3D Bioprinting Strategies for Articular Cartilage Tissue Engineering.

Articular cartilage is the avascular and aneural tissue which is the primary connective tissue covering the surface of articulating bone. Traumatic damage or degenerative diseases can cause articular cartilage injuries that are common in the population. As a result, the demand for new therapeutic options is continually increasing for older people and traumatic young patients. Many attempts have been made to address these clinical needs to treat articular cartilage injuries, including osteoarthritis (OA); however, regenerating highly qualified cartilage tissue remains a significant obstacle. 3D bioprinting technology combined with tissue engineering principles has been developed to create biological tissue constructs that recapitulate the anatomical, structural, and functional properties of native tissues. In addition, this cutting-edge technology can precisely place multiple cell types in a 3D tissue architecture. Thus, 3D bioprinting has rapidly become the most innovative tool for manufacturing clinically applicable bioengineered tissue constructs. This has led to increased interest in 3D bioprinting in articular cartilage tissue engineering applications. Here, we reviewed current advances in bioprinting for articular cartilage tissue engineering.

Enpp2 Expression by Dendritic Cells Is a Key Regulator in Migration.

Enpp2 is an enzyme that catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which exhibits a wide variety of biological functions. Here, we examined the biological effects of Enpp2 on dendritic cells (DCs), which are specialized antigen-presenting cells (APCs) characterized by their ability to migrate into secondary lymphoid organs and activate naïve T-cells. DCs were generated from bone marrow progenitors obtained from C57BL/6 mice. Enpp2 levels in DCs were regulated using small interfering (si)RNA or recombinant Enpp2. Expression of Enpp2 in LPS-stimulated mature (m)DCs was high, however, knocking down Enpp2 inhibited mDC function. In addition, the migratory capacity of mDCs increased after treatment with rmEnpp2; this phenomenon was mediated via the RhoA-mediated signaling pathway. Enpp2-treated mDCs showed a markedly increased capacity to migrate to lymph nodes in vivo. These findings strongly suggest that Enpp2 is necessary for mDC migration capacity, thereby increasing our understanding of DC biology. We postulate that regulating Enpp2 improves DC migration to lymph nodes, thus improving the effectiveness of cancer vaccines based on DC.

Effect of Intra- and Post-Operative Fluid and Blood Volume on Postoperative Pulmonary Edema in Patients with Intraoperative Massive Bleeding.

In patients with intraoperative massive bleeding, the effects of fluid and blood volume on postoperative pulmonary edema are uncertain. Patients with intraoperative massive bleeding who had undergone a non-cardiac surgery in five hospitals were enrolled in this study. We evaluated the association of postoperative pulmonary edema risk and intra- and post-operatively administered fluid and blood volumes in patients with intraoperative massive bleeding. In total, 2090 patients were included in the postoperative pulmonary edema analysis, and 300 patients developed pulmonary edema within 72 h of the surgery. The postoperative pulmonary edema with hypoxemia analysis included 1660 patients, and the condition occurred in 161 patients. An increase in the amount of red blood cells transfused per hour after surgery increased the risk of pulmonary edema (hazard ratio: 1.03; 95% confidence interval: 1.01-1.05; p = 0.013) and the risk of pulmonary edema with hypoxemia (hazard ratio: 1.04; 95% confidence interval: 1.01-1.07; p = 0.024). An increase in the red blood cells transfused per hour after surgery increased the risk of developing pulmonary edema. This increase can be considered as a risk factor for pulmonary edema.

Development and validation of a difficult laryngoscopy prediction model using machine learning of neck circumference and thyromental height.

BACKGROUND: Predicting difficult airway is challengeable in patients with limited airway evaluation. The aim of this study is to develop and validate a model that predicts difficult laryngoscopy by machine learning of neck circumference and thyromental height as predictors that can be used even for patients with limited airway evaluation. METHODS: Variables for prediction of difficulty laryngoscopy included age, sex, height, weight, body mass index, neck circumference, and thyromental distance. Difficult laryngoscopy was defined as Grade 3 and 4 by the Cormack-Lehane classification. The preanesthesia and anesthesia data of 1677 patients who had undergone general anesthesia at a single center were collected. The data set was randomly stratified into a training set (80%) and a test set (20%), with equal distribution of difficulty laryngoscopy. The training data sets were trained with five algorithms (logistic regression, multilayer perceptron, random forest, extreme gradient boosting, and light gradient boosting machine). The prediction models were validated through a test set. RESULTS: The model's performance using random forest was best (area under receiver operating characteristic curve = 0.79 [95% confidence interval: 0.72-0.86], area under precision-recall curve = 0.32 [95% confidence interval: 0.27-0.37]). CONCLUSIONS: Machine learning can predict difficult laryngoscopy through a combination of several predictors including neck circumference and thyromental height. The performance of the model can be improved with more data, a new variable and combination of models.

