Epidemiology of gout and hyperuricemia in New Caledonia

ObjectivesNew Caledonia is a Pacific island of 270,000 inhabitants with mixed ethnicities, including Polynesians (10.2%), people from European ancestry (27.2%), and Melanesians (39.1%),. This study aimed at determining the prevalence of gout and hyperuricemia in the general population and the various ethnicities of New Caledonia.MethodsA 3-degree random sample of the population aged 18 to 60 years was adjusted according to the 2014 New Caledonia census. Face-to-face planned interviews and physical measurements were performed by trained nurses. All consenting participants underwent capillary measurement of creatinine; all consenting men and only women older than 40 years underwent point-of-care uricemia testing. Gout was defined by a validated algorithm. Two definitions of hyperuricemia were used: capillary level equivalent to plasma uric acid level > 360 μmol/l (6 mg/dl) and > 420 μmol/l (7 mg/dl) and/or urate-lowering drug treatment for both thresholds.ResultsWe included 1144 participants (adjusted mean age 37.7 ± 12.0 years; adjusted sex ratio 50.4% men). The adjusted prevalence of gout was 3.3% (95% confidence interval 2.2–4.9). Prevalence was 6.7% (2.5–16.8), 4.1% (1.8–8.9), and 2.6% (1.4–4.7) for Polynesians, Europeans and Melanesians, respectively, and 1.9% (0.5–6.6) for other ethnicities. Prevalence of hyperuricemia, determined in 658 participants, was 67.0% (61.9–71.6) and 37.0% (32.3–42.0) for the 360- and 420-μmol/l thresholds, respectively, and was significantly greater for Polynesians and Melanesians than Europeans for both thresholds.ConclusionsThe prevalence of gout and hyperuricemia in New Caledonia was high, including in patients of European descent.     

HLA association with the susceptibility to anti-synthetase syndrome

ObjectiveTo investigate the human leukocyte antigen (HLA) association with anti-synthetase syndrome (ASSD).MethodsWe conducted the largest immunogenetic HLA-DRB1 and HLA-B study to date in a homogeneous cohort of 168 Caucasian patients with ASSD and 486 ethnically matched healthy controls by sequencing-based-typing.ResultsA statistically significant increase of HLA-DRB1*03:01 and HLA-B*08:01 alleles in patients with ASSD compared to healthy controls was disclosed (26.2% versus 12.2%, P = 1.56E–09, odds ratio–OR [95% confidence interval–CI] = 2.54 [1.84–3.50] and 21.4% versus 5.5%, P = 18.95E–18, OR [95% CI] = 4.73 [3.18–7.05]; respectively). Additionally, HLA-DRB1*07:01 allele was significantly decreased in patients with ASSD compared to controls (9.2% versus 17.5%, P = 0.0003, OR [95% CI] = 0.48 [0.31–0.72]). Moreover, a statistically significant increase of HLA-DRB1*03:01 allele in anti-Jo-1 positive compared to anti-Jo-1 negative patients with ASSD was observed (31.8% versus 15.5%, P = 0.001, OR [95% CI] = 2.54 [1.39–4.81]). Similar findings were observed when HLA carrier frequencies were assessed. The HLA-DRB1*03:01 association with anti-Jo-1 was unrelated to smoking history. No HLA differences in patients with ASSD stratified according to the presence/absence of the most representative non-anti-Jo-1 anti-synthetase autoantibodies (anti-PL-12 and anti-PL-7), arthritis, myositis or interstitial lung disease were observed.ConclusionsOur results support the association of the HLA complex with the susceptibility to ASSD.     

