BM Group Research Articles

An observational study to evaluate the effect of different epidural analgesia regimens on dynamic pain scores in patients receiving epidural analgesia for postoperative pain relief after elective gynecological surgery.

Background and Aims:The primary measure of efficacy of any analgesic regimen is pain relief, but it is important to measure dynamic pain relief rather than pain relief at rest. Epidural analgesia is an effective technique for postoperative analgesia. The drug combinations given therein (local anesthetics with adjuvants such as opioids/alpha-2 agonists), however, remain a personal choice. The aim of this study was to evaluate dynamic pain scores in patients receiving different epidural analgesia regimens for postoperative pain relief after elective gynecological surgery used in our institution.Material and Methods:One hundred eighty-seven patients enrolled in this study received postoperatively either bupivacaine 0.125% + morphine 0.1 mg/mL (group BM) or bupivacaine 0.125% + fentanyl 2 μg/mL (group BF) or bupivacaine 0.125% + clonidine 1 μg/mL (group C1) or bupivacaine 0.125% + clonidine 2 μg/mL (group C2) by continuous epidural infusion @ 5 mL/h. Differences in dynamic pain scores (on coughing and mobilization), pain scores at rest, sensory and motor blockade, sedation scores, dry mouth, pruritus, nausea, and vomiting were recorded. Also duration of postoperative analgesia, epidural top-ups, requirement of rescue analgesic, and patient satisfaction were determined. All observations were carried out at 1, 2, 4, 8, and 12 h after surgery and then at 8 am, 12 noon, 4 pm, 8 pm on subsequent postoperative day till removal of epidural catheter (after 96 h).Results:There was no difference in demographic or hemodynamic profile among the four groups (P > 0.05). There was no statistically significant difference in pain scores at rest among the four groups but dynamic pain scores were found to be better in group C2 as compared to group BM, BF, and C1 at most of the time intervals although not statistically significant (P > 0.05). Requirement of rescue analgesics was lower in group BM and group C2 as compared to group BF and C1 (P < 0.01). Incidence of pruritus was 43.5% in group BM and 19% in group BF, while no patients in group C1 or C2 had pruritus. Mean postoperative nausea and vomiting (PONV) scores were higher in group BM and group BF as compared to group C1 and C2 (P < 0.001). Mean sedation scores were comparable in all four groups. Incidence of dry mouth was 22% in group C2 as compared to 11% in group C1, while no patients in group BM or BF had dry mouth. Patients in group C2 were more satisfied as compared to other three groups.Conclusions:Combination of clonidine 2 μg/mL to 0.125% bupivacaine @ 5 mL/h in combined spinal epidural provides better postoperative analgesia as compared to combination of bupivacaine with opioids with greater patient satisfaction and significantly reduced side effects.

Paravertebral block with morphine or dexmedetomidine as adjuvant to bupivacaine for post-operative analgesia in modified radical mastectomy: A prospective, randomised, double-blind study

Background and Aims:General anaesthesia (GA) is the standard technique and paravertebral block (PVB) is suggested as an ideal analgesic in patients undergoing modified radical mastectomy (MRM). This study assessed post-operative analgesic efficacy of morphine or dexmedetomidine as adjuvant to bupivacaine in PVB.Methods:Forty-five women (18–60 years) undergoing MRM ± axillary clearance received PVB with 20 ml bupivacaine 0.25% with morphine 3 mg (Group BM) or dexmedetomidine 1 μg/kg (Group BD) in this prospective, randomised, double-blind study. After confirming the onset of PVB, standardised GA induction sequence was used. Intra-operative consumption of fentanyl and propofol along with postoperative morphine and diclofenac consumption, numerical rating scores (NRS) for pain at rest and on movement, nausea and vomiting scores, sedation scores and time to rescue analgesic were recorded. Chi-square or Fisher's exact test and Kruskal–Wallis followed by Mann–Whitney U-test were applied as applicable.Results:The number of patients requiring morphine during first 2-h post-operatively was significantly lower (P = 0.006) in Group BM. The mean dose of morphine in Group BM (0.84 [2.41] mg) and Group BD (1.70 [1.84] mg) was comparable (P = 0.187). NRS for pain at rest and on movement was significantly lower in Group BM at 2, 6, 12 and 18 h. The duration of analgesia was significantly prolonged in Group BM (1019.8 [422.9] min) than in Group BD (263.7 [194.9] min) (P < 0.001).Conclusion:Morphine is superior adjuvant to bupivacaine in PVB for modified radical mastectomy than dexmedetomidine.

A randomized-controlled, double-blind study to evaluate the efficacy of caudal midazolam, ketamine and neostigmine as adjuvants to bupivacaine on postoperative analgesic in children undergoing lower abdominal surgery.