Dexmedetomidine combined with suprascapular nerve block and axillary nerve block has a synergistic effect on relieving postoperative pain after arthroscopic rotator cuff repair.

PURPOSE: Suprascapular nerve block (SSNB) is the most commonly used block for the relief of postoperative pain from arthroscopic rotator cuff repair and can be used in combination with axillary nerve block (ANB). Dexmedetomidine (DEX) is a type of alpha agonist that can elongate the duration of regional block. The aim of this study was to compare the effects of the use of dexmedetomidine combined with SSNB and ANB with those of the use of SSNB and ANB alone on postoperative pain, satisfaction, and pain-related cytokines within the first 48 h after arthroscopic rotator cuff repair. METHODS: Forty patients with rotator cuff tears who had undergone arthroscopic rotator cuff repair were enrolled in this single-center, double-blinded randomized controlled trial study. Twenty patients were randomly allocated to group 1 and received ultrasound-guided SSNB and ANB using a mixture of 0.5 ml (50 µg) of DEX and 9.5 ml of 0.75% ropivacaine preemptively. The other 20 patients were allocated to group 2 and underwent ultrasound-guided SSNB and ANB alone using a mixture of 0.5 ml of normal saline and 9.5 ml of ropivacaine. The visual analog scale (VAS) for pain and patient satisfaction (SAT) scores were postoperatively checked within 48 h. The plasma interleukin (IL)-6, IL-8, IL-1ß, cortisol, and serotonin levels were also postoperatively measured within 48 h. RESULTS: Group 1 showed a significantly lower mean VAS (visual analog scale of pain) score 1, 3, 6, 12, 18 and 24 h after operation, and a significantly higher mean SAT (patient satisfaction) score 1, 3, 6, 12, 18, 24 and 36 h after the operation than group 2. Group 1 showed a significantly lower mean plasma IL-8 level 1 and 48 h after the operation, and a significantly lower mean IL-1ß level 48 h after the operation than group 2. Group 1 showed a significantly lower mean plasma serotonin level 12 h after the operation than group 2. The mean timing of rebound pain in group 1 was significantly later than that in group 2 (36 h > 23 h, p = 0.007). Six patients each in groups 1 and 2 showed rebound pain. The others did not show rebound pain. CONCLUSIONS: Ultrasound-guided SSNA and ANB with DEX during arthroscopic rotator cuff repair resulted in a significantly lower mean VAS score and a significantly higher mean SAT score within 48 h after the operation than SSNB and ANB alone. Additionally, SSNB and ANB with DEX tended to result in a later mean timing of rebound pain accompanied by significant changes in IL-8, IL-1ß, and serotonin levels within 48 h after the operation. The present study could provide the basis for selecting objective parameters of postoperative pain in deciding the optimal use of medication for relieving pain. LEVEL OF EVIDENCE: Level I. TRIAL REGISTRATION: 2015-20, ClinicalTrials.gov Identifier: NCT04398589. IRB NUMBER: 2015-20, Hallym University Chuncheon Sacred Heart Hospital.

Dexmedetomidine combined with interscalene brachial plexus block has a synergistic effect on relieving postoperative pain after arthroscopic rotator cuff repair.

PURPOSE: Interscalene brachial plexus block (ISB) is one of the most commonly used regional blocks in relieving postoperative pain after arthroscopic rotator cuff repair. Dexmedetomidine (DEX) is an alpha 2 agonist that can enhance the effect of regional blocks. The aim of this study was to compare the effects of DEX combined with ISB with ISB alone on postoperative pain, satisfaction, and pain-related cytokines within the first 48 h after arthroscopic rotator cuff repair. METHODS: Fifty patients with rotator cuff tears who had undergone arthroscopic rotator cuff repair were enrolled in this single center, double-blinded randomized controlled trial study. Twenty-five patients were randomly allocated to group 1 and received ultrasound-guided ISB using a mixture of 1 ml (100 µg) of DEX and 8 ml of 0.75% ropivacaine preemptively. The other 25 patients were allocated to group 2 and underwent ultrasound-guided ISB alone using a mixture of 1 ml of normal saline and 8 ml of ropivacaine. The visual analog scale (VAS) for pain and patient satisfaction (SAT) scores were checked within 48 h postoperatively. The plasma interleukin (IL)-6, -8, -1ß, cortisol, and substance P levels were also measured within 48 h, postoperatively. RESULTS: Group 1 showed a significantly lower mean VAS score and a significantly higher mean SAT score than group 2 at 1, 3, 6, 12, and 18 h postoperatively. Compared with group 2, group 1 showed a significantly lower mean plasma IL-6 level at 1, 6, 12, and 48 h postoperatively and a significantly lower mean IL-8 level at 1, 6, 12, 24, and 48 h postoperatively. The mean timing of rebound pain in group 1 was significantly later than that in group 2 (12.7 h > 9.4 h, p = 0.006). CONCLUSIONS: Ultrasound-guided ISB with DEX in arthroscopic rotator cuff repair led to a significantly lower mean VAS score and a significantly higher mean SAT score within 48 h postoperatively than ISB alone. In addition, ISB with DEX showed lower mean plasma IL-6 and IL-8 levels than ISB alone within 48 h postoperatively, with delayed rebound pain. LEVEL OF EVIDENCE: I. TRIAL REGISTRATION: 2013-112, ClinicalTrials.gov Identifier: NCT02766556.