Comprehensive assessment of sensitizing events and anti-HLA antibody development in women awaiting kidney transplantation

BackgroundAlloimmunization remains a critical factor which affects the success of kidney transplantation. Patients awaiting solid organ transplantation may develop anti-HLA antibodies after pregnancies, transfusions and previous events of transplantations.AimWe evaluated the effects of different sensitizing events on the anti-HLA antibody production and the potential role of patient HLA alleles in the context of antibody development in both the overall and pregnancy sensitized groups.Material and methodsWe retrospectively stratified 411 women on waiting list for kidney transplantation by route of sensitization. The presence of anti-HLA antibodies was evaluated by Solid Phase Assay and HLA typing was performed by serological and molecular methods.ResultsIn our study population, 54% of women had anti-HLA antibodies. We found that the 51.6% of women with pregnancy only, 44% of women with transfusion only and 100% of women with a history of transplantation only developed anti-HLA antibodies. Pregnancy only resulted significantly associated with all anti-HLA antibody development such as anti-A, -B, -C, -DR, -DP as well as anti-DQB and -DQA antibodies. We investigated the influence of patient HLA alleles on the antibody development in the overall study population. Patients expressing HLA A*32 (p = 0.024, OR = 0.42), B*14 (p = 0.035, OR = 0.44), HLA-B*44 (p = 0.026, OR = 0.51) and DRB1*01 (p = 0.029, OR = 0.55) alleles produced anti-HLA antibodies less frequently compared to subjects with other alleles. In the pregnancy only group, B*14 (p = 0.010, OR = 0.12) and B*51 (p = 0.005, OR = 0.24) alleles were associated with a low risk of anti-HLA antibody development, while A*11 (p = 0.033, OR = 3.56) and DRB1*04 (p = 0.022, OR = 3.03) alleles seem to represent a higher risk.ConclusionsPregnancy still remains a strong sensitizing event in women awaiting kidney transplantation. The anti-HLA antibody development in pregnancy appears to be associated with the expression of particular HLA alleles.     

HLA-DRB1 Alleles are Associated With COPD in a Latin American Admixed Population

IntroductionWhile the molecular mechanisms of COPD pathogenesis remain obscure, there is mounting evidence supporting a key role for autoimmunity. Although human leukocyte antigens (HLA) alleles have been repeatedly associated with autoimmune processes, the relation between HLA and COPD remains largely unexplored, especially in Latin American (LA) populations. Consequently, this study aimed to investigate the presence of HLA class I and II alleles in COPD patients and healthy controls in a LA population with admixed ancestry.MethodsCOPD patients (n = 214) and age-matched controls (n = 193) were genotyped using the Illumina Infinium Global Screening Array. The classic HLA alleles were imputed using HLA Genotype Imputation with Attribute Bagging (HIBAG) and the Hispanic reference panel. Finally, the distribution of HLA-DRB1 alleles was reexamined in 510 randomly recruited unrelated volunteers.ResultsCODP patients showed a higher HLA-DRB1*01:02 allele frequency (6.54%) than healthy controls (3.27%, p = 0.04, OR = 2.07). HLA-DRB1*01:02 was also significantly associated with FEV₁ (p = 0.04) and oxygen saturation (p = 0.02), and the FEV₁/FVC ratio was higher in HLA-DRB1*15:01-positive patients (p = 9 × 10^?3).ConclusionWe report an association among HLA-DRB1 alleles, COPD risk and pulmonary function parameters for the first time in Latin Americans. Since HLA-DRB1 genetic variability relates to the individual autoimmune response, these results support a role of autoimmunity in the pathogenesis of COPD.     

Palpable tophi and more comorbidities associated with adherence to urate-lowering medical therapy in a Chinese gout cohort

ObjectiveUrate-lowering therapy (ULT) nonadherence is common and problematic in gout. Since, sociocultural factors affect adherence, we analyzed a Chinese cohort.MethodsWe studied 903 Chinese gout patients aged 46.4 ± 14.7 years (mean ± SD), uniquely extending to assay of 2-year medication possession ratio (MPR) ≥80% defined as high adherence. Multivariable logistic regression analyses evaluated factors linked with adherence and ULT target attainment.ResultsCharacterization of ULT outcomes in this cohort revealed that after 2 years ULT, MPR ≥80% patients had better target serum urate (SU) achievement (from 23.3% to 71.0%, P < 0.001), lower flare frequency and palpable tophi compared to MPR < 80%. However, only 44.7% of cohort subjects had MPR ≥80%. Male sex (OR 3.68), gout onset age >60 years (OR 3.51), disease duration >5 years (OR 1.70), more comorbidities (OR 1.74), baseline palpable tophi (OR 1.53), SU < 6 mg/dL (360 μmol/L) (OR 1.92) and more frequent follow-up visits (OR 1.98) were significantly associated with high adherence. Nevertheless, significant independent risk factors for failed SU target achievement included male sex (OR 0.36) and more comorbidities (OR 0.85).ConclusionDespite adherence to ULT linked to better outcomes for flares and tophi, the more adherent Chinese male patients and those with more comorbidities had decreased target SU attainment. Differences in adherence of Chinese gout patients compared to several primarily Western studies emphasize the importance of not stereotyping gout patients for projected nonadherence. Results underline the dual importance of identifying gout patients more likely to be ULT-adherent and leveraging adherence to drive treatment to SU target.     

