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Thoracic epidural analgesia is known to have superior perioperative pain control over intravenous opioid analgesia in open abdominal surgery and is an essential enhanced recovery after surgery component in major abdominal surgeries. Recently, the ultrasound-guided thoracic epidural catheter placement (TECP) technique has drawn attention as an alternative for the traditional landmark palpation-based TECP or fluoroscopic-guided TECP technique due to the equipment’s improvement and increased popularity. However, only a small number of studies have introduced the advantages and usefulness of ultrasound-guided TECP. Moreover, a certain level of ultrasound-guided in-plane technique is required to perform this technique. Thus, to apply ultrasound-guided TECP correctly and reduce the likelihood of side effects and complications, the practitioner must have a thorough understanding of the anatomical region, optimal block positioning, device selection, and management. In this technical review, the authors have compared the advantages and disadvantages of ultrasound-guided TECP to traditional techniques and described its technical aspects from patient positioning, ultrasound probe selection and scanning, needle insertion under ultrasound guidance, and successful thoracic epidural catheter insertion confirmation through ultrasound imaging. Additionally, the recommended epidural catheter tip placement level with the extent of its injectate epidural spread is further described in this review in reference to a recent prospective study published by the authors.

BACKGROUND AND OBJECTIVES Patients who undergo total knee arthroplasty (TKA) have a risk of postoperative anaemia. This observational study evaluated whether single-dose intravenous ferric carboxymaltose (FCM) administered immediately after TKA facilitates the correction of anaemia. MATERIALS AND METHODS We retrospectively analysed 722 patients who underwent primary TKA. The FCM group receiving 1000 mg intravenous FCM within one postoperative hour was compared with the non-FCM group that did not receive the medication. A propensity score matching with multiple logistic regression analysis was used to minimize intergroup differences in the baseline characteristics and postoperative blood loss. The rate and severity of postoperative anaemia were compared between the groups, along with haemoglobin (Hb) value, transfusion rate and complications. RESULTS After propensity score matching, 231 patients were included in each group. In the FCM group, the rate of anaemia at postoperative day (POD) 7 (p = 0.021) and postoperative week (POW) 5 (p

While the use of fluoroscopy-guided transforaminal epidural steroid injection (TFESI) to help spread the injectate toward the ventral side has increased, this procedure has a radiation risk. Recently, ultrasound has been widely used in the medical field; among ultrasound methods, color Doppler is useful for predicting the direction of the injectate.This study describes a novel technique employing color Doppler to help predict epidural space spread in interlaminar epidural steroid injection (ILESI).Prospective observational study.The study took place at a single pain clinic within a medical center in Jeonju, Republic of Korea.We enrolled 35 patients scheduled for lumbar epidural steroid injection (ESI). Ultrasound-guided epidural lateral parasagittal interlaminar injection was performed and real-time images using color Doppler were recorded during injections of 5 mL of 0.1% ropivacaine containing contrast dye with dexamethasone 5 mg (1 mL). Fluoroscopy-guided TFESI was performed if it was difficult to perform the procedure based on ultrasound images.The analysis included 30 images from 30 patients. The observed sensitivity, specificity, positive predictive value, and negative predictive values of the ultrasound color Doppler were 100%, 89.5%, 84.6%, and 100%, respectively. The agreement with ultrasound color Doppler was 93.3%.The sample size was relatively small.The main advantage of ultrasound-guided ILESI is the lack of radiation exposure and contrast medium requirement. Color Doppler may be a reliable imaging modality to predict epidural space spread during ultrasound-guided ILESI. It is worth predicting the spread in the anterior epidural space (AES) by first attempting ultrasound-guided ESI. If the injectate has not spread to the AES, fluoroscopy-guided TFESI may be a good option after confirming improvement of the patient's symptoms.

Staggered bilateral total knee arthroplasty, two procedures performed 4-7 days apart during a single hospitalization, has an increased risk of blood transfusion. This observational study aimed to evaluate whether immediate post-operative single, high-dose intravenous iron supplementation could reduce transfusion requirements and facilitate anaemia recovery in patients.We retrospectively analysed 131 patients who underwent staggered bilateral total knee arthroplasty. The ferric carboxymaltose (FCM) group received 1000 mg of FCM after the first operation. The non-FCM group did not receive intravenous iron. The transfusion rate and post-operative complications were compared between the groups. The anaemia rate was evaluated pre-operatively, during hospitalization, and 5 weeks after the second total knee arthroplasty.The FCM group comprised 78 patients (59.5%). The rate (21.8% vs. 47.2%, p = 0.004) and amount of transfusion (0 [0-2] vs. 0 [0-0], p = 0.001) was significantly lower in the FCM group than in the non-FCM group. Although both groups' pre-operative haemoglobin concentrations were not significantly different, the FCM group demonstrated higher haemoglobin values 5 weeks post surgery (12.25 ± 0.83 mg/dl vs. 11.48 ± 1.36 mg/dl, p 0.001). More non-FCM patients developed moderate to severe anaemia at 5 weeks post surgery (p 0.001). The mortality and complication rates were not significantly different.Immediate post-operative, high-dose, intravenous iron treatment may contribute to reduced transfusion rates, facilitate haemoglobin recovery after staggered bilateral total knee arthroplasty, and minimize the development of moderate to severe anaemia.

