RD Group Research Articles

Linking Differences in Eating Behavior with Appetitive Hormones in Women

Abstract Objectives Examine and compare the hormones related to satiety in women identified as 1) restrained + disinhibited eaters, 2) restrained, non-disinhibited eaters, or 3) unrestrained, non-disinhibited eaters. We hypothesized restrained eaters with disinhibition would have a different pattern of appetitive hormones involved in food intake regulation. Methods 178 women from a cross-sectional study completed the three factor eating questionnaire (TFEQ), and were classified as restrained + disinhibited eaters (RD, n = 38), restrained, non-disinhibited eaters (R, n = 52), or unrestrained, non-disinhibited eaters (LL, n = 88). Women fasted for 12 h prior to baseline blood collection, and postprandial blood was collected after a meal challenge at 30 min, 3 h, and 6 h. Data were evaluated for outliers and missingness, and transformed and imputed using multivariate normal imputation. Differences in glucose, insulin and ghrelin were analyzed using a linear mixed model comparing groups. Time to peak and nadir for glucose, insulin and ghrelin were calculated from response curves. Chi square tests of proportions were used to determine whether the distribution of participants in the three groups were different in their times to peak and nadir. Results There were no significant differences between groups in ghrelin or insulin concentrations over time. However, overall glucose levels in RD were significantly lower than R and LL groups (P = 0.05 and P = 0.03, respectively). Chi-squared tests indicated that a greater proportion of women in the RD group reached peak glucose at 3 h, compared to women in R and LL with peak glucose occurring at 30 min (P = 0.04). Glucose nadir displayed a bimodal distribution in R, with more women at baseline and 3 h compared to RD and LL (P = 0.05). Ghrelin nadir was reached at 3 h for more participants in RD and LL, but occurred later at 6 h in more participants in R (P = 0.04). Conclusions Dietary restraint and disinhibition are associated with circulating glucose and ghrelin concentrations; however, prospective research is needed to determine if there is a causal relationship. Funding Sources USDA CRIS 2032-51530-022, 2032-51530-025, and 2032-51530-026-00-D, and a grant from Arla Foods Inc.

Effects of Long-Term High-Fat Diet and Its Reversal on Lipids and Lipoproteins Composition in Thoracic Duct Lymph in Pigs.

BackgroundThis study was carried out to evaluate the effects of a long-term high-fat diet on lipids and lipoproteins composition in thoracic duct lymph in pigs.Material/MethodsWe examined lymph taken from the thoracic duct from 24 female white sharp-ear pigs, divided into 3 experimental groups fed different diets for 12 months: (a) the control group, fed the standard balanced diet; (b) the HFD group, fed an unbalanced, high-fat diet, and (c) the reversal diet group (RD), fed an unbalanced, high-fat diet for 9 months and then a standard balanced diet for 3 months.ResultsLymph analysis after 12 months of fixed diets revealed significantly higher concentration of proteins in the HFD group in comparison to the control and RD groups. Examination of lymph lipoproteins fractions showed that the high-fat diet in the HFD group in comparison to control group caused an increase in cholesterol, phospholipids, and proteins content within HDL and chylomicrons. There were also more proteins within HDL in the HFD group in comparison to the RD group and more triglycerides within chylomicrons in the HFD group in comparison to the control group.ConclusionA long-term high-fat diet resulted in changed structure of HDL and chylomicrons in the thoracic duct lymph. Alterations in HDL composition suggest that a high-fat diet enhances reverses cholesterol transport. Changes in chylomicrons structure show the adaptation to more intense transport of dietary fat from the intestine to the liver under the influence of a high-fat diet. Reversal to a standard balanced diet had the opposite effects.

Approach to sexuality and sexual dysfunction by reproductive doctors in France

Summary Numerous studies have examined the negative impact of medically assisted reproduction (MAR) on patients’ sex lives. It appears necessary to question patients and sometimes to counsel them about management for their sexual and reproductive health. In this study prospective, quantitative, multicenter trial conducted from December 2018 through February 2019, we contacted the offices of all clinical MAR centers registered with the Agence de la Biomedecine (Biomedical Agency) to obtain a list of email addresses of the doctors working there and sent them questionnaires. We received 171 responses. The respondents were very predominantly women (89%), and their median age was 34 years (range: 28–64). Overall, 56% always discussed sexual function during their first consultation, 30% often, and 14% sometimes. We compared two groups: the “regular discussion” (RD) group, which included the doctors (n = 147) who responded “always” and “often”. The “occasional discussion” (OD) group included those (n = 24) who responded “sometimes”. The RD group discussed scheduling sexual relations less often than the OD group (P = 0.029). The RD and OD groups differed significantly in their rates of questions about the frequency of sexual relations (P = 0.04) and about problems of penetration (P = 0.025) and desire (P = 0.041); the RD group asked more often about all of these topics. In the RD group, 37% of the respondents had a sex therapist working at their center, and in the OD group, 21%, while respectively 9% and 17% did not know to whom or where to refer these patients, and 93% and 75% thought a sex therapist with expertise in MAR would be useful at their center. This study shows deficiencies in the management of sexual dysfunctions in MAR patients. Some actions that might improve the situation include: the creation of a directory of sex therapists, the creation of job lines at MAR centers for sex therapists specialized in this field, and the development of patient brochures and questionnaires.