UltraSound evaluation in follow-up of urate-lowering therapy in gout phase 2 (USEFUL-2): Duration of flare prophylaxis

ObjectivesTo determine whether changes in ultrasonography (US) features of monosodium urate crystal deposition is associated with the number of gouty flares after stopping gout flare prophylaxis.MethodsWe performed a 1-year multicentre prospective study including patients with proven gout and US features of gout. The first phase of the study was a 6-month US follow-up after starting urate-lowering therapy (ULT) with gout flare prophylaxis. After 6 months of ULT, gout flare prophylaxis was stopped, followed by a clinical follow-up (M6 to 12) and ULT was maintained. Outcomes were the proportion of relapsing patients between M6 and M12 according to changes of US features of gout and determining a threshold decrease in tophus size according to the probability of relapse.ResultsWe included 79 gouty patients [mean (± SD) age 61.8 ± 14 years, 91% males, median disease duration 4 (IQR 1.5;10) years]. Among the 49 completers at M12, 23 (47%) experienced relapse. Decrease in tophus size ≥ 50% at M6 was more frequent without than with relapse (54% vs. 26%, P = 0.049). On ROC curve analysis, a threshold decrease of 50.8% in tophus size had the best sensitivity/specificity ratio to predict relapse [AUC 0.649 (95% confidence interval 0.488; 0.809)]. Probability of relapse was increased for patients with a decrease in tophus size < 50% between M0 and M6 [OR 3.35 (95% confidence interval 0.98; 11.44)].ConclusionA high reduction in US tophus size is associated with lower probability of relapse after stopping gout prophylaxis. US follow-up may be useful for managing ULT and gout flare prophylaxis.     

Influence of the CYP2J2 Gene Polymorphisms on Chronic Obstructive Pulmonary Disease Risk in the Chinese Han Population

IntroductionCytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility.Material and methodsA case–control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk.ResultsWe observed rs11207535 (homozygote: OR = 0.08, 95%CI = 0.01–0.96, p = 0.047; recessive: OR = 0.08, 95%CI = 0.01–0.94, p = 0.044), rs10889159 (homozygote: OR = 0.08, 95%CI = 0.01–0.92, p = 0.043; recessive: OR = 0.08, 95%CI = 0.01–0.90, p = 0.040) and rs1155002 (heterozygote: OR = 1.63, 95%CI = 1.13–2.36, p = 0.009; dominant: OR = 1.64, 95%CI = 1.15–2.35, p = 0.006; additive: OR = 1.45, 95%CI = 1.09–1.92, p = 0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p < 0.05). Additionally, two haplotypes (A_rs11207535C_rs10889159T_rs1155002 and A_rs11207535C_rs10889159C_rs1155002) significantly decreased COPD risk.ConclusionIt suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population.     

Blunt splenic injury: Outcomes of proximal versus distal and combined splenic artery embolization