Background: Caudal epidural is the most commonly used technique for the management of postoperative pain in children. The aim of the present study was to assess and compare the efficacy of caudal bupivacaine as a postoperative analgesic alone or combined with midazolam, ketamine, and neostigmine in pediatric patients undergoing lower abdominal surgery. Methods: Eighty pediatric patients categorized under the American Society of Anesthesiologists Physical Status I and II Classification System, who have been scheduled to undergo lower abdominal surgery were randomly designated into four groups to receive caudal block with either 1 ml/kg of 0.25% caudal bupivacaine for group B, 1 ml/kg of 0.25% caudal bupivacaine mixed with 2 μg/kg neostigmine for group BN, 1 ml/kg of 0.25% caudal bupivacaine mixed with 0.5 mg/kg ketamine for group BK or 1 ml/kg of 0.25% caudal bupivacaine mixed with 50 mcg/kg midazolam for group BM. Postoperative analgesia was examined by a blinded anesthetist utilizing a Revised Faces Pain Scale. Consumption of the total amount of rescue analgesic each 24 h, postoperative time to requirement of the first dose and any adverse effects were noted. Results: The four groups were comparable as regards age, sex, weight, duration of surgery, heart rate, blood pressure and the time from induction of anesthesia to response to voice. The Revised Faces Pain Scale was 2.6±1.5 in group BN, 3.1±1.8 in group BM, 4.4±2.4 in group BK, and 5.6±1.3 in group B (p=0.005). Postoperative duration of analgesia was 433±68 min, 769±118 min, 1097±126 min and 1254±176 min in groups B, BK, BM and BN respectively (P=0.001). The dose of rescue analgesic within 24 h in group B was significantly higher than those of the other three groups (P<0.05). Conclusion: Addition of either neostigmine, midazolam, or ketamine to caudal bupivacaine extended analgesia time and decreased rescue analgesic compared to bupivacaine alone in children who underwent lower abdominal surgery. (www.actabiomedica.it)

Effects of Vitamin and Trace Element Supplementation on Weight Gain and Health of Calves Fed Raw or Pasteurized Waste Milk

The&#x0D; aim of the presented study is to investigate the effects of vitamin-mineral&#x0D; supplement on weight gain and health of dairy calves fed raw or pasteurized&#x0D; milk. The study was conducted on 40 calves from two different herds. Ten calves&#x0D; from herd A, received raw milk and 7.5 g of supplement twice daily (15g/calf/day)&#x0D; for 60 days (AM group); 10 other calves did not receive any supplement and were&#x0D; fed raw milk for 60 days (AC group).Ten calves from herd B (BM group), received&#x0D; 7.5 g of supplement twice daily (15g/calf/day) for 60 days mixed with&#x0D; pasteurized milk (72°C for 15 s). Calves in BC group (n:10) did not receive any&#x0D; supplement and calves in this group were fed with pasteurized milk for 60 days.&#x0D; Body weight of all calves were measured just after birth and on day 60 of the&#x0D; study when calves were weaned. Birth weights (kg±SEM) of groups AM, AC and BM,&#x0D; BC were 34.6±1.59, 34.6±1.68 and 36.4±2.51, 36.8±1.40 respectively. Weaning weights&#x0D; (kg±SEM) of groups AM, AC and BM, BC were 68.2±2.15, 65.9±1.89 and 81.5±3.21,&#x0D; 72.8±2.38 respectively. ADG (g±SEM) of groups AM, AC and BM, BC were calculated&#x0D; as 560±35, 522±25 and 768±30, 600±19 respectively. ADG and weaning weight of AM&#x0D; and AC was similar; however, ADG and weaning weight of BM was significantly&#x0D; higher (P&amp;lt;0.05) than ADG and weaning weight of BC. In conclusion, vitamin&#x0D; and trace element supplementation has beneficial effects on weight gain and&#x0D; health of dairy calves fed pasteurized waste milk.

Blue Corn Tortillas: Effects on Learning and Spatial Memory in Rats.

Consumption of pigmented corn has been associated with health benefits due to its flavonoid contents (mainly anthocyanins) and antioxidant ability. Therefore, the objective of this study was to determine the effect of blue corn tortilla (BM) consumption on memory and learning ability adult rats. Eighteen adult female rats were divided into three groups and fed for 38 consecutive days with commercial food (Control group) or the commercial food plus 6g/day of either blue corn (BM) or white corn (WM) tortillas. Memory and learning capabilities were assessed using Barnes's labyrinth at the end of the feeding period. Short-and long-term memory was improved in the BM group, showing that consumption of blue maize tortillas improves learning and memory capabilities in adult rats.

The anti-adiposity effect of bitter melon seed oil is solely attributed to its fatty acid components

