucose monitoring (CGM) sensor for 14 days after surgery to search for indicators predictive of T2D remission 1 year later. METHODS: Patients underwent CGM preoperatively and for 14 days postoperatively. Thereafter, body weight and glycated haemoglobin (HbA1c) levels were monitored at 3, 6 and 12 months after surgery. RESULTS: A total of 31 patients (mean age 47±2 years) were analyzed. After surgery, mean interstitial glucose levels fell rapidly from 157±31mg/dL preoperatively to 109±35mg/dL postoperatively (P<0.001), reaching nadir levels from day 3 after surgery. Successful bariatric surgery (loss of excess weight ≥50%) was observed in 28 (90%) patients, and diabetes remission (HbA1c≤6% with no antidiabetic treatment) 1 year after surgery was noted in 21 (68%) patients. CGM for 14 days post-surgery allowed prediction of diabetes remission 1 year after surgery: time spent above range <14% and standard deviation (SD) of glucose levels <33mg/dL were both strong predictors of T2D remission. Indeed, the association of these two criteria predicted diabetes remission with a 100% positive predictive value, 81% sensitivity and 100% specificity and, when combined with the advanced Diabetes Remission (Ad-DiaRem) score, further increased predictive accuracy. CONCLUSION: The use of 14-day postoperative CGM recordings together with presurgical clinical scores can help to predict diabetes remission 1 year after bariatric surgery.

Short communication: can the mammopathogenic Escherichia coli P4 strain have a direct role on the caseinolysis of milk observed during bovine mastitis?

During bacterial bovine mastitis, the quality of milk is altered because of caseinolysis. Endogenous potential actors in milk responsible for this caseinolysis have been well studied, unlike the exogenous bacterial ones. The aim of this study was to evaluate the direct role in caseinolysis of a mammopathogenic strain, Escherichia coli P4. Secretion of at least 4 extracellular bacterial caseinolytic enzymes was highlighted by zymography, in 3 different growth media, and at each bacterial growth state, suggesting that their expression was constitutive. Different experimental conditions to evaluate caseinolytic potential did not show any significant caseinolytic activity of E. coli P4 and of the 4 extracellular proteases detected, suggesting that the high caseinolysis observed during E. coli bovine mastitis does result from endogenous milk actors.

Drinking behavior of lactating dairy cows and prediction of their water intake.

The water intake of 41 lactating dairy cows managed according to current dairy farm practices was individually and continuously monitored to 1) investigate drinking behavior and 2) determine factors affecting water intake. The cows were housed in a free-stall barn and fed once daily with a corn silage and concentrate-based total mixed ration (48% dry matter content; 20.6 +/- 3.3 kg/d of dry matter intake). Cows were milked twice daily, with a yield of 26.5 +/- 5.9 kg/d. The daily free water intake (FWI) was 83.6 +/- 17.1 L, achieved during 7.3 +/- 2.8 drinking bouts. The drinking bout water intake was 12.9 +/- 5.0 L. Almost three-fourths of the FWI occurred during working hours (0600 to 1900 h). Consumption peaks corresponded to feeding and milking times. More than one quarter of the daily FWI was met during the 2 h after each milking. About 75% of the present cows visited the watering point at least once during the 2 h after the evening milking. It is probable that drinking behavior evolved with lactation, but further studies are required to identify the relationship between lactation stage and drinking behavior. The most relevant factors affecting the daily FWI of lactating cows were best combined according to the following predictive equation: (R(2) = 0.45; n = 41 cows, n = 1,837): FWI, L/d = 1.53 x dry matter intake (kg/d) + 1.33 x milk yield (kg/d) + 0.89 x dry matter content (%) + 0.57 x minimum temperature ( degrees C) - 0.30 x rainfall (mm/d) - 25.65. The results obtained using these equations were in agreement with the equations developed by other researchers.

[Using administrative data to assess the impact of length of stay on readmissions: study of two procedures in surgery and obstetrics]. / Lien entre durée de séjour et réadmissions en chirurgie et en obstétrique: étude de deux procédures à partir des données du PMSI.

