Plantar compartment block for hallux valgus surgery: a proof-of-concept anatomic and clinical study.

BACKGROUND: Hallux valgus surgery is associated with moderate to severe postoperative pain. We hypothesized that a plantar compartment block may be a good technique for postoperative analgesia. We describe an anatomic approach to ultrasound-guided plantar compartment block and assess the clinical efficacy of the block for outpatient surgery. METHODS: The anatomic study was aimed to describe the plantar compartment, using both dissection methods and imaging, and to define a volume of local anesthetic. Patients scheduled for hallux valgus surgery with a popliteal sciatic nerve block, and combined plantar compartment and peroneal blocks were included in the clinical study. Data on attaining the criteria for rapid exit from the outpatient center, duration of sensory and analgesic block, visual analog scale (VAS) values for postoperative pain at rest and during movement, and the consumption of morphine as rescue analgesia were recorded. RESULTS: Plane-by-plane dissections and cross-sections were done in five cadaveric lower limbs. The medial calcaneal nerve divides into medial plantar and lateral plantar nerves in the upper part of the plantar compartment. These nerves were surrounded by 5 mL of colored gelatin, and 10 mL of injectates dye spread to the medial calcaneal branches. Thirty patients (26 women) were included in the clinical study. There were no failures of surgical block. Ninety per cent of patients successfully passed functional testing for ambulatory exit from the center within 5 hours (25th-75th centiles, 3.8-5.5 hours). The median duration of plantar compartment sensory block was 17.3 hours (10.5-21.5 hours), and the first request for rescue analgesic was 11.75 hours (10.5-23 hours) after surgery. The median VAS score for maximum pain reported within the 48-hour period was 2 (1-6). Twelve patients received 2.5 mg (0-5 mg) of morphine on day 1. Patients were highly satisfied and no adverse events were noted. CONCLUSIONS: This anatomic description of the ultrasound-guided plantar compartment block reported the injection area to target the medial and lateral plantar nerves with 5 mL of local anesthetic. Normal walking without assistance is attained rapidly with this regional anesthesia technique, and the time to request postoperative analgesia after hallux valgus surgery is long. TRIAL REGISTRATION NUMBER: NCT03815422.

CX3CL1/Fractalkine as a biomarker for early pregnancy prediction of preterm premature rupture of membranes.

OBJECTIVES: The objective of our study was to evaluate serum CX3CL1/Fractalkine, a monocyte/macrophage chemoattractant expressed in cytotrophoblasts and decidual cells, as a predictive biomarker for the occurrence of preterm premature rupture of membranes (PPROM). METHODS: A case-control study of 438 pregnancies including 82 PPROM cases and 64 preterm labor with intact membranes cases with blood samples collected at first trimester, second trimester and delivery was conducted. The predictive ability of CX3CL1 and maternal risk factors for the occurrence of PPROM was assessed by receiver operating characteristic curve analysis. A second, independent cohort was prospectively constituted to confirm the case-control study results. RESULTS: First trimester CX3CL1 was significantly increased in PPROM cases when compared to matched controls. Multivariate regression analysis highlighted a significant difference for CX3CL1 measured during the first trimester (p<0.001). Alone, CX3CL1 predicts PPROM with a 90 % sensitivity and a specificity around 40 %. The area under the receiver operating characteristic curve for PPROM prediction were 0.64 (95% confidence interval: 0.57-0.71) for first trimester CX3CL1, and 0.61 (95% confidence interval: 0.54-0.68) for maternal risk factors (body mass index<18.5 kg/m2, nulliparity, tobacco use and the absence of high school diploma). The combination of CX3CL1 and maternal risk factors significantly improved the area under the curve: 0.72 (95% confidence interval: 0.66-0.79) (p<0.001). The results were confirmed on a second independent cohort. CONCLUSIONS: CX3CL1 is a promising blood biomarker in the early (first trimester) prediction of PPROM.

Microbial associations for bioremediation. What does "microbial consortia" mean?

