Potential Role of Macrophage Polarization in the Progression of Hunner-Type Interstitial Cystitis.

BACKGROUND: Hunner-type interstitial cystitis (HIC) is a chronic inflammatory condition of the bladder. However, it remains unclear whether there is a causal relationship between the presence of Hunner lesions and seemingly normal-appearing areas in the bladder (non-Hunner lesions). This study aimed to investigate the fundamental aspects of HIC by examining potential genetic differences between Hunner and non-Hunner lesions and elucidate their role as potential markers in the progression and suppression of the disease. METHODS: This cross-sectional study enrolled patients with HIC (n = 10) who underwent supratrigonal cystectomy along with augmentation cystoplasty. Full-thickness bladder tissue was collected from Hunner and non-Hunner lesions in the same patient. Normal bladder tissue biopsies were also obtained as controls. Whole transcriptome analysis was performed to analyze the gene expression patterns and immune cell populations. RESULTS: The mucosal layers of patients exhibited similar pathway dysregulation across Hunner and non-Hunner lesions, with immunerelated pathways being prominently affected. In the mucosal layer, genes related to anti-inflammatory and immune suppression were downregulated in Hunner lesions compared to non-Hunner lesions. Moreover, in Hunner lesions, genes related to macrophage differentiation and polarization, such as VSIG4, CD68, MAFB, and LIRB4, were downregulated. The cell fraction of M2 macrophages was found to decrease in Hunner lesions. Immunohistochemical staining revealed an elevated fraction of M1 macrophages and a reduced fraction of M2 macrophages in Hunner lesions compared to those in non-Hunner lesions. In the muscular layer, transcriptomic evidence of muscle thickness was observed in both Hunner and non-Hunner lesions; however, the difference was not significant. CONCLUSION: Hunner lesions showed a reduced expression of anti-inflammatory and immunosuppressive factors compared to non-Hunner lesions, along with alterations in immune cell populations. This study suggests the possibility that macrophage polarization is related to the progression from non-Hunner lesions to Hunner lesions, suggesting its relevance to the characteristics of autoimmune diseases.

Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced gastric cancer.

BACKGROUND: Targeting the DNA damage repair (DDR) pathways is an attractive strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral kinase inhibitor of ataxia telangiectasia and Rad3 related protein, which is a master regulator of DDR. We conducted a phase II trial of ceralasertib plus durvalumab in patients with previously treated advanced gastric cancer (AGC) to demonstrate the safety, tolerability, and clinical activity of the combination. METHODS: This phase II, open-label, single-center, non-randomized study was designed to evaluate the efficacy and safety of ceralasertib in combination with durvalumab in patients with AGC. The study drug regimen was ceralasertib (240 mg two times a day) days 15-28 in a 28-day cycle in combination with durvalumab (1500 mg) at day 1 every 4 weeks. The primary end point was overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (V.1.1). Exploratory biomarker analysis was performed using fresh tumor biopsies in all enrolled patients. RESULTS: Among 31 patients, the ORR, disease control rate, median progression-free survival (PFS), and overall survival were 22.6% (95% CI 9.6% to 41.1%), 58.1% (95% CI 39.1% to 75.5%), 3.0 (95% CI 2.1 to 3.9) months, and 6.7 (95% CI 3.8 to 9.6) months, respectively. Common adverse events were manageable with dose modification. A subgroup of patients with a loss of ataxia telangiectasia mutated (ATM) expression and/or high proportion of mutational signature attributable to homologous repair deficiency (sig. HRD) demonstrated a significantly longer PFS than those with intact ATM and low sig. HRD (5.60 vs 1.65 months; HR 0.13, 95% CI 0.045 to 0.39; long-rank p<0.001). During the study treatment, upregulation of the innate immune response by cytosolic DNA, activation of intratumoral lymphocytes, and expansion of circulating tumor-reactive CD8 +T cell clones were identified in responders. Enrichment of the tumor vasculature signature was associated with treatment resistance. CONCLUSIONS: Ceralasertib plus durvalumab has promising antitumor activity, with durable responses in patients with refractory AGC. Thus, a biomarker-driven trial is required. TRIAL REGISTRATION: NCT03780608.

Metabolic radiogenomics in lung cancer: associations between FDG PET image features and oncogenic signaling pathway alterations.