BackgroundObesity is the leading chronic disease affecting people of all ages. The objective of this study was to optimize composition of a bitter melon seed oil (BMSO) product to maximize its anti-adiposity effect.MethodsBleaching oil, saponifiables and non-saponifiables were prepared from BMSO, with α-eleostearic acid (α-ESA) content in BMSO maintained in bleaching oil and saponifiables. C57BL/6 J mice were allocated into five groups (n = 10/group) to receive diet C [30% soybean oil (SBO)], BM [25% SBO + 5% BMSO], BMS, BMNS or BMD. For the three latter diets, saponifiables (hydrolyzed fatty acids from BMSO), non-saponifiables (excluding fatty acids from BMSO) or bleaching oil (excluding pigments from BMSO), respectively, were added in amount equivalent to their content in 5% BMSO and SBO was added to bring total fat to 30%. After 14 wk., indices associated with adiposity and safety, as well as lipid metabolic signaling in white adipose tissue (WAT), were measured.ResultsThe body fat percentage of mice in group BM, BMS, BMNS, and BMD were 90 ± 26, 76 ± 21, 115 ± 30 and 95 ± 17% of that in group C. Based on body fat percentage and plasma leptin concentrations, an anti-adiposity effect was evident in groups BM, BMS and BMD (greatest effect in BMS). Histologically, inguinal fat had smaller adipocytes in groups BM, BMS and BMD (P < 0.05), but not in group BMNS, relative to group C. There were no differences among groups in blood pressure or heart rate. Moreover, Sirt1 mRNA levels in inguinal fat were significantly greater in groups BM, BMS and BMD than group C.ConclusionWe concluded that the anti-adiposity function of BMSO was solely attributed to the fatty acid fraction, with the free fatty acid form having the greatest effect.

A comparative study of intrathecal nonopioid adjuvants to hyperbaric bupivacaine for spinal anaesthesia

Background: Intrathecal drugs when used as adjuvant to spinal anaesthesia produce substantial anti-nociception and potentiate analgesia of bupivacaine. This study was planned to evaluate the effects of intrathecal non opioid drugs-clonidine, midazolam, neostigmine and magnesium sulphate on duration of analgesia, characteristics of SA and hemodynamic stability when added to 0.5% hyperbaric bupivacaine for spinal anaesthesia.Methods: In this randomized, prospective, double blind study, 100 ASA physical status I and II adults patients posted for elective lower abdominal surgery were divided into 4 groups (n=25). Group BN received preservative free neostigmine 25µg, group BMG received Mgso4 50mg, group BC received clonidine 30µg and BM received midazolam 2mg with 15mg hyperbaric bupivacaine. Duration of postoperative analgesia, effect on onset and duration of sensory and motor block, incidence of side effects was noted. Continuous variables were compared using one way Analysis of Variance (ANOVA).Results: The duration of postoperative analgesia was significantly prolonged in BM group 391.64 (132.98) minutes, followed by BN group 308.76 (127.40), BC group 296.60 (52.77) and BMG group 252.2 (86.76). The numbers of analgesic doses in 24 hours were significantly less in BM group. One patient required additional analgesia in BM group as against 40%, 36% and 64% in BN, BC, BMG group respectively. The duration of sensory block was significantly prolonged in group BM followed by group BC and BN.Conclusions: Intrathecal midazolam provides superior analgesia without clinically relevant side effects. The onset of analgesia was rapid and duration prolonged with intrathecal midazolam followed by neostigmine and clonidine.

English

60 patients of ASA undergoing upper limb surgeries were randomly assigned into two groups, Group BM (midazolam) and Group B (Bupivacaine) Surgery was done under supraclavicular approach of brachial plexus blockade. The Patients in Group BM received 30ml of 0.375% bupivacaine 5μ/kg midazolam and In group B received 30 ml of 0.375% of bupivacaine. Parameters observed were time of onset of sensory block and motor block, duration of motor blockade, duration of sensory block analgesic, duration of analgesia, sedation score, Haemodynamic and side effects. Study shows that On addition of midazolam to local anaesthetic solution there is difference between the onset of sensory block and onset of motor blockade to bupivacaine 1. On addition of midazolam to local anaesthetic solution significantly prolongs the duration of analgesia in 15-18 hours compared to bupivacaine group which is 8-16 hours. 2. Addition of midazolam to local anaesthetic solution increases the duration of motor blockade by 7-9 hours compared to bupivacaine which is 5-7 hours. 3. On addition of midazolam to local anaesthetic solution increases the duration of sensory block 15 hours compared to bupivacaine which is 5-9 hours. CONCLUSION: The addition of midazolam to local anaesthetic solution in supraclavicular approach to brachial plexus, a) Produces significantly faster onset of sensory & motor blockade. b) Prolongs the duration of sensory & motor blockade and duration of analgesia.

The influence of breastfeeding in breast-fed infants with atopic dermatitis.

The aim of this study was to evaluate whether breastfeeding should be discontinued for exclusively breast-fed infants with atopic dermatitis (AD). Eighty-seven exclusively breast-fed infants with AD were enrolled in a prospective observational study. The infants were divided into 3 groups: breastfeeding only (BM group), partial breastfeeding and partial partially hydrolyzed whey formula (pHF-W) (Partial group) and pHF-W only (DC group). The extent and severity of AD were evaluated with the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) index at enrollment and 3 and 6 months later. There were no significant differences in parental atopy history, PO-SCORAD scores, and medication scores at baseline. At month 3 and 6, the PO-SCORAD scores were significantly decreased in all groups. PO-SCORAD scores at month 3 and 6 and at the last time point when topical corticosteroids were given were significantly different among the groups. Stepwise multiple linear regression analysis showed that baseline PO-SCORAD scores and stopping breastfeeding were significantly associated with month 3 PO-SCORAD scores (p<0.001), after adjusting for sex, age, baseline medication scores, partial breastfeeding and parental atopy history. In addition to baseline PO-SCORAD scores and stopping breastfeeding, partial breastfeeding was significantly associated with month 6 PO-SCORAD scores. Long-term follow-up showed that only stopping breastfeeding was significantly associated with the last time point when topical corticosteroids were given (p=0.014). For exclusively breast-fed infants with AD, discontinuing breastfeeding and shifting to pHF-W might help to improve symptoms and shorten the duration of AD regardless of sex, age and parental atopy history.