Microbial associations arise as useful tools in several biotechnological processes. Among them, bioremediation of contaminated environments usually takes advantage of these microbial associations. Despite being frequently used, these associations are indicated using a variety of expressions, showing a lack of consensus by specialists in the field. The main idea of this work is to analyze the variety of microbial associations referred to as "microbial consortia" (MC) in the context of pollutants biodegradation and bioremediation. To do that, we summarize the origin of the term pointing out the features that an MC is expected to meet, according to the opinion of several authors. An analysis of related bibliography was done seeking criteria to rationalize and classify MC in the context of bioremediation. We identify that the microbe's origin and the level of human intervention are usually considered as a category to classify them as natural microbial consortia (NMC), artificial microbial consortia (AMC), and synthetic microbial consortia (SMC). In this sense, NMC are those associations composed by microorganisms obtained from a single source while AMC members come from different sources. SMC are a class of AMC in which microbial composition is defined to accomplish a certain specific task. We propose that the effective or potential existence of the interaction among MC members in the source material should be considered as a category in the classification as well, in combination with the origin of the source and level of intervention. Cross-kingdom MC and new developments were also considered. Finally, the existence of grey zones in the limits between each proposed microbial consortia category is addressed. KEY POINTS: • Microbial consortia for bioremediation can be obtained through different methods. • The use of the term "microbial consortia" is unclear in the specialized literature. • We propose a simplified classification for microbial consortia for bioremediation.

Sex-specific association of high maternal psychological stress during pregnancy on newborn birthweight.

Birthweight is an important predictor of newborn health and has been linked to maternal psychological stress during pregnancy. However, it is unclear whether prenatal stress affects birthweight similarly for both male and female infants. We used a well-established pregnancy cohort to investigate the impact of high maternal psychological stress during pregnancy on birthweight as a function of infant sex. Overall, 5702 mother-newborn pairs were analysed. Of these, 198 mothers reported high levels of stress using the Psychological Stress Measure (nine-items version; PSM-9). Maternal psychological stress was assessed between the 24th and 28th week of gestation and analyses were performed jointly and independently as a function of neonatal sex (separate analyses for male and female infants). Newborns exposed to high maternal psychological stress during pregnancy (a score above 26 measured using the PSM-9 questionnaire, corresponding to >97.5th percentile) were compared to newborns of mothers who reported lower stress. ANCOVAs revealed that high levels of maternal stress during pregnancy were linked to infant birthweight as a function of infant sex. Male infants of mothers who reported high levels of stress had a greater birthweight whereas female infants had a lower birthweight under the same conditions, in comparison to mothers who did not report greater levels of stress. Although the effect size is small, these results underline the possibility that male and female fetuses may use different strategies when adapting to maternal adversity and highlight the need to consider infant sex as a moderator of the association between maternal psychological stress during pregnancy and infant birthweight.

Remote transmission monitoring for postoperative perineural analgesia after major orthopedic surgery: A multicenter, randomized, parallel-group, controlled trial.