Ultrasound-Guided Transversus Abdominis Plane Block for Cesarean Delivery: Injection Site Pain as a New Complication and Dexamethasone Reduced Incidence.

BackgroundAlthough ultrasound-guided transversus abdominis plane block (TAPB) is widely used in multimodal analgesia after cesarean delivery (CD), the complications of TAPB during analgesia after CD have rarely been reported.MethodsA total of 84 cases of CD were randomly assigned to either a ropivacaine group (R group) or ropivacaine + dexamethasone group (RD group) in this double-blind trial. The pain site and pain degree at rest and during activity at 2 h, 6 h, 10 h, 12 h, 14 h, 16 h, 20 h, and 24 h after maternal surgery were recorded. The consumption of opioids at 24h, postoperative nausea, vomiting, exhaustion, and other adverse reactions were recorded.ResultsA total of 80 patients were included in the analysis of results. A total of 19 patients developed ISP, 14 in the R group and 5 in the RD group. The incidence of ISP in the R and RD groups was 35% and 12.5%, respectively. The results described above showed that combining dexamethasone with ropivacaine reduced the incidence of ISP, and the difference was statistically significant (P<0.05). Two groups of women with positive ISP had higher values of opioid consumption than women with negative ISP, but the difference was not significant.ConclusionDexamethasone as an adjuvant for ropivacaine can effectively relieve the ISP of ultrasound-guided TAPB after CD, and can enhance the analgesic effect of ropivacaine.

The effects of silicone-based resilient denture liners on pain: A randomized controlled trial

PurposeThis randomized controlled trial aimed to study the effects of lining mandibular complete dentures with silicone-based resilient denture liners, especially with respect to sensation. MethodsThe trial included completely edentulous patients who were willing to fabricate new set of complete denture. A random permuted block method (block size: 4) was used to assign participants to one of the following groups: mandibular conventional denture (CD) group or mandibular denture with resilient denture liner (RD) group. The outcomes were evaluated using both, objective measures (current perception threshold (CPT) and pain threshold (PT)) for external stimuli measured using the Neurometer CPT® and subjective measures (physical pain and psychological discomfort measured using the Japanese version of Oral Health Impact Profile for Edentulous patients—OHIP-EDENT-J). The outcomes were measured twice, at immediately after completion of denture adjustments (first measurement), and 3 months after the completion of denture adjustments (second measurement). All outcomes were analyzed using the Student t-test. A p-value of <0.05 was considered statistically significant. ResultsCPT was significantly higher with RD than CD only at second measurement with frequency level of 2000 Hz and 5 Hz. The pain thresholds were significantly higher in the RD group than the CD group. The physical pain and psychological discomfort scores were significantly lower in the RD group than in the CD group. ConclusionThis study concludes that edentulous patients wearing mandibular complete dentures with silicone-based resilient denture liners dull perception mandibular ridge mucosa and felt less pain than those without the liners.

Dexmedetomidine combined with ropivacaine in ultrasound-guided tranversus abdominis plane block improves postoperative analgesia and recovery following laparoscopic colectomy.

The present prospective, double blind, randomized clinical study was designed to evaluate whether dexmedetomidine (Dex) combined with ropivacaine for tranversus abdominis plane (TAP) block could improve analgesic quality and duration, and promote recovery following laparoscopic colectomy. Following induction of anesthesia, ultrasound-guided bilateral TAP block was performed in 60 patients scheduled for elective laparoscopic colectomy with either 20 ml of 0.375% ropivacaine plus 2 ml normal saline 0.9% (R group), or 20 ml of 0.375% ropivacaine plus 2 ml Dex (0.5 µg/kg) (RD group). Visual analogue scale (VAS) score for pain, sedation level, length of hospital stay (LOS), and bowel function recovery time and associated complications were recorded. Overall patient satisfaction with postoperative pain management was also assessed. The hemodynamic variables were not significantly different between the two groups during the surgery. However, the duration of analgesia was significantly longer in the RD group compared with the R group (P<0.05). VAS scores at 1, 2, 6 and 12 h following surgery were significantly decreased in the RD group compared with those in the R group (P<0.05). There was no significant difference in sedation level between the two groups. Notably, postoperative nausea and vomiting in the RD group was significantly decreased compared with those in the R group in the first 24 h (P<0.05). There were no serious adverse events in any group. Furthermore, 90.0 and 66.7% patients were satisfied with the postoperative pain management in the RD group and R group, respectively. The postoperative first bowel movement time was significantly shorter in the RD group compared with the R group (P<0.05). However, the LOS was not significantly different between the two groups. In conlusion, the addition of Dex to ropivacaine could significantly improve the analgesic quality and duration of TAP block, which in turn promotes recovery following laparoscopic colectomy.

Novel Respiratory Impedance-Based Phenotypes Reflect Different Pathophysiologies in Chronic Obstructive Pulmonary Disease Patients.