Donor-to-Recipient ABO Mismatch Does Not Impact Outcomes of Allogeneic Hematopoietic Cell Transplantation Regardless of Graft Source

The impact of ABO mismatch has been studied on various hematopoietic cell transplant (HCT) outcomes, including neutrophil and platelet engraftment, pure red cell aplasia, acute and chronic graft-versus-host disease (GVHD), nonrelapse mortality (NRM), and overall survival (OS). Yet conflicting results have been reported. However, the impact of ABO mismatch on transplant outcomes with various graft types has not been carefully investigated. We analyzed the impact of various graft sources and type of ABO mismatch on transplant outcomes for 1502 patients who underwent HCT at the University of Minnesota between 2000 and 2014: 312 receiving marrow (BM), 475 filgrastim-mobilized blood (peripheral blood stem cell [PBSC]), and 715 umbilical cord blood (UCB) grafts. Neutrophil engraftment by day 28 was marginally less frequent in the bidirectional ABO mismatched transplants receiving UCB, whereas ABO matching had no influence on engraftment in the BM or PBSC cohorts. ABO mismatch led to no significant differences in platelet engraftment irrespective of stem cell source. We observed a modest but not significantly lower incidence of grades II/IV acute GVHD in the bidirectional ABO mismatched transplants in the UCB and the PBSC cohorts but not in the BM group. We found a higher incidence of chronic GVHD in the PBSC group, but it was not significantly lower in the minor ABO mismatched transplants. The incidence of chronic GVHD was similar in the major ABO mismatched transplants receiving BM. We found no significant difference in the OS and NRM between ABO matched and ABO mismatched transplants within each of the 3 graft source groups. Multivariable analysis adjusting for other relevant factors confirmed that ABO match status did not significantly influence the outcomes of either engraftment, acute or chronic GVHD or NRM. We conclude that ABO mismatch does not influence the outcomes of allogeneic HCT, regardless of stem cell source.

Is the Use of Spreaders an Accurate Method for Ligament Balancing?

BackgroundTo analyze 2 methods of manual spreader gap assessment accuracy, visual vs blinded, compared with a controlled tensioner in total knee arthroplasty. MethodsTwenty-two fresh frozen cadaver knees were used to perform total knee arthroplasty by 22 surgeons. Extension and flexion gaps were measured with empirical manual force application with spreaders in 2 different manners: (1) surgeons were blinded to gap geometry formation—blind method group (BM) and (2) surgeons viewed them—viewing method group (VM). A tensioner was used to measure the corresponding ligament tension applied during spreader measurements and to measure the extension and flexion gaps with standard force of 100 and 80 N (tensioner method [TM]) in each femorotibial compartment. ResultsAll measurements with spreaders (VM and BM) presented extension and flexion gaps oversized and asymmetric (P < .0001), when compared with the same gaps measured with the tensioner. Approximately 63% (P = <0.001) and 77.3% (P = .161) of the VM group and 68.2% (P = .018) and 77.3% (P = .161) of the BM group demonstrated asymmetry for extension and flexion gaps up to 3 mm to the TM. Gaps measured in the VM group presented results with slightly less oversizing and asymmetries than the measurements in the BM group compared with TM, although significantly different (P < .0001). ConclusionThe assessment of extension and flexion gaps with empirical manual applied force spreaders produced oversized and asymmetric gaps compared with the use of tensioner. No visual influence was observed during the spreader applied empirical manual force compared with the blinded assessment.

Comparison of clinical effects of epidural levobupivacaine morphine versus bupivacaine morphine in dogs undergoing elective pelvic limb surgery

ObjectiveTo evaluate the efficacy, in terms of the amount of rescue analgesia required, and the clinical usefulness of epidural injection of morphine with bupivacaine or levobupivacaine for elective pelvic limb surgery in dogs during a 24-hour perioperative period. Study designProspective, blinded, randomized clinical study. AnimalsA group of 26 dogs weighing 31.7 ± 14.2 (mean ± standard deviation) kg and aged 54 ± 36 months. MethodsAll dogs were premedicated with methadone intravenously (0.2 mg kg–1) and anaesthesia induced with diazepam (0.2 mg kg–1) and propofol intravenously to effect. After induction of anaesthesia, dogs randomly received a lumbosacral epidural injection of morphine 0.1 mg kg–1 with either levobupivacaine 0.5% (1 mg kg–1; group LevoBM) or bupivacaine 0.5% (1 mg kg–1; group BM). Cardiovascular, respiratory and temperature values were recorded during the intra- and postoperative period. A visual analogue scale, subjective pain scale, sedation scale and the short form of the Glasgow pain scale were assessed every 6 hours after epidural injection during 24 hours. The ability to stand and walk, neurological deficits and other side effects were assessed at the same time points. The amount of rescue analgesia (sufentanil intraoperatively and methadone postoperatively) was recorded. ResultsNo statistically significant differences were found between groups for any of the recorded data, with the exception of the incidence of spontaneous urination and postoperative rescue analgesia requirement. In group LevoBM four dogs spontaneously urinated at recovery while none of the dogs in group BM did (p = 0.03) and seven dogs of group LevoBM required postoperative rescue analgesia versus none of the dogs in the BM group (p = 0.005). Conclusionsand clinical relevance Epidural LevoBM is a suitable alternative to BM in healthy dogs during elective pelvic limb surgery. Epidural BM produced more urinary retention but better pain control compared to the same concentration and dose of LevoBM in dogs.