STUDY OBJECTIVE: After surgery, patients reported the delay in receiving help as the primary factor for poorly controlled pain. This study aimed to compare the effectiveness of patient management through two communication modalities: remote transmission (RT) versus bedside control (BC). We hypothesized that using remote technology for pump programming may provide the best postoperative infusion regimen for the patient's self-assessment of pain and adverse events. DESIGN: A multicenter, randomized, parallel-group, controlled trial. SETTING: Anesthesiology department and orthopedic surgery ward at three university hospitals. PATIENTS: Eighty patients undergoing orthopedic surgery with postoperative perineural patient-controlled analgesia were included. INTERVENTIONS: Two groups (n = 40 for each group) were formed by randomization. In the postoperative period, perineural analgesia was followed up via an RT system or BC for 72 h. MEASUREMENTS: A nurse assessed daily pain, sensory and motor blocks and adverse events. Patients completed a questionnaire three times a day and alerted for any problem according to the group (RT system or nurses' follow-up). On the third postoperative day, the nurse removed the catheter, completed the final assessment, and collected the historical data from the pump. A physician's shorter response time to change the patient control analgesia (PCA) program was the primary endpoint. RESULTS: Of the 80 patients, 71 were analyzed (34 were randomized to the RT group and 37 to the BC group). Fifty-eight pump setting changes were noted. Analysis of repeated evaluations shows that mean time (SD) to change the PCA pump settings was significantly lower in the RT group (20 min (22.3 min)) than in the BC group (55.9 min (71.1 min)); mean difference [95% CI], -35.9 min [-74.3 to 2.4]); ß estimation [95% CI], -34 [-63 to -6], p = 0.011). Pain relief, sensory and motor blocks did not differ between the groups: ß estimation [95% CI], 0.1 [-0.4 to 0.6], p = 0.753; 0.5 [-0.4 to 1.4], p = 0.255; 0.9 [-0.04 to 1.8], p = 0.687, respectively. ß = -34 [-63 to -6], p = 0.011). The consumption of ropivacaine, nurse workload and the cost of the analgesia regimen decreased in the RT group. No differences were noted in satisfaction scores or complication rates. CONCLUSIONS: The response time for the physician to change the PCA program when necessary was shorter for patients using RT and alerts to the physician were more frequent compared with spot checks by nurses. RT helps to decrease nurses' workload, ropivacaine consumption, and costs but did not affect postoperative pain relief, complication rate, or patient-reported satisfaction score. IRB CONTACT INFORMATION: Comité de Protection des Personnes, Sud Méditerranée III, Montpellier-Nîmes, France, registration number EudraCT A01698-35. CLINICAL TRIAL NUMBER: ClinicalTrials.gov ID:NCT02018068 PROTOCOL: The full trial protocol can be accessed at Department of Anesthesiology and Critical Care Medicine, Medical Research and Statistics Unit, Lapeyronie University Hospital, Avenue Doten G Giraud, Montpellier, France. s-bringuierbranchereau@chu-montpellier.fr.

Impact of multiple nerves blocks anaesthesia on intraoperative hypotension and mortality in hip fracture surgery intermediate-risk elderly patients: A propensity score-matched comparison with spinal and general anaesthesia.

BACKGROUND: A Hip fracture in the intermediate-risk elderly patient is common and associated with a high rate of postoperative morbidity and mortality. There is a lack of consensus on the optimal anaesthetic technique but there is a clear association between intraoperative hypotension and postoperative morbidity and mortality. We aimed to compare the haemodynamic stability of three anaesthesia techniques: general anaesthesia (GA), continuous spinal anaesthesia (CSA), and multiple nerve blocks (MNB). METHODS: The primary outcome was the occurrence of intraoperative hypotension defined by a 30% decrease in mean arterial pressure (MAP) from baseline. Secondary outcomes included incidence of hypotension under 50 mmHg of MAP, time spent below MAP 50 mmHg, use of vasopressors, in-hospital and 30-day mortality. A propensity score-matched analysis was performed. RESULTS: After screening and application of the exclusion criteria, 593 patients undergoing hip fracture surgery between the 1st of January 2015 and the 31st of December 2016 were included. The propensity score match analysis selected 43 patients in each group. The incidence of hypotension was significantly higher in the GA group than in the MNB and CSA groups: 39 (90%), 22 (51%), and 23 (53.5%), respectively; p < 0.0001. The incidence of MAP < 50 mmHg (59.5%, 23.3%, and 16.3%; p < 0.0001) and the use of vasopressors (93%, 39.5%, and 25.6%; p < 0.0001) were increased significantly in the GA group. With the GA group as a reference, odds ratios were reported in the MNB group at 0.08 [0.022-0.30] (p = 0.0002) for hypotension episodes; 0.17 [0.04-0.66] (p = 0.01) for hypotension < 50 mmHg for more than 3 min and 0.049 [0.013-0.018] (p < 0.0001) for use of vasopressors. The duration of hospital stay, postoperative complications, in-hospital and 30-day mortality rates did not differ significantly between the groups. CONCLUSION: CSA and MNB provide better haemodynamic stability than GA. However, whatever the anaesthesia technique used, the mortality rates do not change even if MNB leads to less hypotension. IRB contact information: CERAR IRB 00010254-2016-118. Clinical Trial Number: ClinicalTrials.gov. ID: NCT03356704.