BACKGROUND: The prospective payment system for the French short-stay hospitals creates a financial incentive to reduce length of stay. The potential impact of the resulting decrease in length of stay on the quality of healthcare is unknown. Readmission rates are valid outcome indicators for some clinical procedures. METHODS: Retrospective study of the association between length of stay and unplanned readmissions related to the initial stay, for two procedures: cholecystectomy and vaginal delivery. DATA: Administrative diagnosis-related groups database of "Assistance publique-Hôpitaux de Paris", a large teaching hospital, for years 2002 to 2005. RESULTS: The risk of readmission according to length of stay, taking age, sex, comorbidity, hospital and year of admission into account, followed a J-shaped curve for both procedures. The probability of readmission was higher for very short stays, with odds ratios and 95% confidence intervals of 6.03 [2.67-13.59] for cholecystectomies (1- versus 3-night stays), and of 1.74 [1.05-2.91] for vaginal deliveries (2- versus 3-night stays). CONCLUSION: For both procedures, the shortest lengths of stay are associated with a higher readmission probability. Suitable indicators derived from administrative databases would enable monitoring of the association between length of stay and readmissions.

[Omental infarct after a gastric by-pass]. / Infarctus épiploïque après by-pass gastrique.

The authors describe the case of a 56 year old woman 25 days status post laparoscopic gastric bypass who presented with an acute onset of severe epigastric pain with signs of inflammation and localized peritoneal irritation. Although her findings suggested a late anastomotic leak, an abdominal CT scan revealed only necrosis of the greater omentum beneath the left hepatic lobe. This finding permitted a non-surgical approach; after observation over several days, the patient's symptoms resolved completely.

Guiding the non-bariatric surgeon through complications of bariatric surgery.

Complications in bariatric surgery are varied; they are severe at times but infrequent. They may be surgical or non-surgical, and may occur early or late. The goal of this systematic review is to inform and help the attending physician, the emergency physician and the non-bariatric surgeon who may be called upon to manage surgical complications that arise after adjustable gastric band (AGB), sleeve gastrectomy (SG), or gastric bypass (GBP). Data from evidence-based medicine were extracted from the literature by a review of the Medline database and also of the most recent recommendations of the learned societies implicated. The main complications were classified for each intervention, and a distinction was made between early and late complications. Early complications after AGB include prosthetic slippage or perforation; SG can be complicated early by staple line leak or fistula, and BPG by fistula, stenosis and postoperative hemorrhage. Delayed complications of AGB include intragastric migration of the prosthesis, late prosthetic slippage and infection, while SG can be complicated by gastro-esophageal reflux, and BPG by anastomotic ulcer and internal hernia. The analysis of available data allowed us to develop decisional algorithms for the management of each of these complications.

Impact of Intragastric Balloon Before Laparoscopic Gastric Bypass on Patients with Super Obesity: a Randomized Multicenter Study.

BACKGROUND: Super obese patients are recommended to lose weight before bariatric surgery. The effect of intragastric balloon (IGB)-induced weight loss before laparoscopic gastric bypass (LGBP) has not been reported. The aim of this prospective randomized multicenter study was to compare the impact of preoperative 6-month IGB with standard medical care (SMC) in LGBP patients. METHODS: Patients with BMI >45 kg/m2 selected for LGBP were included and randomized to receive either SMC or IGB. After 6 months (M6), the IGB was removed and LGBP was performed in both groups. Postoperative follow-up period was 6 months (M12). The primary endpoint was the proportion of patients requiring ICU stay >24 h; secondary criteria were weight changes, operative time, hospitalization stay, and perioperative complications. RESULTS: Only 115 patients were included (BMI 54.3 ± 8.7 kg/m2), of which 55 underwent IGB insertion. The proportion of patients who stayed in ICU >24 h was similar in both groups (P = 0.87). At M6, weight loss was significantly greater in the IGB group than in the SMC group (P < 0.0001). Three severe complications occurred during IGB removal. Mean operative time for LGBP was similar in both groups (P = 0.49). Five patients had 1 or more surgical complications, all in the IGB group (P = 0.02). Both groups had similar hospitalization stay (P = 0.59) and weight loss at M12 (P = 0.31). CONCLUSION: IGB insertion before LGBP induced weight loss but did not improve the perioperative outcomes or affect postoperative weight loss.