PurposeThe forced oscillation technique (FOT) is a non-invasive method to measure respiratory impedance, the respiratory resistance (Rrs) and reactance (Xrs). The disease probability measure (DPM) is a useful computed tomography (CT) imaging variable for the assessment of gas trapping and emphysema in patients with chronic obstructive pulmonary disease (COPD) using pairs of inspiratory and expiratory CT images. We aimed to develop FOT-based phenotypes and determine whether the phenotypes and their imaging characteristics could facilitate the understanding of COPD pathophysiology.Patients and methodsFOT and spirometry were examined in 164 COPD patients and 22 non-COPD smokers. COPD patients were divided into four FOT-based phenotypes (NL, normal group; RD, resistance-dominant group; XD, reactance-dominant group; and MIX, mixed group) based on the 3rd quartile values of R5 (Rrs at 5Hz) and X5 (Xrs at 5Hz) in the non-COPD group. The emphysematous lesions and the airway lesions were quantitatively assessed in CT images by low attenuation volume and the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), respectively. DPM imaging analysis was also performed in 131 COPD patients. We investigated the differences in COPD parameters between the FOT-based phenotypes.Results√Aaw at Pi10 were significantly higher in the RD, XD, and MIX groups than in the NL group. The XD group showed lower pulmonary function and higher dyspnea scores than the RD group. No significant changes in DPM values were observed between the RD and the NL groups. The gas-trapping area was significantly higher in the XD group than in the NL group. The MIX group showed the highest dyspnea score, most emphysematous lesions, and the lowest forced expiratory volume in 1 s % predicted value.ConclusionThe FOT-based phenotyping may be useful to assess pathophysiological changes of COPD with CT assessments.

Impact of pathologic complete response on survival after neoadjuvant chemotherapy in early-stage breast cancer: a population-based analysis.

Achieving a pathologic complete response (pCR) has been associated with improved long-term outcomes in clinical trials. However, the benefit of achieving pCR across subtypes and its prognostic effect on real-world outcomes has not been well described. A retrospective analysis of the Breast Cancer Outcomes Unit database was undertaken to identify patients with stage I-III breast cancer treated with neoadjuvant chemotherapy from 2005 to 2010 in British Columbia. Patients were separated into two groups: those with pCR and those with residual invasive disease in the breast/axillary lymph nodes (RD). The primary endpoint was relapse-free survival (RFS). Key secondary endpoints included breast cancer-specific survival (BCSS) and overall survival (OS). Of 267 patients identified, 74 patients (28%) achieved pCR and 193 patients (72%) had RD. Median follow-up was 7.5years. The 5-year RFS was higher in the pCR group compared to the RD group (84% vs 70%; HR 0.45, p = 0.011). The 5-year BCSS was also higher in the pCR group than in the RD group (90% vs 77%; HR 0.39, p = 0.014). In multivariable analyses, pCR was associated with improved RFS (HR 0.39, p = 0.0077) and BCSS (HR 0.35, p = 0.015), whereas traditional pathological prognostic factors were not. Patients with TNBC who achieved pCR had improved RFS and BCSS compared to those with RD (HR 0.26, p = 0.020 and HR 0.35, p = 0.090, respectively). A similar but non-statistically significant trend was seen in the HER-2-positive and ER + subtypes. Achieving pCR after neoadjuvant chemotherapy was associated with clinically meaningful improvements in survival parameters in a real-world setting. The cumulative data support pCR as a valid surrogate endpoint in both clinical trials and population-based settings.

Overall Survival Benefit of Ixazomib, Lenalidomide and Dexamethasone (IRD) over Lenalidomide and Dexamethasone (RD) in RRMM Patients Treated in Routine Clinical Practice: Results from the Czech Registry of Monoclonal Gammopathies (RMG)