This study investigated the associations between image features extracted from tumor 18F-fluorodeoxyglucose (FDG) uptake and genetic alterations in patients with lung cancer. A total of 137 patients (age, 62.7 ± 10.2 years) who underwent FDG positron emission tomography/computed tomography (PET/CT) and targeted deep sequencing analysis for a tumor lesion, comprising 61 adenocarcinoma (ADC), 31 squamous cell carcinoma (SQCC), and 45 small cell lung cancer (SCLC) patients, were enrolled in this study. From the tumor lesions, 86 image features were extracted, and 381 genes were assessed. PET features were associated with genetic mutations: 41 genes with 24 features in ADC; 35 genes with 22 features in SQCC; and 43 genes with 25 features in SCLC (FDR < 0.05). Clusters based on PET features showed an association with alterations in oncogenic signaling pathways: Cell cycle and WNT signaling pathways in ADC (p = 0.023, p = 0.035, respectively); Cell cycle, p53, and WNT in SQCC (p = 0.045, 0.009, and 0.029, respectively); and TGFß in SCLC (p = 0.030). In addition, SUVpeak and SUVmax were associated with a mutation of the TGFß signaling pathway in ADC (FDR = 0.001, < 0.001). In this study, PET image features had significant associations with alterations in genes and oncogenic signaling pathways in patients with lung cancer.

Strong and Selective Inhibitory Effects of the Biflavonoid Selamariscina A against CYP2C8 and CYP2C9 Enzyme Activities in Human Liver Microsomes.

Like flavonoids, biflavonoids, dimeric flavonoids, and polyphenolic plant secondary metabolites have antioxidant, antibacterial, antiviral, anti-inflammatory, and anti-cancer properties. However, there is limited data on their effects on cytochrome P450 (P450) and uridine 5'-diphosphoglucuronosyl transferase (UGT) enzyme activities. In this study we evaluate the inhibitory potential of five biflavonoids against nine P450 activities (P450s1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A) in human liver microsomes (HLMs) using cocktail incubation and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The most strongly inhibited P450 activity was CYP2C8-mediated amodiaquine N-dealkylation with IC50 ranges of 0.019~0.123 µM. In addition, the biflavonoids-selamariscina A, amentoflavone, robustaflavone, cupressuflavone, and taiwaniaflavone-noncompetitively inhibited CYP2C8 activity with respective Ki values of 0.018, 0.083, 0.084, 0.103, and 0.142 µM. As selamariscina A showed the strongest effects, we then evaluated it against six UGT isoforms, where it showed weaker inhibition (UGTs1A1, 1A3, 1A4, 1A6, 1A9, and 2B7, IC50 1.7 µM). Returning to the P450 activities, selamariscina A inhibited CYP2C9-mediated diclofenac hydroxylation and tolbutamide hydroxylation with respective Ki values of 0.032 and 0.065 µM in a competitive and noncompetitive manner. However, it only weakly inhibited CYP1A2, CYP2B6, and CYP3A with respective Ki values of 3.1, 7.9, and 4.5 µM. We conclude that selamariscina A has selective and strong inhibitory effects on the CYP2C8 and CYP2C9 isoforms. This information might be useful in predicting herb-drug interaction potential between biflavonoids and co-administered drugs mainly metabolized by CYP2C8 and CYP2C9. In addition, selamariscina A might be used as a strong CYP2C8 and CYP2C9 inhibitor in P450 reaction-phenotyping studies to identify drug-metabolizing enzymes responsible for the metabolism of new chemicals.

Immune subtyping of extranodal NK/T-cell lymphoma: a new biomarker and an immune shift during disease progression.

Extranodal NK/T-cell lymphoma is an aggressive lymphoma that is strongly associated with Epstein-Barr virus infection. Although some extranodal NK/T-cell lymphoma patients have shown responses to immune checkpoint blockade, biomarkers for predicting extranodal NK/T-cell lymphoma patient response to immunotherapy have not yet been defined. To understand the tumor immune microenvironment, we analyzed the expression of 579 immune-related genes and characterized the immune cells using immunohistochemistries and in situ hybridization for EBER. Based on comprehensive analyses, we developed an immune subtyping model that classifies extranodal NK/T-cell lymphoma patients into four tumor immune microenvironment subgroups using three immunohistochemical markers (FoxP3, PD-L1, and CD68). The four tumor immune microenvironment subgroups were named immune tolerance, immune evasion-A, immune evasion-B, and immune silenced. The immune tolerance group was characterized by high-Treg counts and was frequently observed in early stage, and nasal extranodal NK/T-cell lymphoma. The immune evasion group showed high cytotoxic T-cell counts and high PD-L1 expression but low Treg counts. In the immune-silenced group, almost all immune responses were exhausted, most patients were at an advanced stage, and had the poorest disease prognosis among the tumor immune microenvironment subgroups. In some patients (n = 3), a shift in the tumor immune microenvironment subgroup classification was observed in sequential biopsies. The response rate to pembrolizumab, an anti-PD-1 antibody, was 100% (1/1) in the immune tolerance group, 60% (3/5) in the immune evasion group, and 0% (0/5) in the immune-silenced group. We classified extranodal NK/T-cell lymphoma into four tumor immune microenvironment subgroups using a new classification system. In conclusion, we propose that the tumor immune microenvironment of extranodal NK/T-cell lymphoma may change during disease progression and may serve as a useful biomarker for immunotherapy.