An uncommon cause of nerve stimulator's malfunction during a dual guidance lumbar plexus block: A technical brief report and an algorithm for prevention of complications.

Posterior Lumbar plexus block (PLPB) combined with an ipsilateral sacral plexus block is a valuable anaesthetic technique in patients undergoing hip fracture surgery. PLPB is performed through the acoustic window of the lumbar ultrasound trident and the position of the needle tip, before injection of LA, was confirmed by observing quadriceps femoris muscle contraction to peripheral nerve stimulation (i.e., dual guidance). We report an uncommon cause of nerve stimulator malfunction that might impair block performance and promote complications. We add an algorithm to limit the risk of complications.

Impact of maternal prenatal psychological stress on birth weight.

OBJECTIVE: The study aimed to evaluate the impact of prenatal maternal stress on birth weight using a large cohort of predominantly White women living in an urban area. METHOD: Women were recruited between 2005 and 2010. Data collection took place between the 24th and the 28th week of gestation. The Measure of Psychological Stress (MSP-9), a validated tool to assess stress symptoms, was used to collect data on prenatal maternal stress (independent variable). Birth weight (dependent variable) was classified as low birth weight (<2,500 g), normal birth weight (2,500-4,000 g), and macrosomia (>4,000 g). Adjusted odds ratios (aOR) were obtained after performing multivariate logistic regressions adjusted for potential cofounders. At the final stage, 5,721 women were included in analysis. RESULTS: When compared with women experiencing low stress, participants with high stress scores were at increased risk of delivering a newborn with low birth weight before adjustment (OR = 2.06, 95% CI [1.04, 4.09]), but after adjustment, only a nonsignificant trend remained. However, women experiencing intermediate and high levels of stress were at increased risk of delivering a newborn with macrosomia, even after adjustment (aOR = 1.23, [1.02, 1.49]) and (aOR = 1.76, [1.11, 2.77]) compared to those who scored low on the psychological stress scale. CONCLUSION: Women exposed to high psychological stress during the second trimester (24th to 28th weeks) of pregnancy have a 1.8-fold increased risk for delivering a newborn with macrosomia when compared to women exposed to low psychological stress. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Specific inflammatory profile in each pregnancy complication: A comparative study.

PROBLEM: Pre-eclampsia (PE), preterm birth (PTB) and intra-uterine growth restriction (IUGR) affect 5%-12% of pregnancies. They have been associated with placental inflammation, although the detection of inflammatory mediators in the maternal circulation is still controversial. Our goal was to determine the inflammatory changes occurring in the second part of pregnancy to identify profiles distinguishing pathological pregnancies from each other. METHOD OF STUDY: We performed a nested case-control study of 200 women randomly selected from a cohort recruited at the CHU de Quebec-Universite Laval, Quebec, Canada. Women with uncomplicated term pregnancy (CTRL); PE (severe or not); PTB or IUGR (N = 50/each) were included. Plasma samples, obtained from the late second trimester and at delivery, were analysed for over 30 selected mediators (including cytokines/alarmins), by multiplex, ELISA or specific assays. Demographic and obstetrical information were obtained for classification. RESULTS: In CTRL, we observed significant differences between 2nd trimester and delivery, with increased levels of inflammatory mediators (ex. MCP-1, IL-6), supporting an inflammatory profile towards term. Increased levels of IL-6, CXCL10 and CRP were observed in PE as compared to CTRL. In PTB, we observed increased CXCL9 in 2nd trimester and decreased progesterone at delivery. In IUGR, increased HMGB1 and IL-1α were observed only in the 2nd trimester. CONCLUSIONS: Our work showed significant inflammatory changes in uncomplicated pregnancies towards delivery, supporting that normal delivery is pro-inflammatory, although not to the same extent as in pathological pregnancies. Inflammatory profiles are specific to each pregnancy complication which may help to understand the contribution of inflammation to the clinical presentation of these conditions.