PurposeTo assess clinical outcomes of blunt splenic injuries (BSI) managed with proximal versus distal versus combined splenic artery embolization (SAE).Materials and methodsAll consecutive patients with BSI admitted to our trauma centre from 2005 to 2010 and managed with SAE were reviewed. Outcomes were compared between proximal (P), distal (D) or combined (C) embolization. We focused on embolization failure (splenectomy), every adverse events occurring during follow up and material used for embolization.ResultsFifty patients were reviewed (P n = 18, 36%; D n = 22, 44%; C n = 8, 16%). Mean injury severity score was 20. The technical success rate was 98%. Four patients required splenectomy (P n = 1, D n = 3, C n = 0). Clinical success rate for haemostasis was 92% (4 re-bleeds: P n = 2, D n = 2, C n = 0). Outcomes were not statistically different between the materials used. Adverse events occurred in 65% of the patients during follow up. Four percent of the patients developed major complications and 56% developed minor complications attributable to embolization. There was no significant difference between the 3 groups.ConclusionSAE had an excellent success rate with adverse events occurring in 65% of the patients and no significant differences found between the embolization techniques used. Proximal preventive embolization appears to protect in high-grade traumatic injuries.     

Evaluation of febuxostat initiation during an acute gout attack: A prospective,randomized clinical trial

ObjectiveUrate-lowering treatment (ULT) is recommended in gout management. However, initiation of ULT during an acute gout flare is still inconclusive. This study aimed to evaluate the efficacy and safety of the ULT febuxostat administered at initiation of an acute gout attack.MethodsA prospective randomized controlled clinical trial was conducted for 12 weeks in primary gout patients who were admitted with acute gout attacks. Subjects were randomly assigned to the febuxostat group in which febuxostat, 40 mg daily, was administered in the primary care setting for attacks, or to the control group in which febuxostat, 40 mg daily, was administered after the attacks. All patients received adequate anti-inflammatory and analgesic therapies. Serum urate (SU) levels were monitored throughout the study. Pain, measured using a visual analogue scale (VAS), and gout recurrence rate were used as primary outcomes. Flare-related inflammation biomarkers were selected as secondary outcomes.ResultsFifty-two patients completed the study (febuxostat group: n = 28; control group: n = 24). No significant differences were detected in VAS scores between the two groups over the first 14-day observation period (P > 0.05). Administration of febuxostat decreased SU levels significantly during the first 2-week period. However, the gout recurrent rate or gout flare-related inflammation indicators did not change in the febuxostat or control groups. Treatment-related adverse events were mild and similar between groups.ConclusionInitiation of the urate-lowering drug febuxostat during an acute gout attack caused no significant difference in daily pain, recurrent flares, or adverse effects. The treatment significantly decreased SU levels in the early stage and might have potential long-term benefits in these patients.     

Predictive factors of tumour necrosis inhibitor treatment persistence for rheumatoid arthritis: An observational study in 8052 patients

ObjectivesTo determine whether changes in ultrasonography (US) features of monosodium urate crystal deposition is associated with the number of gouty flares after stopping gout flare prophylaxis.MethodsWe performed a 1-year multicentre prospective study including patients with proven gout and US features of gout. The first phase of the study was a 6-month US follow-up after starting urate-lowering therapy (ULT) with gout flare prophylaxis. After 6 months of ULT, gout flare prophylaxis was stopped, followed by a clinical follow-up (M6 to 12) and ULT was maintained. Outcomes were the proportion of relapsing patients between M6 and M12 according to changes of US features of gout and determining a threshold decrease in tophus size according to the probability of relapse.ResultsWe included 79 gouty patients (mean [± SD] age 61.8 ± 14 years, 91% males, median disease duration 4 [IQR 1.5; 10] years). Among the 49 completers at M12, 23 (47%) experienced relapse. Decrease in tophus size ≥ 50% at M6 was more frequent without than with relapse (54% vs. 26%, P = 0.049). On ROC curve analysis, a threshold decrease of 50.8% in tophus size had the best sensitivity/specificity ratio to predict relapse. Probability of relapse was increased for patients with a decrease in tophus size <50% between M0 and M6 (OR 3.35 [95% confidence interval 0.98; 11.44]).ConclusionA high reduction in US tophus size is associated with low probability of relapse after stopping gout prophylaxis. US follow-up may be useful for managing ULT and gout flare prophylaxis.     