Association Between Elevated Echocardiographic Index of Left Ventricular Filling Pressure and Acute Kidney Injury After Off-Pump Coronary Artery Surgery.

BACKGROUND: The ratio of the early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/e') is an echocardiographic index of mean left ventricular (LV) filling pressure. We investigated the association between the preoperative E/e' ratio and postoperative acute kidney injury (AKI) during off-pump coronary artery bypass surgery (OPCAB).Methods and Results:We reviewed 585 patients who underwent OPCAB and with preserved LV ejection fraction determined by preoperative echocardiography. AKI was determined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariable logistic regression analysis was performed. E/e' was also analyzed as 3 categories (E/e' <8, 8≤E/e'≤15, and E/e' >15) and as a continuous variable. A propensity score analysis was used to match the patients with E/e' >15 and E/e' ≤15. A preoperative E/e' >15 was an independent predictor for AKI (odds ratio 3.01, 95% confidence interval 1.40-6.17). E/e' >15 was also an independent predictor for AKI when E/e' was analyzed with 3 categories or as a continuous variable. In the matched sample, the incidence of AKI and 1-year mortality was significantly higher in patients with E/e' >15. CONCLUSIONS: Among patients undergoing OPCAB with preserved LV systolic function, a preoperative E/e' ratio >15 was an independent predictor of postoperative AKI. Measurement of the preoperative E/e' ratio may help to assess the risk of postoperative AKI.

Sulfuretin promotes osteoblastic differentiation in primary cultured osteoblasts and in vivo bone healing.

Although sulfuretin, the major flavonoid of Rhus verniciflua Stokes, has a variety of biological actions, its in vitro and in vivo effects on osteogenic potential remain poorly understood. The objective of the present study was to investigate the effects of sulfuretin on in vitro osteoblastic differentiation and the underlying signal pathway mechanisms in primary cultured osteoblasts and on in vivo bone formation using critical-sized calvarial defects in mice. Sulfuretin promoted osteogenic differentiation of primary osteoblasts, with increased ALP activity and mineralization, and upregulated differentiation markers, including ALP, osteocalcin, and osteopontin, in a concentration-dependent manner. The expression levels of Runx2, BMP-2, and phospho-Smad1/5/8 were upregulated by sulfuretin. Moreover, sulfuretin increased phosphorylation of Akt, mTOR, ERK, and JNK. Furthermore, sulfuretin treatment increased mRNA expression of Wnt ligands, phosphorylation of GSK3, and nuclear ß-catenin protein expression. In vivo studies with calvarial bone defects revealed that sulfuretin significantly enhanced new bone formation by micro-computed tomography and histologic analysis. Collectively, these data suggest that sulfuretin acts through the activation of BMP, mTOR, Wnt/ß-catenin, and Runx2 signaling to promote in vitro osteoblast differentiation and facilitate in vivo bone regeneration, and might be have therapeutic benefits in bone disease and regeneration.

Evaluation of Osteoblast-Like Cell Viability and Differentiation on the Gly-Arg-Gly-Asp-Ser Peptide Immobilized Titanium Dioxide Nanotube via Chemical Grafting.