Study of sRAGE, HMGB1, AGE, and S100A8/A9 Concentrations in Plasma and in Serum-Extracted Extracellular Vesicles of Pregnant Women With Preterm Premature Rupture of Membranes.

Preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 37 weeks of gestation, complicates approximately 2-4% of pregnancies and is responsible for 40% of all spontaneous preterm births. PPROM arises from complex pathophysiological pathways with a key actor: inflammation. Sterile inflammation is a feature of senescence-associated fetal membrane maturity. During specific steps of sterile inflammation, cells also release highly inflammatory damage-associated molecular pattern markers (DAMPs), such as high-mobility group box 1 (HMGB1) or S100A8/A9, known to link and activate the receptor for advanced glycation end products (RAGE). The objective of this study was to measure longitudinally during pregnancy concentrations of the soluble form of RAGE (sRAGE) and its main ligands (AGE, HMGB1, S100A8/A9) in blood specimens. We studied 246 pregnant women (82 with PPROM and 164 matched control pregnant women without complications) from a cohort of 7,866 pregnant women recruited in the first trimester and followed during pregnancy until delivery. sRAGE, AGE, HMGB1, and S100A8/A9 concentrations were measured in plasma and in serum-extracted extracellular vesicles from first trimester (T1), second trimester (T2), and delivery (D). In plasma, we observed, in both PPROM and control groups, (i) a significant increase of HMGB1 concentrations between T1 vs. T2, T1 vs. D, but not between T2 vs. D; (ii) a significant decrease of sRAGE concentrations between T1 and T2 and a significant increase between T2 and D; (iii) a significant decrease of AGE from T1 to D; (iv) no significant variation of S100A8/A9 between trimesters. In intergroup comparisons (PPROM vs. control group), there were no significant differences in time variation taking into account the matching effects. There was a correlation between plasma and serum-extracted extracellular vesicle concentrations of sRAGE, AGE, HMGB1, and S100A8/A9. Our results suggest that the rupture of fetal membranes (physiological or premature) is accompanied by a variation in plasma concentrations of sRAGE, HMGB1, and AGE. The study of RAGE and its main ligands in extracellular vesicles did not give additional insight into the pathophysiological process conducting to PPROM.

Cord blood S100B: reference ranges and interest for early identification of newborns with brain injury.

Background Neurological complications are common in the premature and full-term neonates admitted to the intensive care unit, but the diagnosis of these complications is often difficult to make. S100B protein, measured in cord blood, may represent a valuable tool to better identify patients at risk of brain injury. Methods As a first step, we established S100B cord blood serum reference intervals from 183 preterm and 200 full-term neonates. We then measured cord blood serum S100B to identify neurological complications in 272 neonates hospitalized at the neonatal intensive care unit (NICU). Diagnosis of brain injury relied on imaging examination. Results The 95th percentiles of S100B concentration in cord blood were established as 1.21 µg/L for the 383 neonates, 0.96 µg/L for full-term neonates and 1.36 µg/L for premature neonates. Among the 272 neonates hospitalized at the NICU, 11 presented neurological complications. Using 1.27 µg/L as the optimal sensitivity/specificity threshold, S100B differentiate neonates with and without neurological complications with a sensitivity of 45.5% (95% confidence intervals [CI]: 16.7-76.6) and a specificity of 88.9% (95% CI: 84.4-92.4) (p = 0.006). In combination with arterial pH (<7.25), sensitivity increased to 90.9% (95% CI: 58.7-99.8), while specificity was 51.2% (95% CI: 44.8-57.7). The sensitivity is significantly (p = 0.03) increased in comparison to S100B alone. The specificity is significantly higher with S100B only than with pH + S100B (p < 0.001). Conclusions Cord blood S100B protein, in combination with arterial cord blood pH, has the potential to help clinicians to detect at birth neurological complications in neonates hospitalized in an NCIU.