Comparative study of caudal clonidine and midazolam added to bupivacaine during infra-umbilical surgeries in children.

Background and Aims:Caudal analgesia is a good, reliable, and easy method to provide intraoperative and postoperative analgesia for infra-umbilical surgeries in children. Many additives are being used in combination with local anesthetics in caudal block to prolong the postoperative analgesia (clonidine, midazolam, ketamine, fentanyl, and dexmedetomidine). The purpose of this study was to compare the intraoperative hemodynamics, postoperative analgesia, postoperative rescue analgesic requirement, postoperative sedation and side-effects of clonidine and midazolam used as adjuvants to bupivacaine for caudal analgesia.Material and Methods:Following approval from Institutional Ethical Research Committee, 75 American Society of Anesthesiologists I and II patients aged between 1 and 7 years undergoing various elective infra-umbilical surgical procedures were included in this study. The patients were randomly allocated into three groups of 25 patients each. Group B received 1 ml/kg 0.25% bupivacaine in normal saline, Group BC received 1 ml/kg 0.25% bupivacaine + 1 μg/kg clonidine in normal saline, and Group BM received 1ml/kg 0.25% bupivacaine + 30 μg/kg midazolam in normal saline. The various parameters studied were intraoperative hemodynamic changes, duration of postoperative analgesia, postoperative sedation, postoperative analgesic requirement, and incidence of side-effects.Results:All the groups were similar with respect to patient and block characteristics. The hemodynamic parameters before and after administering caudal analgesia were also comparable. The mean duration of analgesia was 724.80 ± 60.29 min in Group BC, 605.40 ± 82.37 min in Group BM and 295.00 ± 41.78 min in Group B. Thus, the duration of analgesia was significantly prolonged in Group BC compared to Groups BM and B. The FLACC pain score was higher in Group B at the end of 4th, 8th and 12th h compared with Group BC and Group BM. Furthermore at the end of 12th h, pain scores were significantly higher in Group BM compared to Group BC. Only 1 child in Group BC received three rescue medications compared to 15 (60%) children in Group B and 7 (28%) children in Group BM. None of the groups were treated for bradycardia or hypotension and no significant sedation was noted.Conclusion:This study showed that the addition of both clonidine (1 μg/kg) and midazolam (30 μg/kg) with bupivacaine administered caudally significantly increase the duration of postoperative analgesia with minimal side-effects in children. The use of clonidine as an additive to bupivacaine in caudal epidural is a superior choice to midazolam as it reduces the demand of postoperative rescue analgesics significantly.

Comparison of Bupivacaine Plus Magnesium Sulfate and Ropivacaine Plus Magnesium Sulfate Infiltration for Postoperative Analgesia in Patients Undergoing Lumbar Laminectomy: A Randomized Double-blinded Study.

Aim:The objective of this study was to assess and compare the analgesic duration of local infiltration of bupivacaine plus magnesium sulfate and ropivacaine plus magnesium sulfate for postoperative analgesia in patients undergoing lumbar laminectomy.Study Design:A randomized, prospective, double-blinded single hospital, comparative study.Methods:Sixty adult patients of the American Society of Anesthesiologists physical Status I and II were randomly allocated into two Groups BM and RM, comprising 30 and 31 patients. Postlumbar laminectomy, the study drug was locally infiltrated into the paravertebral muscles on either side before skin closure. Group BM was given 20 ml of 0.25% bupivacaine combined with 500 mg of magnesium sulfate (constituted with normal saline [NS]), and Group RM was given 20 ml of 0.25% ropivacaine combined with 500 mg of magnesium sulfate (constituted with NS). Postoperative visual analog scale pain score was assessed hourly for the first 24 h postoperatively. Duration of postoperative analgesia, rescue analgesia consumption and side effects were also recorded.Statistical Analysis:Comparison of data between the groups was done with SPSS 21.0© using independent t-test, Chi-square test, and Mann–Whitney U-test accordingly. P<0.05 was considered statistically significant.Results:Time to first analgesic consumption was significantly longer in Group BM (7.3 ± 0.46 h) compared to Group RM (6.6 ± 0.69 h) (P < 0.05). The consumption of nalbuphine rescue analgesic was significantly higher in Group RM (15.33 ± 5.07 mg) compared to Group BM (12 ± 4.07 mg) (P < 0.05).Conclusion:Wound infiltration with bupivacaine and magnesium sulfate compared to ropivacaine and magnesium sulfate provided longer duration of postoperative analgesia and significantly reduced postoperative opioid consumption in patients undergoing lumbar laminectomy.