[Evolution of functional autonomy in geriatric medium-term care units: a reliable performance indicator?]. / Evolution de l'autonomie fonctionnelle en soins de suite gériatriques: un indicateur de performance?

The objective of this study was to compare the evolution of the level of functional dependence of patients between the time of their hospital admission and release following treatment received in the geriatric medium-term care units, in order to propose this variable as a clinical performance indicator for this type of service. The differential score of physical dependence observed was determined for each hospital stay, and the adjusted significant functional improvement rate (SFI) was calculated for every unit. This adjusted SFI rate was then compared to the overall rate of all of the units combined. The overall SFI rates were 23% in 2004. Seven of the 49 units studied present an adjusted rate significantly inferior to the average rate of the total number of units combined. This study constitutes one of the first performance analyses in the medium-term sector, and the adjusted SFI rate seems to be a pertinent and reliable indicator within this framework.

Stenosis without stricture after sleeve gastrectomy.

Sleeve gastrectomy (SG) is an increasingly popular restrictive bariatric procedure as attested by the 5,302 procedures performed in 2009, increasing worldwide to 13,557 in 2011 and to 24,190 in 2013. Among the early complications, gastric stricture is well described with a prevalence between 0.7 and 4.0% (Dhahri et al., 2010). The patient reported here had functional stenosis without any underlying anatomic stricture. This complication is rare and is the consequence of spiral stapling resulting in a gastric tube that is twisted from the start (Iannelli et al., 2014). Twisted sleeve gastrectomy resulting from spiral stapling exposes the patient to the risk of recurrent dysphagia, which has the appearance of stenosis on upper GI series but not on fibroscopy. Conversion to RY-GBP is one solution. At six months follow-up after conversion, our patient is symptom-free, with quality of life was rated excellent (a score greater than 9 on the BAROS questionnaire).

Comparison of the pharmacokinetic profiles of three low molecular mass heparins--dalteparin, enoxaparin and nadroparin--administered subcutaneously in healthy volunteers (doses for prevention of thromboembolism).

The present trial was designed to comparatively investigate the pharmacokinetic profile and evaluate the apparent bioavailability pattern of three already marketed low molecular mass heparins (LMMHs): dalteparin (Fragmin), nadroparin (Fraxiparin), and enoxaparin (Lovenox) given by subcutaneous route. The study was carried out in 20 healthy young volunteers given, according to a cross over design, a single subcutaneous injection of the doses recommended for the prophylaxis of deep vein thrombosis (commercial preparations, prefilled syringes): dalteparin 2,500 IU (= 2,500 IU anti-Xa), nadroparin 7,500 ICU (= 3,075 IU anti-Xa), enoxaparin 20 mg (= 2,000 IU anti-Xa) and enoxaparin 40 mg (= 4,000 IU anti-Xa). Of the markers used, activated partial thromboplastin time (APTT), thrombin clotting time (TCT), Heptest, anti-thrombin (aIIa) activity and anti-Xa (aXa) activity, the most pertinent parameter (from a biodynamic viewpoint) is plasma aXa activity. We demonstrated that dalteparin, nadroparin and enoxaparin exhibit statistically significantly different pharmacokinetic and overall disposition patterns. Normalized to the same injected dose (1,000 IU aXa), the relative actual amount of plasma anti-Xa activity generated by enoxaparin is 1.48 times greater (p < 0.001) than that of nadroparin and 2.28 times greater (p < 0.001) than that of dalteparin while the plasma amount induced by nadroparin is 1.54 times greater (p < 0.001) than that of dalteparin. The apparent total body clearance of enoxaparin doses (CL/F = 16.7 +/- 5.5 and 13.8 +/- 3.2 ml/min) is significantly smaller than those of nadroparin (CL/F = 21.4 +/- 7.0 ml/min; p < 0.01) and dalteparin (CL/F = 33.3 +/- 11.8 ml/min; p < 0.001) while dalteparin apparent clearance is about 1.5-fold greater (p < 0.001) than that of nadroparin. These LMMHs also differ by their renal excretion pattern: more fragments exhibiting an anti-Xa activity are recovered in urine following enoxaparin doses (6.4 and 8.7% of the dose, respectively) than following nadroparin (3.9%) and dalteparin (3.4%) injection. These differences in the disposition profiles explain why the apparent elimination half life t1/2 values of the LMMHs compared here are different: dalteparin: 2.8 h; nadroparin: 3.7 h; and enoxaparin: 4.1 h. Whether or not these differences may contribute to explain the different safety/efficacy balance of each of these antithrombotic medications remains to be discussed and needs further studies.