This study examined the effect of the immobilization of the Gly-Arg-Gly-Asp-Ser (GRGDS) peptide on titanium dioxide (TiO2) nanotube via chemical grafting on osteoblast-like cell (MG-63) viability and differentiation. The specimens were divided into two groups; TiO2 nanotubes and GRGDS-immobilized TiO2 nanotubes. The surface characteristics of GRGDS-immobilized TiO2 nanotubes were observed by using X-ray photoelectron spectroscopy (XPS) and a field emission scanning electron microscope (FE-SEM). The morphology of cells on specimens was observed by FE-SEM after 2 hr and 24 hr. The level of cell viability was investigated via a tetrazolium (XTT) assay after 2 and 4 days. Alkaline phosphatase (ALP) activity was evaluated to measure the cell differentiation after 4 and 7 days. The presence of nitrogen up-regulation or C==O carbons con- firmed that TiO2 nanotubes were immobilized with GRGDS peptides. Cell adhesion was enhanced on the GRGDS-immobilized TiO2 nanotubes compared to TiO2 nanotubes. Furthermore, significantly increased cell spreading and proliferation were observed with the cells grown on GRGDS-immobilized TiO2 nanotubes (P < .05). However, there was no significant difference in ALP activity between GRGDS-immobilized TiO2 nanotubes and TiO2 nanotubes. These results suggest that the GRGDS-immobilized TiO2 nanotubes might be effective in improving the osseointegration of dental implants.

The diagnostic validity of clinical airway assessments for predicting difficult laryngoscopy using a grey zone approach.

OBJECTIVES: The diagnostic validity of clinical airway assessment tests for predicting difficult laryngoscopy in patients requiring endotracheal intubation were evaluated using receiver operating characteristic (ROC) curve analysis and a grey zone approach. METHODS: In this prospective observational study, patients were evaluated during a pre-anaesthetic visit. Predictive airway assessment tests (i.e. Modified Mallampati [MMT] classification; upper lip bite test [ULBT]; mouth opening; sternomental distance; thyromental distance [TMD]; neck circumference; neck mobility; height to thyromental distance [HT/TMD]; neck circumference-to-thyromental distance [NC/TMD]) were performed on each patient and LEMON, Naguib, and MACOCHA scores were also calculated. In addition, laryngeal images were acquired and assessed for percentage of glottic opening (POGO) scores. A POGO score of zero was categorized as difficult laryngoscopy. RESULTS: The incidence of difficult laryngoscopy was 14.4% (35/243). Although seven predictive airway assessments (i.e. MMT classification, ULBT, mouth opening, HT/TMD, NC/TMD, and the LEMON and Naguib models) predicted difficult laryngoscopy by ROC analyses, a grey zone approach showed that the parameters were inconclusive in approximately 70% of patients. From all the tests, the HT/TMD ratio showed the highest sensitivity (80.0%) and ULBT had the highest specificity (95.2%). CONCLUSION: Using the grey zone approach, all predictive airway assessment tests showed large inconclusive zones which may explain previous inconsistent results in the prediction of difficult laryngoscopy. Our results suggest that the usefulness of clinical airway evaluation tests for predicting difficult laryngoscopy remains controversial. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01719848).

Does the Type of Anesthetic Technique Affect In-Hospital and One-Year Outcomes after Off-Pump Coronary Arterial Bypass Surgery?

Despite numerous previous studies, there is little data on the effects of anesthetics on clinical outcome after off-pump coronary arterial bypass grafting (OPCAB). Therefore, we retrospectively compared the effects of anesthetic choice on in-hospital major adverse events (MAEs) and one-year major adverse cardiovascular and cerebral events (MACCEs) in patients undergoing OPCAB. Electronic medical records were reviewed in 192 patients who received propofol-remifenanil total intravenous anesthesia (TIVA) and propensity score-matched 662 patients who received isoflurane anesthesia. The primary endpoints were in-hospital MAEs and one-year MACCEs. The components of in-hospital MAEs were in-hospital death, myocardial infarction (MI), coronary revascularization, stroke, renal failure, prolonged mechanical ventilation longer than 72 h, and postoperative new cardiac arrhythmia requiring treatment. One-year MACCEs was defined as a composite of all-cause mortality, MI, coronary revascularization, and stroke. There was no significant difference in risk of in-hospital MAEs (OR = 1.29, 95% CI = 0.88-1.88, P = 0.20) or one-year MACCEs (OR = 0.81; 95% CI = 0.46-1.42, P = 0.46) between the groups. The risk of postoperative new arrhythmia including new atrial fibrillation significantly increased in the TIVA group compared to the isoflurane anesthesia group (OR = 1.72, 95% CI = 1.12-2.63, P = 0.01). In conclusion, the choice between propofol-remifentanil TIVA and isoflurane anesthesia did not show differences in incidence of in-hospital MAEs or one-year MACCEs in patients undergoing OPCAB. However, further studies on the effects of anesthetics on development of in-hospital new arrhythmia will be needed.