Background : Outcomes reported in real-world practice versus controlled clinical trials show markedly shorter treatment durations, progression free survival (PFS) and overall survival (OS). Understanding effectiveness of therapeutic regimens in routine practice is critical for treating physicians as well as for regulatory and reimbursement authorities. We have performed a real-world comparison of two regimens, ixazomib, lenalidomide and dexamethasone (IRD) triplet and lenalidomide and dexamethasone (Rd) doublet in patients with relapsed and/or refractory multiple myeloma (RRMM) treated in seven Czech and one Slovak hematology-oncology centers. Patients and methods: Between 3/2015 and 5/2017, 344 patients with RRMM were treated with either IRD (N=127) or RD (N=217). Patients selected for both cohorts had the same inclusion and exclusion criteria. Patient baseline characteristics were well balanced. The data were collected through the Czech Registry of Monoclonal Gammopathies (RMG), which is an international database gathering data from patients with monoclonal gammopathies within Central Europe. Results: The median follow-up in the IRD vs RD arm was 20.8 vs 15.5 months, respectively. Median PFS in pts with 1-3 prior lines for the IRD cohort was 23.1 months (95% CI 11.8-34.5 months) and 11.6 months (95% CI 8.4-11.8 months) for the RD cohort favoring the all-oral triplet (p=0.001). The median PFS for all patients including 4+ line of therapy was 17.5 months (95% CI 10.3-24.7) in the IRD cohort versus 11.5 months (95% CI 8.6-14.3) in the RD group (p=0.005). Median OS for pts with 1-3 prior lines for IRD cohort was not reached, and was 27.1 months (95% CI 23.1-31.1 months) in the RD cohort (p=0.002). Median OS for all patients, including 4+ lines of treatment was 36.6 months in the IRD vs 26.0 months in the RD cohort (p=0.008). The PFS benefit of IRD over RD was observed in most of the assessed subgroups; in younger pts ≤65 years with hazard ratio (HR) 0.58, in pts 66-75 years HR 0.64. There was a trend towards better PFS in patients with lower ISS stage; ISS1 HR 0.53, ISS2 HR 0.58 and ISS3 the HR was 0.87. Patients in the 1st relapse (HR 0.53) benefited most from the IRD, followed by the 2nd relapse (HR 0.58), 3rd relapse (HR 0.90) and pts relapsing after 4+ therapies (HR 0.88). The PFS benefit of IRD regimen was observed in pts regardless of previous stem cell transplantation; transplant-eligible patients HR 0.51 and transplant-ineligible HR 0.71. Patients who did not benefit from the triplet regimen were those over 75 years of age and pts with the presence of extramedullary disease. The IRD treatment was well tolerated. The safety profile was concordant with previously reported data. Conclusions: This RMG comparative cohort analysis shows PFS benefit of all-oral IRD regimen over RD in the real world setting, and confirms growing evidence that long term outcomes with IRD triplet are comparable with phase 3 TOURMALINE-MM1 trial. Our analysis also shows an overall survival benefit of IRD over RD treatment. Patients older than 75 years, with 4+ lines of therapy and presence of extramedullary disease did not profit from addition of ixazomib to RD doublet.Additional data with larger patient populations confirming RWE effectiveness are warranted. With support of AZV 17-29343A, NV18-03-00500, FNOl 00098892, IGA-LF-2019-001, PROGRES Q40/08, MH CZ-DRO (UHHK, 00179906) Disclosures Minarik: Celgene: Consultancy, Honoraria, Research Funding; Amgen, BMS, Janssen-Cilag, Takeda: Consultancy, Honoraria. Straub:Amgen, Takeda, Celgene: Consultancy. Spicka:Celgene: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy; Takeda: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Sanofi: Consultancy. Skacel:Millennium Pharmaceuticals, Inc., subsidiary of Takeda Pharmaceutical Company Limited: Employment. Maisnar:Janssen, Amgen, Celgene, Takeda, BMS: Consultancy, Honoraria.

PF638 VENOUS AND ARTERIAL THROMBOTIC EVENTS IN MYELOMA PATIENTS TREATED WITH IXAZOMIB, LENALIDOMIDE AND DEXAMETHASONE (IRD) OR LENALIDOMIDE AND DEXAMETHASONE (RD)

Background: Patients with multiple myeloma (MM) are at increased risk of venous thromboembolism (VTE). Immunomodulatory agents (IMiDs) are known to contribute to this increased VTE risk. Less is known about the risk of arterial thrombosis. Combining proteasome inhibitors (PI) or monoclonal antibodies to IMiDs improves clinical outcomes and is now a standard of care. Addition of the oral PI (Ixazomib) to Lenalidomide Dexamethasone (RD) significantly improves progression-free survival in patients with relapsed / refractory MM (RRMM), with no significant difference in VTE and arterial events with addition of Ixazomib to RD. Aims: To compare the incidence of VTE and arterial events in patients with RRMM treated with RD and IRD, with reference to previous VTE history, cardiovascular (CV) risk factors and use of thromboprophylaxis (TP). Methods: A retrospective review of patient records noting prior venous thrombosis and arterial risk factors in patients treated with RD or IRD. To avoid bias in patient selection, we reviewed RRMM patients treated with RD alone (July 2014 to February 2016) or after we routinely used Ixazomib with RD (IRD, February 2016 to July 2018). VTE and arterial events whilst receiving RD or IRD were noted. Results: Each group consisted of 88 patients (176 in total). Baseline patient characteristics were: median age 65 years in both groups (Range: 32–85 for IRD, 30–88 for RD); 54% male in both groups; median number of prior lines of therapy was 3 (range 1–5); median number cycles delivered 7 (range 1–32, IRD) and 7.5 (range 1–48, RD); 8 (9%) patients were still on treatment in the RD and 35 (40%) in IRD patients at the time of data collection. Prior VTEs were higher in the IRD group; 13 (15%) patients, compared to the RD group 8 (9%) patients. Potential arterial risk factors were higher in the RD group; 31 (35%) patients, compared to the IRD group, 20 (23%) patients. The commonest arterial risk factor was hypertension; 16 (52% of those with CV risk factors) on RD and 11 (55% of those with CV risk factors) on IRD patients. Four (5%) patients in each cohort had a prior CVA/TIA. Obesity (Body Mass Index ≥ 30) was higher in the RD group: 26 (30%) patients compared to the IRD group 18 (21%) patients. Aspirin VTE TP was given in 60 (62%) and 68 (77%) IRD and RD patients respectively. More DOAC prescriptions were noted in the IRD group (12 patients, 13%), vs RD (2 patients, 2%). In those patients receiving IRD; 5 (5.7%) VTEs (3 PE, 1 venous sinus thrombosis, 1 DVT). Four VTEs occurred on aspirin, the other on rivaroxaban TP. For RD there were 3 (3.4%) VTEs (1 PE and 2 DVT), all on aspirin TP. Two patients (2.3%) had arterial events whilst receiving IRD (TIA after 6 months with no risk factors; stroke after 3 months, hypertension only risk factor), 1 RD patient (1.1%) developed a stroke 11 months after starting RD (known hypertensive and diabetic). Summary/Conclusion: VTEs occur at a lower rate than reported; between 3 and 6%, compared to 8–11% in the Touramaline MM1 trial, however we note VTEs of potential clinical concern (PE or venous sinus thrombosis), 4 events in the IRD and 1 in the RD group. VTEs still occurred despite thromboprophylaxis. The IRD group had more previous VTEs, but a lower obesity rate. This requires further exploration. Arterial events occur at a similar rate to that reported (1–2%), and occur early in treatment, despite aspirin TP and in the absence of other risk factors. Strategies to prevent this are urgently needed.