Comparative bioavailability study of cefixime administered as tablets or aqueous solution.

The relative bioavailability of cefixime was studied in 24 healthy male volunteers, with each subject receiving a single 400mg dose of cefixime administered as an aqueous solution, a 400mg tablet and two 200mg tablets, in a randomised crossover sequence. Serum and urine samples were analysed using high-performance liquid chromatography. Peak cefixime levels were achieved 3 hours after administration of the solution vs 4 hours for the 2 tablet formulations; however, the extent of absorption was only slightly improved with the solution (by 14 and 7% compared with the 1 x 400 and 2 x 200mg tablets, respectively). The 400mg and 2 x 200mg tablets were found to be bioequivalent. The pharmacokinetic profile of the 400mg cefixime tablet (mean maximum plasma concentrations of 4.4 mg/L at 4 hours, area under the concentration-time curve of 34.4 mg/L.h, and apparent terminal elimination half-life of 3.7 hours) supports the clinical evaluation of a 400mg once-daily dosage regimen for cefixime.

Critical factors for pharmacokinetics of zopiclone in the elderly and in patients with liver and renal insufficiency.

Zopiclone, a new hypnotic cyclopyrrolone, undergoes extensive hepatic metabolism. The carrier of hypnotic activity is the parent compound; however, knowledge of its metabolic profile is essential for the understanding of pharmacokinetic changes in various pathophysiological conditions. In 45 healthy young volunteers, zopiclone had a Tmax of 0.5. A first-pass effect of 20% resulted in an absolute bioavailability, F, of 77%. The volume of distribution ratio Vdc/Vdt was 3.2. The plasma half-life (t1/2) was 5.1 h. A metabolic ratio of 3.7 and 4.6 was found for the two main urinary metabolites, N-oxide and N-desmethyl derivatives. No modifications of kinetics were seen after chronic treatment. In eight patients with liver insufficiency, the main changes (delayed Tmax, 3.5 h, higher plasma concentrations with an increased F of 97%, prolonged t1/2 of 8.4 h) were essentially due to a reduced hepatic metabolic clearance, as shown by a decreased metabolic ratio for the two main metabolites. In 18 patients with renal insufficiency, the only major modification was an increased bioavailability (F of 115%) probably due to a relative decrease of the Vdc. In 19 elderly subjects, the main findings were a decreased metabolic clearance, as shown by decreased metabolic ratios, and an inversion of the Vdc/Vdt ratio, evoking the changes seen in renal insufficiency. The increase in F (168%) and the age-dependent increase in plasma t1/2 (8.1 h) in the oldest subjects (over 74 years of age) can be explained by this double mechanism. On the basis of these findings, a reduction of the initial zopiclone dose from 7.5 to 3.5 mg/day is recommended for patients with severe liver insufficiency and patients over 70 years of age with liver insufficiency.

Single- and multiple-dose pharmacokinetics of riluzole in white subjects.