Background and Objectives: Although epidural steroid injections are used as an effective treatment, this technique is associated with rare but serious ischemic complications, especially when particulate steroids are used. However, recent studies have reported that even if non-particulate steroids are used, particulates are formed by the interaction with some local anesthetics (LA), causing ischemic complications. This observational study evaluated commonly used combinations of non-particulate steroids and LA with contrast media via microscopic analysis and analyzed the chemical properties of each mixture to identify the correlation of particulate formation. Materials and Methods: Commonly used clinical non-particulate and particulate steroids, contrast media, and LA agent combinations were evaluated macroscopically and microscopically. The pH values were also measured at both room temperature (26 °C) and body temperature (36 °C). Where particulates were observed, the particulate size was measured. Results: Macroscopically, the mixture of non-particulate steroid and ropivacaine had a slightly cloudy appearance at all concentrations, but there was no visible particulate. However, when observed under a microscope, the pH-dependent particulate formation was observed at all concentration combinations tested. (0.1% ropivacaine: from 19 μm to 70 μm, and 0.2% ropivacaine: from 37 μm to 108 μm at room temperature (26 °C)). When contrast media was mixed or the temperature was raised to body temperature (36 °C), the number and size of the particulates decreased or dissolved. Conclusions: The combination of ropivacaine and dexamethasone, a non-particulate steroid, mainly used in epidural injections, forms particulates. However, when mixed with contrast media, particulates are dissolved because of changes in pH and factors affecting particulate formation. In fluoroscopy-guided injections, the use of contrast media could resolve particulate formation.

The psoas-to-lumbar index (PLVI) has been reported as a simple and easy way to measure central sarcopenia. However, only few studies have evaluated the association between PLVI and survival in surgical patients. This study evaluated the association between preoperative PLVI and mortality in elderly patients who underwent hip fracture surgery. We retrospectively analyzed 615 patients who underwent hip fracture surgery between January 2014 and December 2018. The median value of each PLVI was calculated according to sex, and the patients were categorized into two groups on the basis of the median value (low PLVI group vs. high PLVI group). Cox regression analysis was performed to evaluate the risk factors for 1 year and overall mortalities. The median values of PLVI were 0.62 and 0.50 in men and women, respectively. In the Cox regression analysis, low PLVI was significantly associated with higher 1 year (hazard ratio (HR): 1.87, 95% confidence interval (CI): 1.18–2.96, p = 0.008) and overall mortalities (HR: 1.51, 95% CI: 1.12–2.03, p = 0.006). Low PLVI was significantly associated with a higher mortality. Therefore, PLVI might be an independent predictor of mortality in elderly patients undergoing hip fracture surgery.

At centers with pressure on rapid operating room turnover, onset time is one of the important considerations for choosing a local anesthetic drug. To hasten the onset of the block, higher concentrations of local anesthetics are sometimes used. However, the use of diluted local anesthetics may be safer. Therefore, we aimed to compare the onset times of equipotential levobupivacaine and ropivacaine at low concentrations for infraclavicular brachial plexus block. Adult patients undergoing upper extremity surgery under ultrasound-guided infraclavicular brachial plexus block at our center were randomly allocated to the levobupivacaine and ropivacaine groups. Infraclavicular brachial plexus block was induced with 0.25% levobupivacaine or 0.375% ropivacaine depending on the assigned group. The degrees of sensory and motor blockade were assessed for 40 min after the administration of local anesthetics. A total of 46 patients were included in the analysis. Infraclavicular brachial plexus block with 0.25% levobupivacaine and 0.375% ropivacaine provided sufficient surgical anesthesia. The sensory onset time of 0.375% ropivacaine was shorter than that of 0.25% levobupivacaine (group R, 15 [15.0–22.5] min; group L, 30 [17.5–35.0] min, p = 0.001). There were no significant differences in other block characteristics and clinical outcomes between the two groups. Thus, when a quicker block onset is required, 0.375% ropivacaine is a better choice than 0.25% levobupivacaine.Trial registration ClinicalTrials.gov (NCT03679897).

A continuous interscalene brachial plexus block (CIBPB) is usually administered before surgery in awake patients. However, the use of CIBPB before surgery could hinder the identification of nerve injuries after total shoulder arthroplasty (TSA). This study aimed to compare the analgesic effects of preoperatively and postoperatively initiated CIBPBs in patients undergoing TSA. The medical records of patients who underwent TSA between January 2016 and August 2020 were retrospectively reviewed. The following analgesic phases were used: intravenous (IV) patient-controlled analgesia (PCA) phase (IV PCA group, n = 40), preoperative block phase (PreBlock group, n = 44), and postoperative block phase (PostBlock group, n = 33). The postoperative initiation of CIBPB after a neurologic exam provided better analgesia than IV PCA and had no differences with the preoperative initiation of CIBPB, except for the worst pain at the postanesthetic care unit. Opioid consumption was significantly greater in the IV PCA group, but there were no differences between the PreBlock and PostBlock groups on operation day after the transfer to the general ward. The initiation of CIBPB after a patient’s emergence from general anesthesia had comparable analgesic efficacy with preoperative CIBPB but offered the chance of a postoperative neurologic exam.

To compare the clinical efficacy and safety of arthroscopy-guided continuous suprascapular nerve block and ultrasound-guided continuous interscalene block in postoperative analgesia in patients undergoing arthroscopic rotator cuff repair.A prospective study was performed between March and November 2020. In total, 76 patients were enrolled and divided into 2 groups: in the 38 patients of group 1 (arthroscopy-guided continuous suprascapular nerve block), an indwelling catheter was introduced via the Neviaser portal under arthroscopic view before closing the portal at the end of the surgery; and in the 38 patients of group 2 (ultrasound-guided continuous interscalene block), an indwelling catheter was inserted and directed toward the interscalene brachial plexus prior to the surgery under ultrasound guidance. The primary outcome was the pain score measured by the visual analog scale at postoperative 24 hours during admission. Comparisons were conducted at different time points (postoperative 4, 8, 24, and 48 hours). The secondary outcome was any of these events: neurologic complications, such as sensory/motor change in the upper extremities; hemidiaphragmatic paresis; dyspnea; dysphonia; and Horner's syndrome. Opioid usage until postoperative 3 weeks was compared between the groups.The visual analog scale scores in groups 1 and 2 were comparable at each postoperative time point (analysis of variance, P = .919; trends, P = .132). Neurologic deficits were more common in group 2 than in group 1 (8 vs 32 patients, P.001). Decreased excursion of the diaphragm was more common in group 2 (partial or complete paresis of the hemidiaphragm: 1 vs 29 patients, P .001). Opioid consumption was similar in both groups (morphine milligram equivalents per kilogram; 1.75 vs 1.55, P = .195).Our findings show that arthroscopy-guided continuous suprascapular nerve block is not inferior to ultrasound-guided continuous interscalene block for postoperative pain control after arthroscopic rotator cuff repair while showing fewer temporary neurologic complications.Level II, prospective cohort study, interventional study.