PO-01-049 Testosterone counteracts metabolic syndrome-related changes in skeletal muscle fiber metabolism and improves exercise performance in the rabbit

Lifestyle modifications, including physical exercise (PhyEx) are well-known treatments for metabolic syndrome (MetS), a cluster of metabolic and cardiovascular risk factors often associated to hypogonadism. Given the trophic role of testosterone (T) on skeletal muscle (SkM) mass, this study was aimed at evaluating the effects of T treatment on SkM metabolism and exercise performance in male rabbits with high fat diet (HFD)-induced MetS. HFD rabbits, treated or not with T (HFD+T; 30 mg/kg/week) for 12 weeks were compared to regular diet animals (RD). A subset of each group were exercise-trained on a treadmill for 12 weeks. SkM samples were collected for subsequent analyses. HFD determined an increased gene expression of type-II (fast, glycolytic) and a significant decrease of type-I (slow, oxidative) muscle fiber markers, as compared to RD group. T reverted these effects, also inducing the expression of mitochondrial respiration chain enzymes and normalizing HFD-induced mitochondrial cristae reduction. Fiber typing by PAS-staining in SkM cross-sections confirmed a shift from type-I to type-II fibers in HFD, which was normalized by T. Moreover, T significantly increased the expression of both myogenic and muscle metabolism (insulin-dependent signaling, lipid turnover) markers. Preliminary Results in rabbit SkM satellite cells confirmed the positive effect of T on myogenesis. At the end of the PhyEx protocol, when compared to RD, HFD rabbits showed a significant reduction of both running distance and running time, while T counteracted this effect, also decreasing the lactate production. Muscle histology evidenced a further reduction of type-I fibers in HFD compared to RD and the positive effect of T in maintaining oxidative metabolism, as also demonstrated by mitochondrial ultrastructure analysis.

Association between coronary dominance and acute inferior myocardial infarction: a matched, case-control study

BackgroundPrevious studies have found a connection between left coronary artery dominance and worse prognoses in patient with acute coronary syndrome, which remains a predominant cause of morbidity and mortality globally. The aim of this study was to investigate whether coronary dominance is associated with the incidence of acute inferior myocardial infarction (MI).MethodsBetween January 2011 and November 2014, 265 patients with acute inferior MI and 530 age-matched and sex-matched controls were recruited for a case-control study in the Second Affiliated Hospital of Xi’an Jiaotong University in Xi’an, China. All participants underwent coronary angiography. The exclusion criteria included history of coronary artery bypass graft surgery, chronic or systemic diseases (including hepatic failure, kidney failure, hypothyroidism and Grave’s disease), ventricular fibrillation, and known allergy to iodinated contrast agent. Patients with left- or co-dominant anatomies were placed into the LD group and those with right-dominant anatomy were included in the RD group. The association of acute inferior MI and coronary dominant anatomy were assessed using multivariable conditional logistic regression, and to estimate the odds ratio (OR) and 95% confidence interval (95%CI).ResultsDistributions of right dominance were significantly different between the acute inferior MI group and control group (94.0% vs. 87.9%, P = 0.018). Univariable conditional logistic regression revealed that right dominance may be a risk factor for the incident acute inferior MI (OR: 2.137; 95% CI: 1.210–3.776; P = 0.009). After adjusting for baseline systolic blood pressure, heart rate, smoking status, diabetes mellitus, hypertension, hyperlipidaemia, and family history of coronary artery disease, results of multivariate conditional logistic regression showed that right dominance was associated with the incidence of acute inferior MI (OR: 2.396; 95% CI: 1.328–4.321; P = 0.004).ConclusionsRight coronary dominance may play a disadvantageous role in the incidence of acute inferior MI. However, further studies are needed to verify our findings, especially with regard to the underlying mechanisms.