Combined effects of mineral trioxide aggregate and human placental extract on rat pulp tissue and growth, differentiation and angiogenesis in human dental pulp cells.

OBJECTIVE: The aim of this study was to evaluate the combined effects of mineral trioxide aggregate (MTA) and human placental extract (HPE) on cell growth, differentiation and in vitro angiogenesis of human dental pulp cells (HDPCs) and to identify underlying signal transduction mechanisms. In vivo dental pulp responses in rats for a pulp-capping agent were examined. MATERIALS AND METHODS: MTS assay. ALP activity test, alizarin red S staining and RT-PCR for marker genes were carried out to evaluate cell growth and differentiation. HUVEC migration, mRNA expression and capillary tube formation were measured to evaluate angiogenesis. Signal transduction was analysed using Western blotting and confocal microscopy. The pulps of rat maxillary first molars were exposed and capped with either MTA or MTA plus HPE. Histologic observation and scoring were performed. RESULTS: Compared to treatment of HDPCs with either HPE or MTA alone, the combination of HPE and MTA increased cell growth, ALP activity, mineralized nodules and expression of marker mRNAs. Combination HPE and MTA increased migration, capillary tube formation and angiogenic gene expression compared with MTA alone. Activation of Akt, mammalian target of rapamycin (mTOR), p38, JNK and ERK MAPK, Akt, and NF-κB were significantly increased by combining HPE and MTA compared with MTA alone. Pulp capping with MTA plus HPE in rats showed superior dentin bridge formation, odontoblastic layers and dentinal tubules and lower inflammatory cell response, compared to the MTA alone group. CONCLUSIONS: This study demonstrates for the first time that the use of MTA with HPE promotes cell growth, differentiation and angiogenesis in HDPCs, which were associated with mTOR, MAPK and NF-κB pathways. Direct pulp capping with HPE plus MTA showed superior results when compared with MTA alone. Thus, the combination of MTA and HPE may be useful for regenerative endodontics.

Can We Really Predict Postoperative Acute Kidney Injury after Aortic Surgery? Diagnostic Accuracy of Risk Scores Using Gray Zone Approach.

Background Several risk scores have been developed to predict acute kidney injury (AKI) after cardiac surgery. We evaluated the accuracy of eight prediction models using the gray zone approach in patients who underwent aortic surgery. Patients and Methods We retrospectively applied the risk scores of Palomba, Wijeysundera, Mehta, Thakar, Brown, Aronson, Fortescue, and Rhamanian to 375 consecutive adult patients undergoing aortic surgery with cardiopulmonary bypass. The area under the receiver operating characteristic curve (AUC) and gray zone approach were used to evaluate the accuracy of the eight models for prediction of AKI, as defined by the RIFLE criteria. Results The incidence of AKI was 29% (109/375). The AUC for predicting AKI requiring dialysis ranged from 0.66 to 0.84, excluding the score described by Brown et al (0.50). The AUC for predicting the RIFLE criteria of risk and higher ranged from 0.57 to 0.68. The application of gray zone approach resulted in more than half of the patients falling in the gray zone: 275 patients (73%) for Palomba, 221 (59%) for Wijeysundera, 292 (78%) for Mehta, 311 (83%) for Thakar, 329 (88%) for Brown, 291 (78%) for Aronson, 205 (54%) for Fortescue, and 308 (82%) for Rhamanian. Conclusion More than half of the patients in our study sample were in the gray zone of eight scoring models for AKI prediction. The two cutoffs of the gray zone can be used when using risk models. A surgery-specific and more accurate prediction model with a smaller gray zone is required for patients undergoing aortic surgery.

A comparison among infusion of lidocaine and dexmedetomidine alone and in combination in subjects undergoing coronary artery bypass graft: a randomized trial.