BACKGROUND The strategy for bilateral total knee arthroplasty (TKA) depends on the timing of surgery for each knee. The purpose of this study was to determine whether the type of surgical strategy for bilateral TKA (staggered, staged, or simultaneous) influences the incidence of acute kidney injury (AKI) and related complications. METHODS Enrolled patients from a single tertiary teaching hospital were divided into 3 groups according to the surgical strategy for bilateral TKA: staggered (≤7 days between the first and second procedure; n = 368), staged (8 days to 1 year between the first and second procedure; n = 265), or simultaneous (n = 820). The incidence of AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria was assessed. The rates of major postoperative complications, major adverse cardiovascular and cerebral events, intensive care unit (ICU) admissions, and mortality were also evaluated. To reduce the influence of possible confounding factors, inverse probability of treatment weighting based on propensity-score analysis was used. RESULTS The primary outcome was the incidence of AKI according to surgical strategy. The staggered group had a lower rate of AKI compared with the other 2 groups (p < 0.001): 2.4% (9 of 368 patients), 6.0% (16 of 265), and 11.2% (92 of 820) in the staggered, staged, and simultaneous groups, respectively. CONCLUSIONS The type of bilateral TKA strategy was an independent risk factor for the development of AKI. The assessment of additional risk factors for the development of AKI is essential before deciding on surgical strategy. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Additional file 3: Table S2. The sample information used for the present analysis.

Additional file 7: Figure S4. PCA plot of the preAC-DEGs. The L-preAC (turquoise) and O-preAC (red) samples are dotted along the axis of the first two principal components (PC1 and PC2).

Additional file 11: Table S6. Statistical summary of the clinical information.

Additional file 5: Figure S2. GSEA analysis of LO-DEGs. Four selected gene sets from the GSEA analysis are presented here. (A) and (B) are the gene sets for inflammatory response and angiogenesis, respectively, showing significant enrichment in Le, and (C) and (D) are the gene sets for cellular respiration and cellular metabolism, respectively, showing significant enrichment in Oe. The left panels represent the graph of the enrichment score (ES) generated from the GSEA analysis, and the right panels are the heatmaps constructed by the gene sets with significant ES scores. The cyan and red bars on top of the heatmaps represent the ‘Le-AC’ and ‘Oe-AC’ samples, respectively.

Additional file 2: Table S1. Statistical thresholds tested for selecting DEGs.

Additional file 12: Figure S6. Schematic of the purification of AC and preAC cells from AT. Refer to the Materials and methods section for the detailed procedures depicted in this schematic.

Additional file 4: Table S3. Statistical thresholds used for testing to select three subcategories of AC-DEGs.

Additional file 8: Figure S5. Analysis of the functions of genes that are significantly altered between lean and obese adipogenesis. A. ‘Clusterprofile’ analysis of GO functional terms. Lean_Ag-DEGs and Obese_Ag-DEGs are intersected, leading to three subcategories: ‘LS’, ‘OS’, and ‘CA’ (see the main text). For LS, OS, and CA, DEGs are subdivided into upregulated (i.e., genes that are expressed at higher levels in ACs than in preACs) and downregulated genes (i.e., genes that are expressed at lower levels in ACs than in preACs). Upregulation and downregulation are further divided into four groups by considering the log2FC in gene expression along with the Q < 0.01 threshold. Functional enrichment of genes in each class is investigated and plotted by ‘Clusterprofiler’. Refer to the main text for the meaning of each colored box. B. Left: Box plot of expression levels of inflammatory genes in the ‘CA’ category. A total of 99 inflammatory genes were found by mapping these genes to the annotations on GeneCards (http://genecards.org). Box plots are constructed using the Log2FC values calculated for each of the 99 genes between the AC and preAC samples for the lean and obese conditions, respectively. Right: Square Venn diagram showing the numbers of pro-/anti-inflammatory genes. Statistical significance is estimated by Wilcoxon’s test.

Additional file 6: Figure S3. Schematic of the strategy for dividing the DEGs into eight subcategories‘LI-DEGs’ and ‘IO-DEGs’ are intersected. A gene is determined to be ‘progressive-up’ when the gene is upregulated both in ‘LI-DEGs’ and ‘IO-DEGs’. A gene is defined as ‘progressive-down’ when the gene is downregulated both in ‘LI-DEGs’ and ‘IO-DEGs’. A gene is ‘initial-up’ when the gene is upregulated in ‘LI-DEGs’ but not in ‘IO-DEGs’. A gene is ‘initial-down’ when the gene is downregulated in ‘LI-DEGs’ but not in ‘IO-DEGs’. A gene is ‘later-up’ when the gene is not upregulated in ‘LI-DEGs’ but is upregulated in ‘IO-DEGs’. A gene is ‘later-down’ when the gene is not downregulated in ‘LI-DEGs’ but is downregulated in ‘IO-DEGs. A gene is ‘up-to-down’ when the gene is upregulated in ‘LI-DEGs’ and downregulated in ‘IO-DEGs’ and ‘down-to-up’ when the reverse applies.

Additional file 1: Figure S1. Schematic of the identification of the four different classes of DEGs‘Class I: AC-DEGs’ are identified from O-AC expression divided by L-AC expression, ‘Class II: preAC-DEGs’ are from O-preAC expression divided by L-preAC expression, Class III: ‘Lean_Ag-DEGs’ are from L-AC expression divided by L-preAC expression, and Class IV: ‘Obese_Ag-DEGs’ are from O-AC expression divided by O-preAC expression. The statistical criteria for detecting each of the DEGs are explained in ditional file 2: Table S1. ‘e[]’ indicates the expression levels of genes within the bracket.