Bilateral sphenopalatine ganglion block as adjuvant to general anaesthesia during endoscopic trans-nasal resection of pituitary adenoma

BackgroundThis study was conducted to investigate the anaesthetic, vasodilator, and post-operative analgesic sparing effect of bilateral sphenopalatine ganglion block (SPGB) in patients undergoing endoscopic endo-nasal trans-sphenoidal surgery.MethodsThirty adult patients of ASA (I, II), aged 20–60 years, were randomly allocated to either the block group or the non-block group (n = 15, for each). After establishment of general anesthesia with sevoflurane and 100% oxygen, the patients received bilateral SPGB with 1.5 ml of either 0.5% bupivacaine (block group) or 0.9% NaCl (non-block group). Intra-operative mean arterial pressure (MAP) was maintained at 60–65 mmHg by using nitroglycerine. End-tidal sevoflurane concentration required to maintain bispectral index values (40–50) throughout the operation was recorded. Nitroglycerine and propranolol consumption, blood loss, recovery profile, perioperative catecholamines, post-operative pain and meperidine consumption were evaluated.ResultsBlock group showed significant decrease in sevoflurane and nitroglycerine consumption, blood loss, emergence time and time needed to achieve ?9 Aldrete score, P < 0.0001. All patients in non-blockade group (100%) were supplemented by nitroglycerine to achieve the target MAP versus 9 patients (60%) in the block group (P < 0.01). Propranolol administration was necessary in 9 patients (60%) in the non-block group versus 3 patients (20%) in the block group, P < 0.05. At PACU, visual analogue pain score and number of patients received meperidine analgesia were significantly less in the block group versus non-block group, P < 0.0001 and P < 0.001, respectively. Intra- and post-operative plasma epinephrine and nor-epinephrine levels were significantly higher in the non-block group than the block group, P < 0.05.ConclusionBilateral SPGB has anaesthetic, vasodilator and analgesic sparing effect when combined with general anaesthesia during endoscopic endo-nasal trans-sphenoidal resection of pituitary adenoma.     

GLPG2737 in lumacaftor/ivacaftor-treated CF subjects homozygous for the F508del mutation: A randomized phase 2A trial (PELICAN)

BackgroundTriple combinations of cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators demonstrate enhanced clinical efficacy in CF patients with F508del mutation, compared with modest effects of dual combinations. GLPG2737 was developed as a novel corrector for triple combination therapy.MethodsThis multicenter, randomized, double-blind, placebo-controlled, phase 2a study evaluated GLPG2737 in F508del homozygous subjects who had been receiving lumacaftor 400 mg/ivacaftor 250 mg for ≥12 weeks. The primary outcome was change from baseline in sweat chloride concentration. Other outcomes included assessment of pulmonary function, respiratory symptoms, safety, tolerability, and pharmacokinetics.ResultsBetween November 2017 and April 2018, 22 subjects were enrolled and randomized to oral GLPG2737 (75 mg; n = 14) or placebo (n = 8) capsules twice daily for 28 days. A significant decrease from baseline in mean sweat chloride concentration occurred at day 28 for GLPG2737 versus placebo (least-squares-mean difference − 19.6 mmol/L [95% confidence interval (CI) –36.0, −3.2], p = .0210). The absolute improvement, as assessed by least-squares-mean difference in change from baseline, in forced expiratory volume in 1 s (percent predicted) at day 28 for GLPG2737 versus placebo was 3.4% (95% CI –0.5, 7.3). Respiratory symptoms in both groups remained stable. Mild/moderate adverse events occurred in 10 (71.4%) and 8 (100%) subjects receiving GLPG2737 and placebo, respectively. Lower exposures of GLPG2737 (and active metabolite M4) were observed than would be expected if administered alone (as lumacaftor induces CYP3A4). Lumacaftor and ivacaftor exposures were as expected.ConclusionsGLPG2737 was well tolerated and yielded significant decreases in sweat chloride concentration versus placebo in subjects homozygous for F508del receiving lumacaftor/ivacaftor, demonstrating evidence of increased CFTR activity when added to a potentiator–corrector combination.FundingGalapagos NV.Clinical trial registration: ClinicalTrials.gov identifier, NCT03474042     

Detection of plasma cells,C4d deposits and donor-specific antibodies on sequential graft biopsies of renal transplant recipients with chronic dysfunction