Evaluation of Tacrolimus Levels and Risk of Acute Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant

Background Achieving therapeutic tacrolimus blood concentrations is crucial for decreasing the risk of developing acute graft-versus-host-disease (aGvHD) in allogeneic hematopoietic stem cell transplant (aHSCT) patients. Studies have suggested that tacrolimus levels in the first 1-2 weeks may affect the risk of aGVHD but therapeutic goals are not well established. This study explores tacrolimus levels and risk of GVHD during that time frame. Methods This study is a retrospective cohort single center chart review performed with 348 consecutive adult patients who received an aHSCT and were followed for at least 100 days post-transplant for aGvHD development. Patients that received a transplant from a cord blood or participated in aGvHD prophylaxis clinical trials were excluded. The primary endpoint was aGvHD grades II - IV incidence. Serum tacrolimus levels were evaluated from days -1 to +100 post-transplant. Serum tacrolimus levels were divided into time intervals of days 0 - 7 and days 0 - 14 post-transplant. Receiver operator characteristic curves (ROC) were used to quantify serum tacrolimus levels as predictors of aGvHD grades II-IV. Using the ROC analysis and Youden's Index, optimal cutpoints in the tacrolimus level distribution for the individual time intervals were assessed. From this, patients were analyzed based on whether they achieved mean tacrolimus serum levels below the cutpoint (low group) or if they achieved a mean tacrolimus level above the cutpoint (high group). Results Within the URD group during days 0-7 post-transplant, the low group and high group demonstrated a mean tacrolimus level of 11.3 and 14.5 respectively, with significantly less aGVHD observed in the high group (38% vs 57.2%, p = 0.021). In respect to days 0-14, the low group and high group demonstrated a mean tacrolimus level of 10.4 and 13 respectively, again with significantly less aGVHD in the high group (35.6% vs 57.3%, p = 0.012). Within the RD group during days 0-7 post-transplant, the low group and high group demonstrated a mean tacrolimus level of 10.9 and 13.7 respectively, also with significantly less aGVHD in the high group (21.7% vs 38.7%, p = 0.042). In respect to days 0-14, the low and high group demonstrated a mean tacrolimus level of 10.2 and 13.1 respectively. However, there was not a significant difference in aGVHD (25.7% vs 35.9%, p = 0.272). Conclusion Higher levels of tacrolimus in the first 2 weeks after allogeneic stem cell transplant appear to correlate with a lower incidence of grade II-IV aGVHD. Higher levels in both weeks 1 and 2 were associated with a 37% reduction in the URD group while higher levels in week 1 were associated with a 44% in the RD group. While larger studies would help to clarify more specific ranges, this data suggests that target tacrolimus levels should be 14-15 ng/ml in the first 2 weeks post allogeneic transplant to decrease rates of grade II-IV aGVHD.

Training endogenous pain modulation: a preliminary investigation of neural adaptation following repeated exposure to clinically-relevant pain.

Analgesic treatments that aim to eliminate pain display marginal success in relieving chronic pain and may increase pain vulnerability. Repeated exposure to pain may result in increased pain modulation via engagement of anti-nociceptive brain regions. It was hypothesized that repeated exposure to delayed onset muscle soreness (DOMS) would result in increased pain modulatory capacity (PMC) via functional neural adaptation. 23 healthy participants completed Baseline and Follow Up resting-state fMRI and quantitative sensory testing (QST) visits 40days apart. Participants were randomized to two groups: A Repeated DOMS Group (RD Group) that received four, weekly DOMS inductions and a Control Group that received one baseline induction. Daily pain ratings were collected for seven days post-induction, as were quantitative sensory testing (QST) metrics at baseline and Follow Up. Regional functional connectivity (FC) was estimated among areas involved inpain modulation. Seed and network FC was estimated among areas involved in pain modulation and sensory processing. Changes in FC were compared between groups. The RD Group displayed significant reductions in post-DOMS pain ratings and significant changes in thermal QST measures. RD Group participants displayed greater adaptation in nucleus accumbens-medial prefrontal cortex (NAc-mPFC) FC and insensorimotor network (SMN) connectivity with the dorsomedial, ventromedial, and rostromedial prefrontal cortices. Changes in SMN-PFC connectivity correlated with reductions in post-DOMS affective distress. Results suggest that repeated exposure to clinically-relevant pain results in adaptations among brain regions involved in pain modulation. Repeated exposure to clinically-relevant pain may serve as a mechanism to increase PMC via inhibition of emotional valuation of painful stimuli.

Retrobulbar dexmedetomidine in pediatric vitreoretinal surgery eliminates the need for intraoperative fentanyl and postoperative analgesia: A randomized controlled study

Purpose:This study evaluated the efficacy of retrobulbar ropivacaine plus dexmedetomidine compared with systemic fentanyl in pediatric vitreoretinal (VR) surgery.Methods:This prospective double-blind, randomized controlled study was performed in 60 children undergoing VR surgery, age from 2 to 7 years. After general anesthesia, the following procedure was administrated: (1) retrobulbar block with 0.5% ropivacaine plus dexmedetomidine 1 μg/kg (group RD, n = 20), (2) retrobulbar block with 0.5% ropivacaine (group RB, n = 20), and (3) control group with general anesthesia only (group F, n = 20). Hemodynamics, postoperative pain scores, anesthetics consumption (remifentanil, propofol, fentanyl), and emergence agitation were recorded.Results:Respiratory depression was observed in 7 of the 20 patients in group F after the laryngeal mask airway was removed in the operating room, compared with none in groups RD and RB. All patients in group F required intraoperative rescue fentanyl (average intraoperative fentanyl consumption, 26.6 ± 12.6 μg per patient). Some rescue fentanyl was required in group RB (three patients required one dose of rescue fentanyl). Patients in group RD required none. Groups RD and RB reported lower pain scores than group F at 4 h postoperatively (RD group: P < 0.001; RB group: P =0.002); pain scores in group RD were lower than that in group F at 6 h postoperatively (P < 0.001).Conclusion:Retrobulbar dexmedetomidine as an adjuvant to ropivacaine is a safe and effective alternative to systemic fentanyl. This regimen provides better pain management, hemodynamic stability, and stress response suppression in pediatric VR surgery.