OBJECTIVES We aimed to identify the optimal lower limb position for an ultrasound (US)-guided anterior approach to a sciatic nerve block. METHODS We included 45 patients who met the following criteria: American Society of Anesthesiologists physical status of 1 to 3, age between 18 and 80 years, and scheduled to undergo knee surgery that required a sciatic nerve block. The lower limbs of each patient were placed in the following 4 positions: N, neutral; ER, external rotation of the hip (angle, 45°); ER/F15, ER (angle, 45°) and flexion (angle, 15°) of the hip; and ER/F45, ER (angle, 45°) and F (angle, 45°) of the hip. An investigator acquired US scans of the sciatic nerve in each position, and the visibility score and depth of the sciatic nerve from the skin were analyzed. RESULTS The visibility scores were significantly higher in positions ER/F15 and ER/F45 than in positions ER and N (P

Remote ischemic preconditioning (RIPC) is known to have a protective effect against hepatic ischemia-reperfusion (IR) injury in animal models. However, the underlying mechanism of action is not clearly understood. This study examined the effectiveness of RIPC in a mouse model of hepatic IR and aimed to clarify the mechanism and relationship of the ATP-sensitive potassium channel (KATP) and HMGB1-induced TLR4/MyD88/NF-&kappa, B signaling. C57BL/6 male mice were separated into six groups: (i) sham-operated control, (ii) IR, (iii) RIPC+IR, (iv) RIPC+IR+glyburide (KATP blocker), (v) RIPC+IR+diazoxide (KATP opener), and (vi) RIPC+IR+diazoxide+glyburide groups. Histological changes, including hepatic ischemia injury, were assessed. The levels of circulating liver enzymes and inflammatory cytokines were measured. Levels of apoptotic proteins, proinflammatory factors (TLR4, HMGB1, MyD88, and NF-&kappa, B), and I&kappa, B&alpha, were measured by Western blot and mRNA levels of proinflammatory cytokine factors were determined by RT-PCR. RIPC significantly decreased hepatic ischemic injury, inflammatory cytokine levels, and liver enzymes compared to the corresponding values observed in the IR mouse model. The KATP opener diazoxide + RIPC significantly reduced hepatic IR injury demonstrating an additive effect on protection against hepatic IR injury. The protective effect appeared to be related to the opening of KATP, which inhibited HMGB1-induced TRL4/MyD88/NF-kB signaling.

Recent studies have reported the advantages of spinal anesthesia over general anesthesia in orthopedic patients. However, little is known about the relationship between acute kidney injury (AKI) after total knee arthroplasty (TKA) and anesthetic technique. This study aimed to identify the influence of anesthetic technique on AKI in TKA patients. We also evaluated whether the choice of anesthetic technique affected other clinical outcomes. We retrospectively reviewed medical records of patients who underwent TKA between January 2008 and August 2016. Perioperative data were obtained and analyzed. To reduce the influence of potential confounding factors, propensity score (PS) analysis was performed. A total of 2809 patients and 2987 cases of TKA were included in this study. A crude analysis of the total set demonstrated a significantly lower risk of AKI in the spinal anesthesia group. After PS matching, the spinal anesthesia group showed a tendency for reduced AKI, without statistical significance. Furthermore, the spinal anesthesia group showed a lower risk of pulmonary and vascular complications, and shortened hospital stay after PS matching. In TKA patients, spinal anesthesia had a tendency to reduce AKI. Moreover, spinal anesthesia not only reduced vascular and pulmonary complications, but also shortened hospital stay.

Alterations in DNA methylation and gene expression have been implicated in the development of human dilated cardiomyopathy (DCM). Differentially methylated probes (DMPs) and differentially expressed genes (DEGs) were identified between the left ventricle (LV, a pathological locus for DCM) and the right ventricle (RV, a proxy for normal hearts). The data in this DiB are for supporting our report entitled “Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy” (Bong-Seok Jo, In-Uk Koh, Jae-Bum Bae, Ho-Yeong Yu, Eun-Seok Jeon, Hae-Young Lee, Jae-Joong Kim, Murim Choi, Sun Shim Choi, 2016) [1].

Nefopam hydrochloride is a centrally acting compound that induces antinociceptive and antihyperalgesic properties in neuropathic pain models. Previous reports have shown that activation of adenosine triphosphate (ATP)-sensitive and calcium-activated potassium (KATP and KCa2+) channels has antiallodynic effects in neuropathic pain. In the present study, we evaluated the relationship between potassium channels and nefopam to determine whether the antiallodynic effects of nefopam are mediated by potassium channels in a neuropathic pain model.Mechanical allodynia was induced by spinal nerve ligation (SNL) in rats, and the paw withdrawal threshold (PWT) was evaluated by the use of von Frey filaments. Nefopam was administered intraperitoneally before or after SNL. We assessed the relationship between nefopam and intrathecal injection of the KCa2+ channel antagonists apamin and charybdotoxin, and the KATP channel blocker glibenclamide to assess their abilities to reverse the antiallodynic effects of nefopam. In addition, we evaluated whether the KATP channel opener pinacidil had antiallodynic effects and promoted the antiallodynic effects of nefopam.Administration of nefopam before and after SNL induced significant antiallodynic effects (P.01, respectively), which were significantly reduced by glibenclamide (P.01). Pinacidil improved the antiallodynic effects of nefopam (P.01); however, apamin and charybdotoxin had little effects on the antiallodynic properties of nefopam.The antiallodynic effects of nefopam are increased by a KATP channel agonist and reversed by a KATP channel antagonist. These data suggest that the KATP channel is involved in the antiallodynic effects of nefopam in a neuropathic pain model.