BackgroundIn order to look for a relationship between humoral mechanisms of rejection and chronic allograft dysfunction, plasma cells, C4d deposits and donor-specific antibodies (DSA) were simultaneously sought on serial biopsies of kidney allograft recipients.Patients and methodsTen recipients with chronic dysfunction (G1) and 8 recipients with long-term normal graft function (G2) were included. Biopsies and serums were sampled at early graft dysfunction (T1), between 8 months and 2 years (T2) and after the third year following transplantation (T3).ResultsIn G1, plasma cells represented 12.3% (T1), 8.2% (T2) and 14.1% (T3) of mononuclear cells. The mean percentage of plasma cells was 11.6% in G1 versus 0.4% in G2 (p < 0.05). A progressive rise in C4d deposits was seen in G1, from 25% at T1 to 80% at T3. Donor-specific antibodies were identified in at least one serum sample of 60% of the patients in G1 and 12.5% of the patients in G2 (p = 0.012), whereas donor-specific antibodies were eluted from at least one biopsy of 50% of the patients in G1 and 12.5% of the patients in G2 (p = 0.03). In G1, C4d deposits were significantly associated with plasma cells (p = 0.0012) and anti-HLA Abs in serum samples and/or eluates (p = 0.026).ConclusionThis study shows that plasma cells, DSA and C4d are associated in renal transplants developing chronic rejection.     

Residual neuromuscular block as a risk factor for critical respiratory events in the post anesthesia care unit

ObjectiveResidual neuromuscular block is an important postoperative complication associated to the use of neuromuscular blocking drugs. The purpose of this study was to access the incidence of residual neuromuscular block in a post-anesthesia care unit and to evaluate its association with critical respiratory events.Material and methodsProspective cohort study was conducted in a Post Anesthetic Care Unit (PACU) for a period of 3 weeks. Two hundred two adult patients who submitted to scheduled non-cardiac and non-intracranial surgery were eligible to the study. The primary outcome variable was residual neuromuscular block after arrival to PACU that was defined as train-of-four ratio <0.9 and objectively quantified using acceleromyography. Demographic data, perioperative variables, lengths of hospital and recovery room stay and critical respiratory events were recorded. Inadequate emergence was classified in its different forms according to the Richmond agitation and sedation scale 10 min after admission to the recovery room.ResultsResidual neuromuscular block incidence in the post-anesthesia care unit was 29.7% (95% confidence interval: 23.4, 36.1). Patients with residual neuromuscular block had more frequently overall critical respiratory events (51% versus 16%, P < 0.001), airway obstruction (10% versus 2%, P = 0.029), mild-moderate hypoxemia (23% versus 4%, P < 0.001), severe hypoxemia (7% versus 1%, P = 0.033), respiratory failure (8% versus 1%, P = 0.031), inability to breathe deeply (38% versus 12%, P < 0.001) and muscular weakness (16% versus 1%, P < 0.001). Residual neuromuscular block was more common after high-risk surgery (53% versus 33%, P = 0.011) and was more often associated with post-operative hypoactive emergence as defined by the Richmond Agitation and Sedation Scale (21% versus 6%, P = 0.001).ConclusionsThis study suggests that residual neuromuscular block is common in the PACU and is associated with more frequent critical respiratory events.     

The effect of bupivacaine with fentanyl temperature on initiation and maintenance of labor epidural analgesia: a randomized controlled study