Intraperitoneal Ropivacaine with Dexmedetomidine or Fentanyl for Postoperative Analgesia Following Laparoscopic Cholecystectomy: A Comparative Randomized Trial.

Background:Intraperitoneal local anesthetic is an effective analgesic approach following laparoscopic cholecystectomy.Aims:The aim of the present study was to compare the antinociceptive effects of intraperitoneal ropivacaine plus fentanyl with ropivacaine plus dexmedetomidine in patients undergoing laparoscopic cholecystectomy.Settings and Designs:This was randomized, prospective, double-blinded, observational clinical study.Methods:A total of 80 patients, undergoing elective laparoscopic cholecystectomy under general anesthesia were randomly assigned to one of the two equal groups to receive either of the following: Group RF (n = 40) were given 30 mL of 0.2% ropivacaine combined with 1 μg/kg fentanyl (diluted in 2 mL normal saline) and Group RD (n = 40) were given 30 mL of 0.2% ropivacaine combined with 1 μg/kg dexmedetomidine (diluted in 2 mL normal saline) through trocars. The quality of analgesia was assessed using visual analog scale score (VAS). Time to the first request of analgesia, the total dose of analgesic in the first 24 h and adverse effects were noted.Statistical Analysis:The data were analyzed with the Students’ t-test and Chi-square test.Results:VAS score at different time intervals, overall VAS in 24 h was significantly lower (1.68 ± 0.46 vs. 4.47 ± 0.94), time to first request of analgesia (min) was longest (122.7 ± 24.5 vs. 89.3 ± 13.2) and total analgesic consumption (mg) was lowest (95.3 ± 15.6 vs. 135.7 ± 75.1) in RD group than in RF group.Conclusion:The antinociceptive effect of the intraperitoneal instillation of ropivacaine in combination with dexmedetomidine is superior to ropivacaine combined with fentanyl.

Effects of electroacupuncture at different time during reperfusion on the expression of Bcl-2 and Beclin1 in myocardial tissue in rats with myocardial ischemia reperfusion injury

To compare the effects of electroacupuncture (EA) at different time during reperfusion on the expression of autophagy-related protein Bcl-2 and Beclin1 in myocardial tissue in rats with myocardial ischemia reperfusion injury (MIRI), and to explore the autophagy-related mechanism of EA on protecting MIRI. A total of 72 SD rats were randomly divided into a sham operation group, a model group, a RA group, a RB group, a RC group and a RD group, 12 rats in each group. Except the sham operation group, the rats in the remaining groups were treated with ligating the left anterior descending artery (LAD) for 30 minutes followed by reperfusion to establish the model of MIRI. The rats in the sham operation group were treated with crossing a line through the LAD. The rats in the model group did not receive treatment. The rats in the RA group, RB group, RC group and RD group were treated with EA at "Neiguan" (PC 6) for 20 min, starting at 0 h, 0.5 h, 1 h, 2 h after reperfusion. Evans Blue-TTC double-staining was employed to evaluate myocardial infarct size; the serum CK-MB was detected by ELISA and the expression of Bcl-2 and Beclin1 protein in myocardial tissue were detected by Western blot. Compared with the model group, the percentage of myocardial infarct size in the RB group, RC group and RD group was decreased significantly (all P<0.05), and the reduction in the RB group was more significant than that in the RC group and RD group (both P<0.05). Compared with the sham operation group, the expression of CK-MB and Beclin1 in the model group was significantly increased, but the expression of Bcl-2 was significantly decreased (all P<0.01). Compared with the model group, the expression of CK-MB and Beclin1 was decreased significantly in RA group, RB group, RC group and RD group (all P<0.05), but the expression of Bcl-2 was significantly increased (all P<0.05). Compared with the RA group, the expression of CK-MB was decreased in the RB group and RC group (both P<0.05) but the expression of Bcl-2 was increased (both P<0.01); the expression was not significantly different from that in the RD group (P>0.05); the increasing of Bcl-2 in the RB group was more significant than that in RC group (P<0.05). The expression of Beclin 1 in the RB group was significantly lower than that in the RA group (P<0.05), but there was no significant difference among other EA groups (all P>0.05). EA at different time during reperfusion could reduce myocardial infarct size in rats with MIRI, and EA at 0.5 h after reperfusion has best efficacy; this protective effect may be achieved by increasing Bcl-2 expression and reducing Beclin1 expression to inhibit overautophagy during reperfusion.