Riluzole is a novel neuroprotective agent that has been developed for the treatment of amyotrophic lateral sclerosis. A series of studies was undertaken to establish its pharmacokinetics on single- and multiple-dose administration in young white male volunteers. The mean absolute oral bioavailability of riluzole (50-mg tablet) was approximately 60%. Maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) values were linearly related to dose for the range studied. Cmax occurred at 1.0 hour to 1.5 hours after administration. Plasma elimination half-life appeared to be independent of dose. After repeated administration of 100 mg riluzole for 10 days, some intraindividual variability in bioavailability was seen. A high-fat meal significantly reduced the rate (tmax = 2 hours compared with 0.8 hours; Cmax = 216 ng.mL-1 compared to 387 ng.mL-1) and extent of absorption (AUC = 1,047 ng.hr.mL-1 versus 1,269 ng.hr.mL-1). With multiple-dose administration, riluzole showed dose-related absorption, although the terminal plasma half-life was prolonged slightly. Steady-state plasma concentrations were achieved within 5 days. Steady-state trough plasma concentrations were significantly higher with a 75-mg dose twice daily than with a 50-mg dose three times daily, although AUC values did not differ.

The antithrombotic activity and pharmacokinetics of enoxaparine, a low molecular weight heparin, in humans given single subcutaneous doses of 20 to 80 mg.

The pharmacokinetics of enoxaparine, a low molecular weight heparin, was randomly studied in 12 healthy male volunteers. Doses of 20, 40, 60, and 80 mg were injected subcutaneously in randomized cross-over fashion. Anti-IIa and anti-Xa activities (using amidolytic methods), and calcium thrombin time, were measured over 36 hours. The maximum Amax of the anti-IIa and anti-Xa activities appeared 3 to 4 hours after administration. The terminal half-lives of anti-IIa and anti-Xa activities were approximately 2 and 4 hours, respectively, with no significant variation between the different doses. For the anti-Xa activity, there was a highly significant positive correlation between the dose injected and individual values of Amax (r = +0.915; P less than .001) and AUC (r = +0.913; P less than .001). Enoxaparine displays a relatively small apparent volume of distribution (about 7.0 L) and its total body clearance is about 1.25 L/hr. The mean residence time ranges from 4.6 to 7.6 hours. Thus, the pharmacokinetic profile of enoxaparine is characterized by a linear relationship between dose and absorption, a relatively low clearance and long elimination half-life, and a high anti-Xa/anti-IIa ratio.

Pharmacokinetics of sparfloxacin in humans after single oral administration at doses of 200, 400, 600, and 800 mg.

The pharmacokinetics of sparfloxacin at oral doses of 200, 400, 600, and 800 mg were studied in 12 healthy volunteers in a randomized double-blind crossover study. Each dose administration was separated by a 1-week washout period. Plasma and urine samples were collected up to 120 hours postdosing, for determination of free and total (free plus glucurono-conjugated) sparfloxacin levels by high-performance liquid chromatography assay and ultraviolet detection. Mean Cmax values ranged from 705 +/- 158 to 1966 +/- 620 ng/mL for the 200 to 800 mg doses, at median tmax ranging from 4 to 5 hours. A slight decrease of sparfloxacin bioavailability with increasing dose was observed because AUC was 87% to 88% of the expected area when the dose was doubled. The elimination half-life values were constant over the dose range (with values ranging from 18 to 21 hours) as well as the renal clearance. The metabolic ratio conjugated/free drug was not modified by increasing dose.

Determination of acenocoumarol in plasma and urine by double radioisotope derivative analysis.

Acenocoumarol, to which a 14C-labeled internal standard has been added, is extracted at pH 4 into ethyl acetate-heptane (20:80 v/v), back-extracted into aqueous sodium hydroxide solution after solvent washing with a pH 7 buffer, and reextracted after acidification in the solvent mixture. It is then acetylated with 3H-acetic anhydride. The acenocoumarol acetyl derivative is separated from the metabolite derivatives by TLC, and its radioactivity is measured. The method is specific and sensitive to a concentration of 8 ng/ml.