BackgroundLabor epidural analgesia is highly effective, but can be limited by slow onset and incomplete blockade. The administration of warmed, compared to room temperature, bupivacaine has resulted in more rapid onset epidural anesthesia. We hypothesized that the administration of bupivacaine with fentanyl at 37°C versus 20°C would result in improved initial and ongoing labor epidural analgesia.MethodsIn this prospective, randomized, doubled blinded study, 54 nulliparous, laboring women were randomized to receive epidural bupivacaine 0.125% with fentanyl 2 μg/mL (20 mL initial and 6 mL hourly boluses) at either 37°C or 20°C. Pain verbal rating scores (VRS), sensory level, oral temperature, and side effects were assessed after epidural loading (time 0), at 5, 10, 15, 20, 30, 60 min, and at hourly intervals. The primary outcome was the time to achieve initial satisfactory analgesia (VRS ⩽3). Secondary outcomes included ongoing quality of sensory blockade, body temperature and shivering.ResultsThere were no differences between groups in patient demographics, initial pain scores, cervical dilatation, body temperature or mode of delivery. Epidural bupivacaine at 37°C resulted in shorter mean (±SD) analgesic onset time (9.2 ± 4.7 vs. 16.0 ± 10.5 min, P = 0.005) and improved analgesia for the first 15 min after initial bolus (P = 0.001–0.03). Although patient temperature increased during the study (P < 0.01), there were no differences between the groups (P = 0.09). Six (24%) and 10 (40%) patients experienced shivering in the 37°C and 20°C groups, respectively (P = 0.23).ConclusionsThe administration of epidural 0.125% bupivacaine with fentanyl 2 μg/mL at 37°C versus 20°C resulted in more rapid onset and improved labor analgesia for the first 15 min. There was no evidence of improved ongoing labor analgesia or differences in side effects between groups.     

Preoperative use of gabapentin decreases the anesthetic and analgesic requirements in patients undergoing radical mastectomy

Background/aimGabapentin is an anticonvulsant drug that is safe and effective for the treatment of neuropathic pain syndrome, as well as postoperative pain with good results. This prospective randomized study was done to evaluate the effects of preoperative administration of oral gabapentin (1200 mg) on the intraoperative fentanyl and isoflurane consumption, postoperative analgesic requirements and postoperative pain in patients undergoing radical mastectomy.MethodsSixty ASA I and II patients were randomly allocated into two equal groups to receive oral gabapentin 1200 mg, 2 h before surgery (G group) or control (C group). General anesthesia was induced and maintained at bispectral index value between 40 and 60. During surgery the end-tidal isoflurane concentrations required to maintain adequate depth of anesthesia and the required incremental doses of intraoperative fentanyl were recorded. Postoperative pain was assessed using visual analogue scale (VAS) at rest for 24 h. Postoperatively, whenever visual analogue scale (VAS) was more than 5 or on patients’ demand, analgesia in both groups was provided with diclofenac sodium (1 mg/kg IM) or tramadol hydrochloride (1 mg/kg IV) as needed. VAS, analgesics requirements, and side-effects were assessed for 24 h postoperatively.ResultsIntraoperative fentanyl and postoperative analgesic consumption were significantly lower in G group than C group (P < 0.001). Patients in the G group had significantly lower end-tidal concentrations of isoflurane required to maintain adequate depth of anesthesia (P < 0.05). VAS was significantly lower in G group than C group at the first three measurement times (P < 0.01). The incidence of postoperative nausea and vomiting was significantly lower in G group than C group (30% versus 60% of patients, respectively, P < 0.05). The incidence of dizziness was significantly higher in the G group than C group (26% versus 3.3% of patients, respectively, P < 0.05).ConclusionGabapentin (1200 mg) administered orally 2 h before surgery decreased the intraoperative fentanyl and isoflurane consumption, postoperative analgesic requirements, postoperative pain, and the incidence of postoperative nausea and vomiting, but increased dizziness.     

Effect of primary versus revisional Roux-en-Y gastric bypass: inferior weight loss of revisional surgery after gastric banding