This study investigated whether the promoter region of DNA methylation positively or negatively regulates tissue-specific genes (TSGs) and if it correlates with disease pathophysiology. We assessed tissue specificity metrics in five human tissues, using sequencing-based approaches, including 52 whole genome bisulfite sequencing (WGBS), 52 RNA-seq, and 144 chromatin immunoprecipitation sequencing (ChIP-seq) data. A correlation analysis was performed between the gene expression and DNA methylation levels of the TSG promoter region. The TSG enrichment analyses were conducted in the gene&ndash, disease association network (DisGeNET). The epigenomic association analyses of CpGs in enriched TSG promoters were performed using 1986 Infinium MethylationEPIC array data. A correlation analysis showed significant associations between the promoter methylation and 449 TSGs&rsquo, expression. A disease enrichment analysis showed that diabetes- and obesity-related diseases were high-ranked. In an epigenomic association analysis based on obesity, 62 CpGs showed statistical significance. Among them, three obesity-related CpGs were newly identified and replicated with statistical significance in independent data. In particular, a CpG (cg17075888 of PDK4), considered as potential therapeutic targets, were associated with complex diseases, including obesity and type 2 diabetes. The methylation changes in a substantial number of the TSG promoters showed a significant association with metabolic diseases. Collectively, our findings provided strong evidence of the relationship between tissue-specific patterns of epigenetic changes and metabolic diseases.

Purpose: Uterine fibroid embolization (UFE) is associated with post-procedural pain and nausea. In this double-blind randomized controlled study, we compared pre-procedure intravenous (IV) acetaminophen/ibuprofen to postprocedure IV ketorolac in UFE patients. Methods: After institutional review board approval, UFE candidates 21-60 years old were screened and randomly assigned to one of four arms: acetaminophen (1 g), ibuprofen (800 mg), acetaminophen (1 g) and ibuprofen (800 mg) combined, and an active comparator, ketorolac (30 mg). All received rescue patient-controlled hydromorphone for 24 h post-procedure. Primary outcome was measurement of pain intensity (visual analog scale: VAS) between the acetaminophen/ibuprofen group and the ketorolac group. The secondary outcomes were opioid and anti-emetic requirements and nausea intensity (VAS). Results: 40 subjects were analysed: acetaminophen/ ibuprofen (N=16); acetaminophen (N=4); ibuprofen (N=4); ketorolac (N=16). The maximum and mean VAS scores for pain were not different between the acetaminophen/ ibuprofen group and the ketorolac group without adjusting for opioid consumption (p=0.243 and p=0.208, respectively). Total opioid consumption in morphine equivalents (mean [±SE]) was 28.09 mg (±4.58) in the acetaminophen/ibuprofen group and 40.33 mg (±7.79) in the ketorolac group (p=0.087), demonstrating a trend favouring the acetaminophen/ibuprofen group. The mean and maximum nausea scores showed a trend and significant difference (p=0.095 and p=0.003), respectively, favouring the ketorolac group. Conclusion: IV acetaminophen/ibuprofen demonstrated comparable pain control, although there was less opioid requirement for the acetaminophen/ibuprofen group compared to the ketorolac group. Maximum nausea scores were significantly increased with similar ondansetron requirements. Therefore, antiemetic prophylaxis is needed regardless of group.

Background: Degenerative lumbar spinal stenosis is one of the most common causes of chronic lower back pain and radiculopathy. Spinal stenosis is anatomically classified as central and lateral spinal canal stenosis. Many treatment modalities and techniques, including surgery and epidural injection, have been used to manage the pain. However, the effect of hypertonic saline injection via the transforaminal approach has not yet been studied. Objectives: The aim of this study is to determine the effect of adding hypertonic saline to conventional transforaminal epidural steroid injections (TFEI) to provide pain relief for chronic radiculopathy patients secondary to lateral canal spinal stenosis. Study Design: A double-blind, randomized, active-control trial. Setting: An interventional pain management practice in a hospital, Republic of Korea. Methods: Two groups: the hypertonic group received hypertonic saline combined with triamcinolone and the control group received normal saline combined with triamcinolone. A total of 68 patients were randomly allocated into either 2 groups by a computergenerated randomization program. Twenty-seven patients in the hypertonic group and 26 patients in the control group were assessed. A total of 53 patients were included in this analysis. Outcome measures were taken at baseline, one, 2, 3, 4, and 6 months postprocedure. The primary outcome measures included the numerical rating scale (NRS) and the proportion of substantial responders. The secondary outcome measures included the Oswestry disability index (ODI), the proportion of substantial and moderate responders, and patient satisfaction. Results: Transforaminal epidural injection of steroids, with or without the addition of 10% hypertonic saline, was effective and provided significant pain relief with the improvement of functional outcome within 4 months. The addition of hypertonic saline was superior in efficacy compared with conventional TFEI at 3 months follow-up. The differences in the absolute pain scores did not demonstrate statistical significance between the 2 groups. The reduction in pain intensity from the baseline was greater in the hypertonic group and demonstrated higher rates of satisfaction. The use of hypertonic saline also extended the duration of significant pain relief to 6 months compared with baseline. Limitations: The lack of placebo group and small sample size. Conclusion: Superior short-term pain relieving efficacy, but limited long-term effects of hypertonic saline, when added to TFEIs. Key words: Chronic pain, lumbar radiculopathy, lateral canal, spinal stenosis, transforaminal, epidural steroid injections, hypertonic saline, local anesthetic