Association of Maternal Weight and Gestational Weight Gain with Maternal and Neonate Outcomes: A Prospective Cohort Study.

We investigated the association of outcomes with pre-pregnancy body mass index (ppBMI), Institute of Medicine (IOM) recommendations about gestational weight gain, and weight gain trajectories during pregnancy. A prospective cohort of 7866 pregnant women was recruited. ppBMI and weight gain at each follow up visit were collected. The outcomes were gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), caesarean delivery, macrosomia, small (SGA) and large (LGA) for gestational age, neonatal hypoglycemia. Group-based multi-trajectory modelling was used for weight kinetics during pregnancy. In the third trimester, 53.8% of women were above IOM recommendations, with an increased relative risk (RR) of HDP (1.91 (1.40-2.61)), caesarean (1.34 (1.15-1.56)), macrosomia (2.17 (1.77-2.67)), LGA (2.26 (1.83-2.80)), and hypoglycemia (1.89 (1.12-3.18)). Women with a weight gain above IOM recommendations in the second trimester who normalized their weight gain in third trimester had, compared to those who remained above IOM recommendations, fewer events of HDP (2.8% versus 5.3%, p = 0.008), caesarean delivery (16.9% versus 22%, p = 0.006), macrosomia (8.3% versus 14.2%, p < 0.001), and LGA (7% versus 13.2%, p < 0.001). Multi-trajectory modelling identified three profiles with continued variation in RR of complications, including GDM. Weight gain above IOM recommendations increased the risk of perinatal complications. A correction of excessive weight gain in the second trimester reduces these risks.

Risk Factors and Outcomes of Preterm Premature Rupture of Membranes in a Cohort of 6968 Pregnant Women Prospectively Recruited.

We revisited risk factors and outcomes related to the preterm premature rupture of membranes (PPROM). A total of 7866 pregnant women were recruited during 5 years at their first prenatal visit to the perinatal clinic of the institution. We compared three groups (women without prematurity, women with spontaneous preterm labor with intact membranes (sPL with IM), women with PPROM) regarding 60 criteria about characteristics, lifestyle, medical, gynecological, obstetrical history of mothers, medication during pregnancy, events at delivery, and complications in neonates. Logistic regression analyses adjusting for potential confounding factors were used. Of the 6968 women selected, 189 (2.8%) presented a PPROM, and 225 (3.2%) an sPL with IM. The specific risk factors for PPROM were body mass index (BMI) <18.5 kg/m2 (adjusted odds ratio, aOR: 2.00 (1.09-3.67)), history of PPROM (aOR: 2.75 (1.19-6.36)), nulliparity (aOR: 2.52 (1.77-3.60)), gestational diabetes (aOR: 1.87 (1.16-2.99)), and low level of education (aOR: 2.39 (1.20-4.78)). The complications associated with PPROM were abruption placentae, cesarean, APGAR 5' <4, birth weight <2500 g, stillbirth, neonatal jaundice, and hospitalization of mother and neonates. All these complications were also associated with sPL with IM. Our study confirms some of the risk factors of PPROM and highlights a new one: gestational diabetes. Outcomes of PPROM are related to prematurity.

Use of antidepressants and anxiolytics in early pregnancy and the risk of preeclampsia and gestational hypertension: a prospective study.