BackgroundLaparoscopic adjustable gastric banding is a popular and effective restrictive bariatric procedure. However, with longer follow-up, it has become clear that a considerable number of patients require revisional surgery, of which Roux-en-Y gastric bypass (RYGB) is the most commonly performed procedure. Studies that compared the outcomes of primary RYGB and revisional RYGB have not been conclusive. Our objective was to determine whether significant differences exist in the 1-year outcomes between primary RYGB (prim-RYGB) and revisional RYGB after laparoscopic adjustable gastric banding (rev-RYGB) at a major training hospital in The Netherlands.MethodsAll prim-RYGB and rev-RYGB procedures performed from 2007 to 2009 were analyzed. Data were collected regarding weight loss, hospitalization, operative time, postoperative complications, and co-morbidities.ResultsA total of 292 RYGB procedures were performed: 66 rev-RYGB and 226 prim-RYGB procedures. The operative time was significantly shorter in the prim-RYGB group (136.6 ± 37.5 versus 167.5 ± 40.6 min; P < .0001). No significant differences were found in hospitalization time (4.4 ± 1.7 versus 4.9 ± 2.4 d; P = .063) or complication rate (14.7% versus 15.2%; P = .962). No deaths occurred in either group. The number of patients with resolved diabetes and hypertension did not differ between the 2 groups (50.1% versus 23.1%; P = .116; and 40.7% versus 25.0%; P = .384, respectively). Weight loss was significantly greater in the prim-RYGB group in terms of excess weight loss (71.6% ± 20.8% versus 48.4% ± 26.8%; P < .0001), body mass index reduction (13.0 ± 3.8 versus 10.2 ± 5.6 kg/m²; P < .0001), absolute weight loss (37.4 ± 11.5 versus 29.3 ± 17.2 kg; P = .001), and percentage of weight loss (29.7% ± 8% versus 21.7% ± 11.5%; P < .0001).Conclusionrev-RYGB is a safe procedure with outcomes similar to those of prim-RYGB in terms of complication rate, hospitalization time, and effect on co-morbidity. Weight loss, however, was significantly less after rev-RYGB than after prim-RYGB.     

Pharmacokinetic variability of clarithromycin and differences in CYP3A4 activity in patients with cystic fibrosis

BackgroundTo investigate the correlation between CYP3A4/5 activity and clarithromycin metabolism, and between CYP3A activity and CYP3A genotype.MethodsThis is an open-label, prospective pharmacokinetic study evaluating CYP3A activity using The Erythromycin Breath Test. Eight blood samples were collected within 12 h after clarithromycin 500 mg was administered orally. The clarithromycin concentrations were measured by liquid chromatography–tandem mass spectrometry. AUC, Tmax and Cmax were calculated. Selected Single Nucleotide polymorphisms in CYP3A4/5 genes were assessed by PCR and single base extension.ResultsTwenty-one chronically infected patients were included. An 8-fold variation in the CYP3A4 activity, 10-fold variation in AUC for clarithromycin (median 881 μg/mL × min), and a 16-fold variation in Cmax for clarithromycin (median 3.4 μg/mL) were found. A linear correlation between the CYP3A4-activity and clarithromycin metabolism was demonstrated (P < 0.05).ConclusionThe large variation in the clarithromycin pharmacokinetics in cystic fibrosis patients may cause treatment failure. The Erythromycin Breath Test could be valuable in identifying cystic fibrosis patients in risk of treatment failure/drug toxicity.     

An Emergency EVAR Service Reduces Mortality in Ruptured Abdominal Aortic Aneurysms

ObjectivesThe aim of this study was to compare all in-hospital mortality for ruptured abdominal aortic aneurysms (rAAAs) before and after the establishment of an emergency EVAR (eEVAR) service.Design and methodsAn eEVAR service was established in January 2006, since when all patients presenting with rAAAs have been considered for endovascular repair. Data for all rAAAs presenting between January 2006 and December 2007 was prospectively collected (Group 1). This patient group was compared to those presenting with rAAA between January 2003 and December 2005 when eEVAR was not offered at our institution (Group 2). These records had also been collected prospectively and submitted to the National Vascular Database (NVD).ResultsA total of 50 rAAAs (17 eEVAR, 29 open repairs, 4 palliated) presented after the introduction of eEVAR (Group 1) and 71 in the historical Group 2 of which 54 underwent open repair and 17 were palliated. The total in-hospital mortality was significantly lower in Group 1 20% (eEVAR (n = 1), 6%: Open (n = 5), 17%: palliated (n = 4), 100%) when compared to Group 2 54% (Open (n = 21), 39%: palliated (n = 17), 100%) (p = 0.000001). Furthermore similar significant differences were seen in 30-day operative mortalities between the two groups 13% in Group 1 versus 39% in Group 2 (p = 0.0003). In addition the proportion of patients who were palliated has significantly decreased (8% Group 1 versus 24% Group 2, p = 0.01).ConclusionsThe establishment of an eEVAR service has significantly reduced in-hospital mortality for patients presenting with ruptured abdominal aortic aneurysms.