BACKGROUND: Previous studies have reported the cardioprotective effect of dexmedetomidine and lidocaine. We compared the effect of lidocaine and dexmedetomidine infusion during off-pump coronary artery bypass graft (OPCAB). METHODS: 153 patients undergoing OPCAB were enrolled. The lidocaine group (n=36, Group LIDO) received an infusion of lidocaine 2 mg/kg/h after bolus 1.5 mg/kg; the dexmedetomidine group (n=40, Group DEX) received dexmedetomidine 0.3-0.7 µg/kg/h; the combined group (n=39, Group Combined) received infusion of both drugs; and the control group (n=38) received nothing. We measured serum creatinine kinase-myocardial band (CK-MB) and cardiac troponin I (cTnI) concentration before and immediately after the surgery, postoperative day (POD)#1 and #2. The complication rate and clinical outcomes were compared. RESULTS: The concentration of cTnI was significantly lower in the Group LIDO and Group Combined than the control group on POD#2. The concentration of CK-MB was significantly lower in the Group LIDO and Group Combined compared to the control group on POD#1 and #2 [CK-MB on POD#1: 7.67 (5.78-11.92) vs. 7.18 (5.01-11.72) vs. 13.19 (6.85-23.87) in the Group LIDO, combined and control, respectively, Group LIDO vs. control: p=0.003, Group Combined vs. control: p=0.015]. The AUC of CK-MB was significantly lower in the Group LIDO and Group Combined than the control group. However, clinical variables including complication rate, ICU stay and one-year mortality were not different. CONCLUSIONS: Lidocaine infused at 2 mg/kg/h, but not dexmedetomidine infused at 0.3-0.7 µg/kg/h reduced postoperative myocardial injury marker levels compared with the control group. However, no other clinical benefits were observed.

Effect of pre-warmed intravenous fluids on perioperative hypothermia and shivering after ambulatory surgery under monitored anesthesia care.

PURPOSE: The aim of this study was to evaluate the effects of pre-warmed (approximately 41 °C) intravenous fluids (IV) on perioperative hypothermia and postoperative shivering in female patients undergoing short, ambulatory urological surgery under monitored anesthesia care (MAC). METHODS: Patients between the ages of 35 and 80 years were randomly assigned to either the pre-warmed (n = 27) or the room temperature (n = 26) group. According to group allocation, either pre-warmed IV fluids that had been stored in a warming cabinet for at least 8 h or room temperature IV fluids were administered intraoperatively up to approximately 600-700 ml, including a bolus infusion of 10 ml/kg within 20 min. Perioperative core temperatures at the tympanic membrane, postoperative shivering, subjective thermal comfort, and the use of forced-air warming interventions in the post-anesthesia care unit (PACU) were recorded. RESULTS: Mean core temperatures were significantly higher in the pre-warmed group than they were in the room temperature group after 10 ml/kg preload fluid was administered, at the end of the operation, and on admission to the PACU (p = 0.004, p = 0.02, and p = 0.008, respectively). The incidence of hypothermia (<36 °C) was significantly lower in the pre-warmed group (n = 4) than in the room temperature group (n = 11, p = 0.035) upon PACU admission. The postoperative shivering incidence was also significantly lower in the pre-warmed group (n = 2) than in the room temperature group (n = 8, p = 0.039). CONCLUSIONS: Infusion of pre-warmed IV fluid improved the postoperative recovery profile by decreasing hypothermia and shivering in female patients undergoing short, ambulatory urological surgery under MAC.

Effect of combined single-injection femoral nerve block and patient-controlled epidural analgesia in patients undergoing total knee replacement.

PURPOSE: Total knee replacement is one of the most painful orthopedic procedures, and effective pain relief is essential for early mobility and discharge from hospital. The aim of this study was to evaluate whether addition of single-injection femoral nerve block to epidural analgesia would provide better postoperative pain control, compared to epidural analgesia alone, after total knee replacement. MATERIALS AND METHODS: Thirty-eight patients received a single-injection femoral nerve block with 0.25% levobupivacaine (30 mL) combined with epidural analgesia (femoral nerve block group) and 40 patients received epidural analgesia alone (control group). Pain intensity and volume of patient-controlled epidural analgesia medication and rescue analgesic requirements were measured in the first 48 hours after surgery at three time periods; 0-6 hours, 6-24 hours, and 24-48 hours. Also, side effects such as nausea, vomiting, and pruritus were evaluated. RESULTS: Median visual analog scale at rest and movement was significantly lower until 48 hours in the femoral nerve block group. Patient-controlled epidural analgesia volume was significantly lower throughout the study period, however, rescue analgesia requirements were significantly lower only up to 6 hours in the femoral nerve block group. The incidences of nausea and vomiting and rescue antiemetic requirement were significantly lower in the femoral nerve block group up to 6 hours. CONCLUSION: The combination of femoral nerve block with epidural analgesia is an effective pain management regimen in patients undergoing unilateral total knee replacement.