BACKGROUND: We investigated the association between antidepressant and anxiolytic exposure during the first and early second trimester of pregnancy (< 16 weeks), and hypertensive disorders of pregnancy (including preeclampsia and gestational hypertension) in women with singleton pregnancy. METHODS: This study is based on a large prospective cohort of 7866 pregnant women. We included pregnant women aged 18 years or older without chronic hepatic or renal disease at the time of recruitment. Participants lost to the follow-up, with multiple pregnancies and pregnancy terminations, miscarriages or fetal deaths before 20 weeks of gestation were excluded from the study, as well as women with no data on the antidepressant/anxiolytic medication use during pregnancy. Information concerning antidepressant or anxiolytic medication use was extracted from hospital records after delivery. The associations between their use and the risk of gestational hypertension or preeclampsia were calculated. RESULTS: The final sample for analysis included 6761 participants including 218 (3.2%) women who were exposed to antidepressant and/or anxiolytic medication before the 16th week of gestation. Forty-one women had a non-medicated depression or anxiety during the pregnancy. Moreover, 195 (2.9%) and 122 (1.8%) women developed gestational hypertension and preeclampsia respectively. When compared to women unexposed to antidepressant/anxiolytic medication, depression and anxiety, those using antidepressant and/or anxiolytic drugs before the 16th week of gestation were at increased risk of preeclampsia (adjusted odd ratio (aOR) 3.09 [CI95% 1.56-6.12]), especially if they continued their medication after the 16th week (aOR 3.41 [CI95% 1.66-7.02]) compared to those who did not (1.60 [CI95% 0.21-12.34]). CONCLUSIONS: Women exposed to antidepressant and/or anxiolytic medication before the 16th week of pregnancy have a 3-fold increased risk for preeclampsia when compared to women unexposed to antidepressant/anxiolytic medication, depression and anxiety. Also, our results suggested that women who stopped their medication before the 16th week of pregnancy could be benefit from reduced preeclampsia risk.

Comparison of axillary nerve block duration using mepivacaine in non-insulin diabetic or renal insufficiency patients: a controlled observational matched multicenter trial.

BACKGROUND: Although studies in diabetic patients demonstrated delayed recovery after long-acting local anesthetic, its effects with short-acting LA remains to be determined. Using mepivacaine, the authors evaluated the duration of axillary nerve blocks in diabetic (DP), renal failure (creatinine clearance <30 mL.min-1) (RP) and healthy patients (HP). METHODS: We prospectively included consecutive patients aged 18-80 years, with DP (N.=37), RP (N.=32) and HP (N.=48) scheduled for distal upper limb surgery. Before surgery, an axillary nerve block (20 mL mepivacaine 15 mg.mL-1) was performed with an ultrasound approach combined with nerve stimulation. Five mL was injected for each nerve: median, ulnar, radial, musculocutaneous nerves. The primary endpoint measured was the duration of sensory block. For statistical analysis, each HP patient was matched with RP and DP patient (1:1), with regards to age (range±5 years) and sex. RESULTS: Patient characteristics were similar between groups. Creatinine clearance was 14±8 mL.min-1 in RP group and HbA1c (%) was 7.5±1.5 in DP group. Mean duration of diabetic or renal insufficiency illness were respectively eight and 12 years. Onset time for sensory and motor blocks were similar between groups. Average time for sensory block duration was similar between DP vs. HP (235±52 vs. 230±54 min, P=0.71); and between RP vs. HP (234±51 vs. 229±57 min, P=0.65). CONCLUSIONS: The short-acting LA (mepivacaine) are associated with similar pharmacodynamic effects in diabetic and renal failure patients as compared with healthy patients.

Pregnancy outcomes in women on metformin for diabetes or other indications among those seeking teratology information services.

AIMS: Metformin is used to treat type 2 diabetes, polycystic ovary syndrome associated infertility, and gestational diabetes. This study aims to evaluate the safety of metformin in early pregnancy. METHOD: We evaluated the risk of major birth defects and pregnancy losses in a cohort of pregnant women exposed to metformin during the first trimester for different indications relative to a matched unexposed reference group. RESULTS: The risk of major birth defects was 5.1% (20/392) in pregnancies exposed to metformin during the first trimester and 2.1% (9/431) in the reference group [adjusted odds ratio (OR) 1.70; 95% CI 0.70-4.38]. Among metformin users, this risk was 7.8% (17/219) in patients with pre-gestational diabetes and 1.7% (3/173) in those without this diagnosis. Compared to the unexposed reference, the OR for metformin user with diabetes was 3.95 (95% CI 1.77-9.41) and for metformin with other indications it was 0.83 (95% CI 0.18-2.81). The risk of pregnancy losses (spontaneous abortions and stillbirths) was 20.8% in women on metformin during the first trimester and 10.8% in the reference group [adjusted hazard ratio (HR) 1.57; 95% CI 0.90-2.74]. The risks for women on metformin with and without pre-gestational diabetes were 24.0% and 16.8% respectively, with adjusted HR of 2.51 (95% CI 1.44-4.36) and 1.38 (95% CI 0.74-2.59) when compared to the reference. CONCLUSION: Pregnant women with pre-gestational diabetes on metformin are at a higher risk for adverse pregnancy outcomes than the general population. This appears to be due to the underlying diabetes since women on metformin for other indications do not present meaningfully increased risks.