Background: Lumbar spinal stenosis is a common condition in the elderly. Although balloon treatment is a well-known therapeutic method in specific pain conditions, applying the balloon treatment in patients with lumbar spinal stenosis is not yet well established. Objectives: We tested the therapeutic effect of transforaminal balloon treatment with a Fogarty balloon catheter on body pain and functional performance in patients with severe lumbar spinal stenosis. Study Design: Prospective, randomized, double-blinded, active control trial. Setting: A tertiary, interventional pain management practice, specialty referral center. Methods: Sixty-two patients with refractory unilateral radiculopathy aggravated by walking were enrolled and randomly assigned to receive transforaminal steroid injection after transforaminal balloon treatment using a 3 Fr balloon catheter (n = 32) or the same procedure without balloon treatment (n = 30). The patients were prohibited from making any alterations to their medications during the 12 weeks of their follow-up period. After the first 12 weeks, the patients who had persistent symptoms or unbearable pain were allowed to increase the dose of analgesics or to receive additional interventional treatment. Outcome Assessment: Visual analogue scale (VAS) pain scores for the leg and lower back, Oswestry disability index (ODI), and claudication distance were measured at 2, 4, 8, and 12 weeks post procedure. During the 52 weeks of the overall follow-up period, the patients achieving ≥ 50% leg pain relief without additional treatment or increasing the dose of analgesics were evaluated. Results: Significant improvement occurred compared to baseline in VAS (P < 0.001), ODI (P < 0.001), and claudication distance (P < 0.001) in the balloon group during the overall follow-up period, whereas the improvement in ODI (P < 0.05) and claudication distance (P < 0.05) in the control group persisted for 8 weeks. The balloon group showed better improvement in leg VAS (P < 0.05), ODI (P < 0.05), and claudication distance (P < 0.05) than the control group at all post-procedure assessment points. Kaplan-Meier analysis of the duration of the patients achieving ≥ 50% leg pain relief without additional treatment or increasing the dose of analgesics showed a significant intergroup difference between the balloon and control (P = 0.003) groups. Six patients (18.8%) in balloon group maintained > 50% pain relief for 52 weeks whereas no patient (0%) did in control group. Limitations: Our study is an active-controlled randomized design with a relatively small number of patients. Conclusion: Transforaminal balloon treatment leads to both significant pain relief and functional improvement in a subset of patients with refractory spinal stenosis. Institutional Review: This study was approved by the Institutional Review Board of the Asan Medical Center. Key words: Neurogenic claudication, lumbar foraminal stenosis, transforaminal balloon treatment, Fogarty catheter

Background: Chronic lower back pain with or without radiculopathy represents an important medical, social, and economic problem. Many treatment modalities and techniques, including surgery and epidural administration of steroids, have been used to manage this pain. Hypertonic saline, which has been used as an adjunct to percutaneous epidural adhesiolysis, can also be injected via a transforaminal approach in expectation of longer-lasting effects. Objectives: This study aimed to determine the effect of adding hypertonic saline to conventional transforaminal epidural steroid injections (TFEI) to provide pain relief for chronic radiculopathy patients. Study Design: A retrospective study. Setting: Pain clinic of a university hospital. Methods: Between January 2010 and December 2013, the medical records of 246 patients (94 in the hypertonic group, 153 in the control group) who received transforaminal epidural block were reviewed and analyzed. The hypertonic group received 10% sodium chloride solution added to lidocaine, triamcinolone, and hyaluronidase. Outcomes on pain reduction were measured using a numerical rating scale (NRS) and the responder rate at baseline, one, 3, and 6 months after procedure. Results: The estimated difference in NRS scores from baseline throughout a 6-month followup period in the hypertonic group were significantly higher (P = 0.0003). The proportion of substantial responders (41.9% vs. 34.6% at one month, 40.9% vs. 26.8% at 3 months, and 33.3% vs. 14.4% at 6 months, respectively, P = 0.0058) and substantial/moderate responders (71.0% vs. 58.8% at one month, 65.6% vs. 40.4% at 3 months, and 48.4% vs. 20.3% at 6 months, respectively, P < 0.0001) were significantly higher in the hypertonic group. The Oswestry disability index (ODI) was not different between the groups (P = 0.2697). Limitations: Retrospective design without a control group. Conclusions: Hypertonic saline provides more superior and longer lasting pain relieving effects when added to TFEIs. Key words: Back pain, epidural injections, epidural steroids, hypertonic saline, lumbar, radiculopathy, transforaminal

The cg07814318 hypermethylation of Kruppel-like factor 13 (KLF13) gene has been reported for its relevancy with Body Mass Index (BMI) from European origin. We explored the cg07814318 methylation and its cis-meQTL (cis-methylation quantitative loci) of KLF13 from a childhood obesity cohort. The cg07814318 methylation in blood was significantly associated with obesity and correlated with several obesity-related physical and biochemical traits. We examined the same loci from purified three human cell types (n = 47), i.e., pre-adipocytes, adipocytes and islets. The cg07814318 methylation pattern in pre-adipocytes and islets were significant higher in cells from subjects with a higher BMI compared with control subjects. By exome sequencing of KLF13 gene in blood with the same cohort, we found nine SNPs (single nucleotide polymorphisms) within its gene body, and two SNPs (rs11537749 and rs12595641) were as cis-meQTL of cg07814318. There was the 2.01% methylation change of cg07814318 between homozygous dominant and recessive genotypes, especially, in rs12595641. The sequencing variations within KLF13 genes could drive dynamic modifications of obesity-related CpG methylation. Differential DNA methylation patterns in the KLF13 gene determined from separate blood samples showed that this criterion could be used as a surrogate for representing overall epigenetic changes in cells related to obesity.

Background. Lower back pain is a common reason for disability and the most common cause is lumbar disc herniation. Percutaneous epidural adhesiolysis has been applied to relieve pain and increase the functional capacity of patients who present this condition.Objectives. In this study, we retrospectively evaluated the factors which predict the outcome of percutaneous epidural adhesiolysis in patients who were diagnosed with lumbar disc herniation.Methods. Electronic medical records of patients diagnosed with lumbar disc herniation who have received percutaneous epidural adhesiolysis treatment were reviewed. The primary outcome was the factors that were associated with substantial response of ≥4 points or ≥50% of pain relief in the numerical rating scale pain score 12 months after the treatment.Results. Multivariate logistic regression analysis demonstrated that the presence of high-intensity zone (HIZ) at magnetic resonance imaging was a predictor of substantial response to percutaneous epidural adhesiolysis for 12 months (P=0.007). The presence of a condition involving the vertebral foramen was a predictor for unsuccessful response after 12 months (P=0.02).Discussion and Conclusion. The presence of HIZ was a predictor of favorable long-term outcome after percutaneous epidural adhesiolysis for the treatment of lower back pain with radicular pain caused by lumbar disc herniation.