A Comparative Study Between Two Different Doses of Dexmedetomidine Combined with Ropivacaine in Ultrasound Guided Supraclavicular Brachial Plexus Block

Background: Though, various studies have been conducted to show the efficacy of dexmedetomidine as an adjuvant to brachial plexus block, there is no clear consensus for its optimal dose. We compared 2 different doses of dexmedetomidine (1mcg/kg Vs 2mcg/kg) with ropivaciane in USG guided brachial plexus block for the quality of anesthesia and analgesia. Materials and Methods: Fifty patients (18-50years, 50-60kgs), ASA PS I and II undergoing surgery of upper limb were enrolled in this prospective, double blind, randomized control trial. Group Rd received 19ml of 0.5% Ropivaciane with 1mcg/kg of dexmedetomidine (total 20ml), and Group RD received 19ml of 0.5% Ropivacaine with 2mcg/kg of dexmedetomidine (total 20ml). Onset and duration of sensory and motor block, duration of analgesia, sedation score, hemodyanamic changes were compared. We also monitored for various un towards effects. Results: The onset time of sensory and motor block (9.36±1.114 mins and 14.40 ± 1.528 mins in group Rd vs 8.32 ±0.945 mins and 12.40 ± 1.21 mins in group RD) were not significantly different between two groups (p-value &gt; 0.05).The duration of sensory and motor block (596.20 ± 76.859 mins and 541.20±81.564 mins in group Rd vs 730.80 + 65.187 mins and 659.80±93.607 mins in group RD) were not significantly longer in group RD than group Rd (p-value &gt; 0.05). The duration of analgesia (626.00±70.475 mins in group Rd vs 754.00±60.139 mins in group RD) were not significantly longer in group RD than group Rd (p-value &gt; 0.05). Hemodynamic parameters were also comparable between two groups (p-value &gt;0.05) but 3 patients in RD group (2mcg/kg) developed bradycardia and required treatment with atropine whereas in Rd group (1mcg/kg) none developed bradycardia. Conclusions: There is no significant difference in the onset and duration of block between the two groups. However, higher dose of dexmedetomidine is associated bradycardia. Hence, in comparision with 2mcg/kg, 1mcg/kg of dexmedetomidine is better adjuvant to 0.5% ropivaciane in terms of safety and effectiveness.Keywords: dexmedetomidine; ropivacaine; supraclavicular brachial plexus block.

Efficacy of perineural dexamethasone with ropivacaine in thoracic paravertebral block for postoperative analgesia in elective thoracotomy: a randomized, double-blind, placebo-controlled trial.

PurposeThe purpose of this study was to assess the efficacy of perineural dexamethasone with ropivacaine in multimodal analgesia for thoracic paravertebral block (TPVB) in patients undergoing elective thoracotomy.Patients and methodsNinety-six patients undergoing thoracotomy were enrolled in this trial and randomized to adjuvant therapy for TPVB: group S (saline), group R (0.5% ropivacaine), or group RD (5 mg dexamethasone and 0.5% ropivacaine). Postoperative analgesia, recovery duration, and chronic pain were recorded.ResultsGroups R and RD spent less time in the postanaesthesia care unit, had earlier out-of-bed activity, and had shorter postoperative hospital stays compared with group S. The RD group regained consciousness faster and had lower acute pain scores and used less patient-controlled analgesia during the first 72 h after surgery compared with group S. Postthoracotomy pain was decreased in group RD (19.0%) compared with group S (47.6%) 3 months postoperatively, p = 0.050.ConclusionPerineural dexamethasone with ropivacaine for TPVB improves postoperative analgesia quality, reduces recovery time, and may decrease the incidence of chronic pain after thoracotomy with an opioid-based anesthetic regimen.

Impact of an institutional change from routine to highly selective diversion of a low anastomosis after TME for rectal cancer

IntroductionThe need for routine diverting ileostomy following restorative total mesorectal excision (TME) is increasingly debated as the benefits might not outweigh the disadvantages. This study evaluated an institutional shift from routine (RD) to highly selective diversion (HSD) after TME surgery for rectal cancer. Materials and methodsPatients having TME with primary anastomosis and HSD for low or mid rectal cancer between December 2014 and March 2017 were compared with a historical control group with RD in the preceding period since January 2011. HSD was introduced in conjunction with uptake of transanal TME. ResultsIn the RD group, 45/50 patients (90%) had a primary diverting stoma, and 3/40 patients (8%) in the HSD group. Anastomotic leakage occurred in 10 (20%) and three (8%) cases after a median follow-up of 36 and 19 months after RD and HSD, respectively. There was no postoperative mortality. An unintentional stoma beyond 1 year postoperative was present in six and two patients, respectively. One-year stoma-related readmission and reoperation rate (including reversal) after RD were 84% and 86%, respectively. Corresponding percentages were significantly lower after HSD (17% and 17%; P < 0.001). Total hospital stay within one year was median 11 days (IQR 8–19) versus 5 days (IQR 4–11), respectively (P < 0.001). ConclusionThis single institutional comparative cohort study shows that highly selective defunctioning of a low anastomosis in rectal cancer patients did not adversely affect incidence or consequences of anastomotic leakage with a substantial decrease in 1-year readmission and reintervention rate, leading to an overall significantly reduced hospital stay.