Comparison of intra-articular analgesics in arthroscopic anterior cruciate ligament reconstruction surgeries: A randomized controlled trial.

Background and Aims:Arthroscopic anterior cruciate ligament reconstruction (ACLR) is one of the most common knee surgeries done worldwide today. It involves immense pain at sites of graft harvest, tibial, and femoral tunnels, thereby delaying recovery and increased patient morbidity, and delayed rehabilitation. Various drugs and combination of drugs administered intra-articularly have been studied for analgesic efficacy. Our study gives an insight if there is any added advantage of additives morphine or clonidine to bupivacaine when compared to administering bupivacaine alone.Material and Methods:After obtaining the Institute Ethics Committee approval, ninety American Society of Anesthesiology I-II patients undergoing arthroscopic ACLR under spinal anesthesia were randomly assigned to one of three groups (Group B – bupivacaine alone 0.25%, Group BM – bupivacaine 0.25% with morphine 5 mg, Group BC – bupivacaine 0.25% with clonidine 150 mcg). At the end of procedure, 20 mL of the respective drug was administered intra-articularly and postoperative time duration to rescue analgesia, 24 h analgesic requirement, visual analog scale (VAS) score findings at rest and on movement were observed.Results:The mean duration of time to request for first rescue analgesia in minutes was significantly longer in Group BC 341.55 (103.66 SD) with P < 0.001. The VAS scores at that time point were least in Group BM 6.1 (1.7 SD), but not statistically significant. The 24 h analgesic consumption was least in Group B 2.24 (0.79 SD), but not statistically significant.Conclusion:Combination of bupivacaine and clonidine administered intra-articularly provided a longer duration of analgesia though the quality of analgesia was comparable between the three groups.

Role of Cell Source and Graft Composition in Haploidentical Transplantation Using Post-Transplant Cyclophosphamide

Introduction: Cell source and graft composition are known to have a prognostic role in allogeneic hematopoietic cell transplant (HCT). Currently, there are no data in the setting of haploidentical-HCT with post-transplant cyclophosphamide (PT-Cy).Patients and methods: One-hundred patients undergoing haplo-HCT with PT-Cy from Sept 2011 to Nov 2015 were included in this multicenter retrospective analysis.Bone marrow (BM) was used as graft source in 25 patients and peripheral blood stem cell (PBSC) in 75. The two groups (BM vs PBSC) were similar in terms of age, Disease Risk Index (DRI) and HCT-CI. The only differences were on disease type (lymphoid malignancies 76% vs 57%, p=0.02) and conditioning regimen (myeloablative: 100% versus 30%, p<0.01).Graft cellular subsets analysis was performed by means of flow cytometry (CD34, CD3, CD4, CD8, CD56, CD19, CD38, CD31, CD25, CD45RA, CD95, CD127, CCR4, CCR6, CCR7). Overall Survival (OS) and Progression Free Survival (PFS) were performed with Kaplan-Meier analysis. Acute GVHD, chronic GVHD, Non-Relapse Mortality (NRM) and Relapse Incidence/Progression of disease (RI/POD) were obtained with competing risk analysis.Results: For the whole cohort, neutrophil and platelet engraftment cumulative incidences at day +30 were 97% (95% CI: 91-99) and 64% (95% CI: 53-73), with no differences between BM or PBSC. Grade II-IV and grade III-IV aGVHD cumulative incidences at day +100 were 36% (95% CI: 26-48) and 10% (95%CI: 5-18), respectively. Acute GVHD cumulative incidence was significantly lower for BM grafts [16% (95% CI: 5-33) vs 43% (95% CI: 31-54), p=0.02], but no differences were observed regarding grade III-IV acute GVHD [8% (CI 95%: 1-24) vs 11% (CI 95%: 5-20), p=0.73]. Chronic GVHD cumulative incidence at 18 months was 23% (95%CI: 15-32) with no difference between BM or PBSC. With a median follow up of 16.5 months (range 0.8 - 40.6), the 18-months PFS and OS were 43% (95%CI: 32-54) and 63% (95% CI: 52-73), respectively. NRM and RI/POD at 18 months were 18% (95%CI: 11-26) and 38% (95%CI: 27-49).Multivariable analysis was performed using patient (age, gender, HCT-CI, DRI) and transplant characteristics (donor gender, donor-recipient relation, graft source). A DRI>1 was the only factor associated with higher RI/POD (HR 3.45, 95% CI: 1.4-8.2, p<0.01), lower PFS (HR 2.77, 95%CI: 1.4-5.3, p<0.01), and lower OS (HR 2.33, 95%CI: 1.1-4.9, p=0.02). Graft source did not influence survival outcomes.Graft cell composition analysis was performed separately for BM and PBSC cohorts. For the BM group, univariable analysis showed that CD4 graft count ≥20x10^6/kg was associated with a prolonged PFS [60% (95%CI: 28-81) vs 0%, p<0.01] (fig. 1), a trend toward a decreased NRM [0% vs 27% (95%CI: 5-56), p=0.05] and a prolonged OS [92%(95%CI: 57-99) vs 58% (95%CI:27-80), p=0.05]. Among the CD4 subsets analyzed (activated, central memory, effector, effector memory, memory stem cells, regulatory, Th17), naive T cells ≥8.5x10^6/kg (CD3+/CD8-/CD4+/CCR7+/CD45RA+/CD95-) and recent thymic emigrants ≥6.9x10^6/kg (median) (RTEs, CD4+/CD31+/CD45RA+) were the only phenotypes associated with a better PFS and OS (p=0.02 and p=0.04 respectively). For the PBSC group, CD8 graft count ≥ 75 x10^6/kg (median) was associated with a lower NRM [3% (95%CI: 0-12) vs 16% (95%CI:6-30), p=0.01]. No associations were found regarding graft cell composition and incidence of acute or chronic GVHD for both BM and PBSC groups.Conclusions: In our retrospective analysis, we did not observe significant differences in survival outcomes based on graft source. Patients receiving BM grafts developed fewer grade II-IV aGVHD, but grade III-IV aGVHD incidence was similar between the two groups.For the BM group, a higher CD4 count was predictive of better PFS, TRM and OS, as reported with standard GVHD prophylaxis and matched donors (Waller EK, J Clin Oncol 2014. 32: 2365-2372). Interestingly, of the CD4 population, only naive T cells and RTEs were associated with an improved PFS and OS. A protective effect of CD8 cell count was observed in the PBSC group. This is similar to the non PT-Cy setting where higher CD8 cells are associated with better survival outcomes (Reshef R, J Clin Oncol 2015). These data should be validated in a prospective analysis to guide the choice of cell source in the haplo PT-Cy setting. [Display omitted] DisclosuresCorradini:Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Roche: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; Servier: Honoraria; Gilead: Honoraria; Takeda: Consultancy.