Dilated cardiomyopathy (DCM) is one of the main causes of heart failure (called cardiomyopathies) in adults. Alterations in epigenetic regulation (i.e., DNA methylation) have been implicated in the development of DCM. Here, we identified a total of 1828 differentially methylated probes (DMPs) using the Infinium 450K HumanMethylation Bead chip by comparing the methylomes between 18 left ventricles and 9 right ventricles. Alterations in DNA methylation levels were observed mainly in lowly methylated regions corresponding to promoter-proximal regions, which become hypermethylated in severely affected left ventricles. Subsequent mRNA microarray analysis showed that the effect of DNA methylation on gene expression regulation is not unidirectional but is controlled by the functional sub-network context. DMPs were significantly enriched in the transcription factor binding sites (TFBSs) we tested. Alterations in DNA methylation were specifically enriched in the cis-regulatory regions of cardiac development genes, the majority of which are involved in ventricular development (e.g., TBX5 and HAND1).

Background: Elderly patients visiting pain clinic may be at greater risk of misunderstanding the explanation because of age-related cognitive decline. Video instruction may provide a consistent from of teaching in a visual and realistic manner. We evaluated the effect of educational video on the patient understanding and satisfaction in a group of geriatric patients visiting pain clinic. Methods: Ninety two patients aged more than 60 years old who were scheduled for transforaminal epidural block were recruited. After exposure to either video or paper instruction process, each patient was asked 5-item comprehension questions, overall satisfaction and preference question. During follow-up period, number of outpatient referral-line call for further explanation was counted. Results: We observed significantly better comprehension in the video education compared with paper instruction (P ＜ 0.001). Patient satisfaction was also higher in the video group (P = 0.015), and patients visiting pain clinic were more preferred video instruction (P ＜ 0.001). Proportion of referral-line call for further explanation were similar (P = 0.302). Conclusions: Video approach to instruction process before consent improves treatment comprehension in geriatric patient visiting pain clinic. (Korean J Pain 2012; 25: 254-257)

Green Design is mostly discussed in the field of industry design on the concept basis, while less attention to environmental issues have been paid by neither designer nor manufacturer, which thereby adds to the necessity of the study on Green Design methods and process to a great extent. This article through the classification and analysis of DFX, researches on which kinds of designs in the Clock products market are invested with green design concept as piloted by the principle of DFMs, DFR, DFA and DFD. DFX means design for excellence, and also "design for X", where X is a variable with many values. Under the label Design for X, a wide collection of specific design guidelines are summarized. This article conducts DFX principle assessments on Clock by selecting 30 products of Clock market varieties as the samples, and conducts the field design practices centering on those materials of the least conformity with green design tenet amidst the Framework assessment results. In the course of field practices, DFMs principle is introduced, and embodies the significance of DFX method guidance by virtue of the ultimate results of conceptual designs conducted in the guidance of theoretical basis.

It is well established that the IFN-gamma/STAT1 pathway plays an important role in the pancreatic beta-cell apoptosis that is observed in STZ-induced type 1 diabetes; however, the upstream regulatory proteins involved have not been understood. Here, we investigated whether activating transcription factor 3 (ATF3) affects STAT1-mediated beta-cell dysfunction and apoptosis in streptozotocin-treated mice. To this, STZ (80 mg/kg, i.p.) was administered to wild-type and STAT1(-/-) or IFN-gamma(-/-) mice for 5 days and the mice were euthanized after 14 days. STZ-induced beta-cell dysfunction and apoptosis were associated with increased STAT1/IRF-1 and ATF3 expression and were correlated with elevated IFN-gamma levels. Genetic depletion using IFN-gamma(-/-) or STAT1(-/-) mice strongly inhibited the reduction of islet cell mass or insulin synthesis/secretion and the increase of beta-cell apoptosis observed in STZ-treated wild-type mice. ATF3 overexpression, especially the C-terminal domain, strongly enhanced beta-cell dysfunction and apoptosis by enhancing STAT1 activation and its accumulation, which were abolished with an ATF3-specific siRNA or C-terminal-deleted ATF3. The STZ induction of ATF3 was completely depleted in IFN-gamma(-/-) mice, but not in STAT1(-/-) mice. Furthermore, STAT1 did not affect ATF3 expression, but STAT1 depletion or its inactivation inhibited STZ-induced ATF3 nuclear translocation and beta-cell apoptosis. Interestingly, ATF3 also increased STAT1 transcription by directly binding to a putative binding region (-116 to -96 bp) in the STAT1 promoter. Our results suggest that ATF3 functions as a potent upstream regulator of STAT1 and ATF3 may play a role in STZ-induced beta-cell dysfunction by enhancing the steady state abundance of STAT1.

Corrective surgery with a posterior approach for adolescent idiopathic scoliosis (AIS) is often accompanied by considerable bleeding. Massive transfusion after excessive hemorrhage is associated with complications such as hypothermia, coagulopathy, and acid–base imbalance. Therefore, predict

Adiponectin acts as an insulin-sensitizing adipokine that protects against obesity-linked metabolic disease, which is generally associated with endoplasmic reticulum (ER) stress. The physiological effects of adiponectin on energy metabolism in the liver are mediated by its receptors. We found that the hepatic expression of adiponectin receptor 2 (AdipoR2) was lower, but the expression of markers of the ER stress pathway, 78 kDa glucose-regulated protein (GRP78) and activating transcription factor 3 (ATF3), was higher in the liver of ob/ob mice compared with control mice. To investigate the regulation of AdipoR2 by ER stress, we added thapsigargin, an ER stress inducer, to a human hepatocyte cell line, HepG2. Addition of the ER stress inducer increased the levels of GRP78 and ATF3, and decreased that of AdipoR2, whereas addition of a chemical chaperone, 4-phenyl butyric acid (PBA), could reverse them. Up- or down-regulation of ATF3 modulated the AdipoR2 protein levels and AdipoR2 promoter activities. Reporter gene assays using a series of 5′-deleted AdipoR2 promoter constructs revealed the location of the repressor element responding to ER stress and ATF3. In addition, using electrophoretic mobility shift and chromatin immunoprecipitation assays, we identified a region between nucleotides −94 and −86 of the AdipoR2 promoter that functions as a putative ATF3-binding site in vitro and in vivo. Thus, our findings suggest that the ER stress-induced decrease in both protein and RNA of AdipoR2 results from a concomitant increase in expression of ATF3, which may play a role in the development of obesity-induced insulin resistance and related ER stress in hepatocytes.