Pregnancy outcome following maternal exposure to pregabalin may call for concern.

OBJECTIVE: To investigate pregnancy outcomes following maternal use of pregabalin. METHODS: This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to pregabalin with those of matched controls (not exposed to any medications known to be teratogenic or to any antiepileptic drugs). Teratology Information Services systematically collected data between 2004 and 2013. RESULTS: Data were collected from 164 exposed pregnancies and 656 controls. A significantly higher major birth defect rate in the pregabalin group was observed after exclusion of chromosomal aberration syndromes, and when cases with exposure during first trimester of pregnancy were analyzed separately (7/116 [6.0%] vs 12/580 [2.1%]; odds ratio 3.0, 95% confidence interval 1.2-7.9, p = 0.03). The rate of live births was lower in the pregabalin group (71.9% vs 85.2%, p < 0.001), primarily due to a higher rate of both elective (9.8% vs 5.0%, p = 0.02) and medically indicated (5.5% vs 1.8%, p = 0.008) pregnancy terminations. In the Cox proportional cause specific hazards model, pregabalin exposure was not associated with a significantly higher risk of spontaneous abortion. CONCLUSIONS: This study demonstrated a signal for increased risk of major birth defects after first trimester exposure to pregabalin. However, several limitations such as the small sample size, differences across groups in maternal conditions, and concomitant medication exposure exclude definitive conclusions, so these results call for confirmation through independent studies.

[Pregnancy outcome after preconceptional exposure to methotrexate for ectopic pregnancy]. / Méthotrexate pour grossesse extra-utérine : quels risques en cas de nouvelle grossesse ?

INTRODUCTION: Methotrexate (MTX) is a known teratogenic drug used off-label in the treatment of ectopic pregnancies (EP). As MTX polyglutamated derivatives remains into the cells during several weeks, it is recommended to avoid conception during 3 to 6 months following MTX therapy. We report the follow-up of pregnancies after preconceptional exposure to MTX for EP. MATERIAL/METHODS: Prospective cases of pregnancy occurring within 3 months after MTX injection for an EP recorded in the Terappel database were analyzed. RESULTS: Data were obtained on 52 pregnant women. The median age of patients was 28 (18-38), and the median gestational age at inclusion was 7 weeks after last menstrual period (3-22). The time between the last MTX injection and conception ranged from 12 days to 13 weeks and the total MTX dose was between 40 to 210mg. Out of 45 pregnancies with known outcome, there were 39 live births (87%), 3 spontaneous abortions (6.7%) occurring 63 to 94 days after MTX administration, 2 elective terminations, and 1 medical termination after premature rupture of membranes, oligohydramnios and arthrogryposis (48mg of MTX 9 and 8 weeks before conception). Two additional cases of major malformations were observed among 40 examinable babies or fetuses: tetralogy of Fallot (MTX 6 weeks before conception), and cerebral ventriculomegaly with normal karyotype (50mg of MTX 9 to 13 weeks before conception). The resulting rate of major malformations was 7.5% (95% CI: 1.6-20.4). DISCUSSION/CONCLUSION: Although this prospective study shows a major malformation rate higher than expected in the general population, the observed malformations are not consistent with the typical pattern of methotrexate embryopathy. However, the case of tetralogy of Fallot is reminiscent of previously published cases with MTX exposure during early pregnancy. Owing to the small sample size, more powerful studies are needed to confirm or refute these findings.