Host Interleukin 6 and Indoleamine 2,3 Dioxygenase Regulate Inflammation in the Brain during Graft Versus Host Disease

Graft versus host disease (GVHD) commonly induces pathological damage in peripheral target organs such as the skin, liver and gastrointestinal tract leading to well characterized organ-specific clinical manifestations. A number of studies, however, have shown that patients with GVHD can also have behavioral and mood alterations that can affect overall cognitive function and lead to significant impairments in quality of life. The extent to which GVHD contributes to cognitive dysfunction and induces inflammation within the central nervous system (CNS), however, has not been critically examined. To address this question, we conducted studies using two well-defined murine GVHD models [C57BL/6(H-2b)→Balb/c (H-2d) and B10.BR(H-2k)→B6 (H-2b)]. We observed that there was a significant increase in the number of donor-derived CD4+ and CD8+ T cells in the brains of GVHD recipients early (days 7 -14) and late (day 42) post transplantation compared to BM controls. Histological studies revealed activated microglial cells and CD3+ T cell infiltration in the periventricular regions of brains in GVHD recipients that were not present in BM animals. Real time q-PCR analysis also demonstrated significant increases in IFN-γ, TNF-α, and IL-6 mRNA expression indicative of a proinflammatory state. Notably, GVHD animals exhibited behavioral changes in the forced swim test and elevated plus maze which are validated assays of stress coping and anxiety, respectively. Since IL-6, in particular, plays a pivotal role in GVHD pathogenesis in murine models and humans, we examined whether blockade of IL-6 signaling altered neuroinflammation. Animals treated with an anti-IL-6R antibody had a significant reduction in the number of donor-derived CD4+ and CD8+T cells in the brain compared to isotype control-treated mice. Anti-IL-6R treatment of GVHD mice also resulted in significant reductions in IFN-γ, TNF-α, and IL-6 mRNA and normalized behavior in the forced swim test, indicative of a decreased inflammatory response. Since IL-6 is produced by a wide variety of cells, including microglial and T cells, both donor and recipient cells have the potential to modulate GVHD severity within the CNS. To define whether donor or host IL-6 production was most critical for inducing neuroinflammation, experiments were conducted employing IL-6-/- mice as either donors or recipients. Whereas the absence of IL-6 in donor-derived cells had no impact on the degree of inflammation within the CNS, recipient animals that lacked IL-6 had a significant decrease in the number of donor-derived T cells which accumulated in the brain as well as a marked reduction in inflammatory cytokines, indicating that host IL-6 production was critical. To define the downstream pathways of IL-6-mediated CNS inflammation, we examined the role of indoleamine 2,3-dioxygenase (IDO) since IL-6 has been shown to upregulate IDO-1 expression under inflammatory conditions. We observed that IDO-1 mRNA levels were significantly increased in the brains of GVHD animals, and that blockade of IL-6 signaling resulted in a marked decrease in IDO mRNA levels. Additionally, transplantation studies using IDO-/- mice revealed that host, but not donor, IDO production was required for maximal inflammatory effects. Serotoninergic projections to the prefrontal cortex (PFC), in particular, are sensitive to inflammation and contribute to stress coping behavior. Therefore, to further interrogate this pathway, we performed quantitative mass spectrometry of brain extracts from the PFC. We found that tryptophan and 5HT concentrations were not different between BM and GVHD groups. However, there was an increase in the IDO product, kynurenic acid, in GVHD recipients consistent with an increase in brain IDO expression. To provide additional support for the premise that IL-6 effects were mediated through the IDO pathway, recipient mice were treated with either 1-methyltryptophan (1-MT), a completive inhibitor of IDO, or a vehicle control. GVHD mice treated with 1-MT had decreased accumulation of T cells in the brain and normal behavior in the forced swim test, demonstrating that inhibition of IDO abrogated CNS inflammation and behavioral changes in the presence of intact IL-6 signaling. In summary, these studies demonstrate that host IL-6 and IDO regulate inflammation and adversely impact behavioral function within the brain during GVHD through the tryptophan metabolic pathway. DisclosuresNo relevant conflicts of interest to declare.