A gene (PH0311) encoding a hypothetical protein from the genome sequence data of the hyperthermophilic archaeon Pyrococcus horikoshii OT3 was cloned and over-expressed in Escherichia coli. The purified recombinant protein was found to possess FAD-dependent NADH oxidase activity, although it lacked sequence homology to any other known general NADH oxidase family. The product of the PH0311 gene was thus designated PhNOX (NADH oxidase from Pyrococcus horikoshii), with an estimated molecular weight of 84 kDa by gel filtration and 22 kDa by SDS-PAGE, indicating it to be a homotetramer of 22 kDa subunits. PhNOX catalyzed the oxidation of reduced β-NADH with subsequent formation of H2O2 in the presence of FAD as a cofactor, but not α-NADH, α-NADPH, or β-NADPH. PhNOX

In human, the telomer-ase plays an important role in cancer. Most somatic cellslack telomerase activity and correspondingly lose telomericDNA, thus are limited their proliferative capacity. Cancercells can overcome this proliferative block through theillegitimate transcriptional up-regulation of the gene encod-ing the catalytic subunit of the enzyme.

Background Resiniferatoxin (RTX) is a potent analog of capsaicin and activates transient receptor potential (TRP) vanilloid type (TRPV) 1. In the current study, we investigated the preventive effect of perineural RTX on the development of cold hypersensitivity induced by spinal nerve ligation (SNL) in rats. Furthermore, we examined the association between the expression level of TRPV1, TRP ankyrin type (TRPA) 1 and TRP melastatin type (TRPM) 8 in the dorsal root ganglion (DRG) and cold hypersensitivity after SNL. Results RTX pretreatment prevented the development of SNL-induced hypersensitivity to mechanical, thermal, and cold stimuli. Western blot analysis 4 weeks after RTX pretreatment showed that RTX pretreatment decreased the protein expression level of SNL-induced TRPM8, but not TRPV1 or TRPA1, in the DRG of SNL rats. Immunofluorescent analysis revealed that up-regulated TRPM8-stained neurons after SNL co-localized with neurofilament 200-positive neurons located in the DRG. Conclusions Pretreatment with perineural RTX significantly inhibits SNL-induced mechanical, thermal, and cold hypersensitivity. The antinociceptive effect of perineural RTX, especially on cold hypersensitivity, may be related to the suppression of TRPM8 expression in DRG. Electronic supplementary material The online version of this article (doi:10.1186/s12868-016-0273-8) contains supplementary material, which is available to authorized users.

Continuously infused phenylephrine is frequently used to reduce the incidence of hypotension in women undergoing cesarean section under spinal anesthesia, but less is known about the prophylactic bolus method. We evaluated three prophylactic bolus doses of phenylephrine during low-dose spinal anesthesia for cesarean section.One-hundred-and-eighty-four patients were randomized to receive 0.9% saline 2mL (Control Group) or phenylephrine 1.0μg/kg (PHE1 Group), 1.5μg/kg (PHE1.5 Group), or 2.0μg/kg (PHE2 Group) immediately after induction of combined spinal-epidural anesthesia. Maternal blood pressure and heart rate were recorded at 1-min intervals until delivery. Hypotension, defined as systolic blood pressure80% of baseline, was treated with rescue doses of phenylephrine 100μg at 1-min intervals until hypotension resolved. The incidence of nausea, vomiting, bradycardia, and hypertension, as well as Apgar scores and umbilical blood gases, were recorded.The incidence of hypotension was 71.7% (33/46) in the Control Group, 68.9% (31/45) in the PHE1 Group, 37.0% (17/46) in the PHE1.5 Group and 45.7% (21/46) in the PHE2 Group (P=0.001). The total rescue dose of phenylephrine was greater in the Control Group than those in the PHE1.5 Group (P0.05) and PHE2 Group (P0.05). The incidence of hypertension increased as the dose of prophylactic phenylephrine increased (P0.001) and was highest in the PHE2 group (37%). Other variables did not differ among the four groups.Under the conditions of this study, prophylactic bolus injection of phenylephrine 1.5μg/kg was a suitable alternative method for reducing the incidence of hypotension during low-dose spinal anesthesia for cesarean section.

Pain is a predictable consequence following operations, but the management of postoperative pain is another challenge for anesthesiologists and inappropriately controlled pain may lead to unwanted outcomes in the postoperative period. Opioids are indeed still at the mainstream of postoperative pain control, but solely using only opioids for postoperative pain management may be connected with risks of complications and adverse effects. As a consequence, the concept of multimodal analgesia has been proposed and is recommended whenever possible. Acetaminophen is one of the most commonly used analgesic and antipyretic drug for its good tolerance and high safety profiles. The introduction of intravenous form of acetaminophen has led to a wider flexibility of its use during peri- and postoperative periods, allowing the early initiation of multimodal analgesia. Many studies have revealed the efficacy, safety and opioid sparing effects of intravenous acetaminophen. Intravenous ibuprofen has also shown to be well tolerated and demonstrated to have significant opioid sparing effects during the postoperative period. However, the number of randomized controlled trials confirming the efficacy and safety is small and should be used in caution in certain group of patients. Intravenous acetaminophen and ibuprofen are important options for multimodal postoperative analgesia, improving pain and patient satisfaction.