Upregulation of (C-X-C motif) Ligand 13 (CXCL13) Attenuates Morphine Analgesia in Rats with Cancer-Induced Bone Pain.

BackgroundThe aim of this study was to investigate the role of chemokine (C-X-C motif) ligand 13 (CXCL13) in morphine tolerance in rats with cancer-induced bone pain (CIBP).Material/MethodsWe established a rat CIBP model and a rat CIBP-morphine tolerance (BM) model. BM rats were intrathecally administered rmCXCL13, neutralizing anti-CXCL13, and normal saline, while the control group rats underwent a sham operation and were injected with normal saline. The morphine analgesia was assessed by measuring mechanical withdrawal threshold (MWT) and mechanical withdrawal duration (MWD) at various time points. The co-expressions of CXCL13 and NeuN were measured by immunofluorescence double-staining. CXCL13 protein and mRNA expressions were detected by Western blot and quantitative real-time polymerase chain reaction (RT-qPCR), respectively.ResultsCompared to the sham-operation (S) group, the BM group showed obviously decreased MWT and increased MWD on Day 9 after CIBP, but obviously increased MWT and decreased MWD on Day 3 after morphine administration; subsequently, the MWT was decreased and MWD was increased (all P<0.05). In comparison with the S+saline group, increased MWT and decreased MWD were observed in BM rats on Day 3 after anti-CXCL13 administration, and obviously decreased MWT and increased MWD were found in BM rats on Day 3 after rmCXCL13 administration (all P<0.05).ConclusionsUp-regulated CXCL13 has a negative role in morphine analgesia in relief of CIBP, which may provide a new target for the management of CIBP.

Assessment of dry eye in a GVHD murine model: Approximation through tear osmolarity measurement

Dry eye disease is one of the most frequent pathological events that take place in the course of the graft versus host disease (GVHD), and is the main cause of deterioration in quality of life for patients. Thus, demonstration of dry eye signs in murine models of oGVHD is crucial for the validation of these models for the study of the disease. Given the increasing evidence that tear osmolarity is an important player of dry eye disease, our purpose in this study was to validate the use of a reliable method to assess tear osmolarity in mice: the electrical impedance method. Then, we wanted to test its utility with an oGVHD model. Tear volume assessment was also performed, using the phenol red thread test. We found differences in tear osmolarity in mice that received a transplant with cells from bone marrow and spleen (the GVHD group) when compared with mice that only received bone marrow cells (the BM group) at day 7 (362 ± 8 mOsm/l and 345 ± 9 mOsm/l respectively; P < 0.01) and day 21 (348 ± 19 mOsm/l vs. 326 ± 15 mOsm/l; P < 0.05). We found also differences in tear volume at day 14 (2.30 ± 0.61 mm in oGVHD group and 2.89 ± 0.62 mm in BM group; P = 0.06) and at day 21 (2.10 ± 0.30 mm in oGVHD group and 2.89 ± 0.32 mm in BM group; P < 0.01). Besides this, we observed reduction in epithelial thickness between the GVHD and BM groups (37.0 ± 6.2 μm and 43.6 ± 3.3 μm respectively; P < 0.05). These data show the usefulness of the electrical impedance method to measure tear osmolarity in mice. We can also conclude that this oGVHD model mimics the tear film alterations found in human dry eye disease, what contributes to give relevance to this model for the study of GVHD.

Comparison of the effect of two types of whole mushroom (Agaricus bisporus) powders on intestinal fermentation in rats

The effects of two types of mushroom (Agaricus bisporus; white, WM; brown, BM) powders on intestinal fermentation in rats were investigated in terms of the physical characteristics of animals and by bacterial and HPLC analyses of cecal contents. Short-chain fatty acid levels were found to be significantly higher in the WM group than in the BM and the control (CN) groups; coliform bacteria levels in the BM group were significantly lower than those in the CN group, with the WM group inducing an apparent but insignificant decrease in coliforms. Anaerobe levels in the WM group were significantly higher than those in the CN group and, compared with the CN group, the BM and WM groups exhibited significantly increased feces weight and cecum weight, respectively. These results indicate that the mushroom powders, and in particular the WM powder, have beneficial effects on the intestinal environment in rats.