Comparison of the effect of propofol and desflurane on S-100ß and GFAP levels during controlled hypotension for functional endoscopic sinus surgery: A randomized controlled trial.

BACKGROUND: Although surgical field visualization is important in functional endoscopic sinus surgery (FESS), the complications associated with controlled hypotension for surgery should be considered. Intraoperative hypotension is associated with postoperative stroke, leading to subsequent hypoxia with potential neurologic injury. We investigated the effect of propofol and desflurane anesthesia on S-100ß and glial fibrillary acidic protein (GFAP) levels which are early biomarkers for cerebral ischemic change during controlled hypotension for FESS. METHODS: For controlled hypotension during FESS, anesthesia was maintained with propofol/remifentanil in propofol group (n = 30) and with desflurane/remifentanil in desflurane group (n = 30). For S-100ß and GFAP assay, blood samples were taken at base, 20 and 60 minutes after achieving the target range of mean arterial pressure, and at 60 minutes after surgery. RESULTS: The base levels of S-100ß were 98.04 ±â€Š78.57 and 112.61 ±â€Š66.38 pg/mL in the propofol and desflurane groups, respectively. The base levels of GFAP were 0.997 ±â€Š0.486 and 0.898 ±â€Š0.472 ng/mL in the propofol and desflurane groups, respectively. The S-100ß and GFAP levels were significantly increased in the study period compared to the base levels in both groups (P ≤ .001). There was no significant difference at each time point between the 2 groups. CONCLUSION: On comparing the effects of propofol and desflurane anesthesia for controlled hypotension on the levels of S-100ß and GFAP, we noted that there was no significant difference in S-100ß and GFAP levels between the 2 study groups. CLINICAL TRIAL REGISTRATION: Available at: http://cris.nih.go.kr, KCT0002698.

Association between high-sensitivity cardiac troponin I measured at emergency department and complications of emergency coronary artery bypass grafting.

High-sensitivity cardiac troponin I (hs-cTnI) is a widely used biomarker to identify ischemic chest pain in the Emergency Department (ED), but the clinical impact on emergency coronary artery bypass grafting (eCABG) remains undetermined. We aimed to evaluate the clinical impact of hs-cTnI measured at the ED by comparing outcomes of eCABG in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) which comprises unstable angina (UA) and non-ST-segment-elevation myocardial infarction (NSTEMI). From January 2012 to March 2016, 242 patients undergoing eCABG were grouped according to serum hs-cTnI level in the ED. The primary endpoint was major cardiovascular cerebral event (MACCE) defined as a composite of all-cause death, myocardial infarction, repeat revascularization, and stroke. The incidence of each MACCE composite, in addition to postoperative complications such as acute kidney injury, reoperation, atrial fibrillation, and hospital stay duration were also compared. Patients were divided into two groups: UA [<0.04 ng/mL, n = 102] and NSTEMI [≥0.04 ng/mL, n = 140]. The incidence of MACCE did not differ between the two groups. Postoperative acute kidney injury was more frequent in the NSTEMI group after adjusting for confounding factors (6.9% vs. 23.6%; odds ratio, 2.76; 95% confidence interval, 1.09-6.99; p-value = 0.032). In-hospital stay was also longer in the NSTEMI group (9.0 days vs. 15.4 days, p-value = 0.008). ECABG for UA and NSTEMI patients showed comparable outcomes, but hs-cTnI elevation at the ED may be associated with immediate postoperative complications.

Endovascular repair of subclavian artery injury secondary to internal jugular vein catheterization: case report / Correção endovascular de lesão de artéria subclávia secundária à cateterismo de veia jugular interna: relato de caso

Abstract Background and objectives Ultrasound-guided internal jugular vein catheterization is a common and generally safe procedure in the operating room. However, inadvertent puncture of a noncompressible artery such as the subclavian artery, though rare, may be associated with life-threatening sequelae, including hemomediastinum, hemothorax, and pseudoaneurysm. Case report We describe a case of the successful endovascular repair of right subclavian artery injury in a 75-year-old woman. Subclavian artery was injured secondary to ultrasound-guided right internal jugular vein catheterization under general anesthesia for orthopedic surgery. Conclusion Under general anesthesia several factors such as hypotension can mask the signs of subclavian artery injury. This case report indicates that clinicians should be aware of the complications of central venous catheterization and take prompt action.

Resumo Justificativa e objetivos A cateterização da veia jugular interna guiada por ultrassom é um procedimento comum e geralmente seguro em sala cirúrgica. No entanto, a punção inadvertida de uma artéria não compressível, como a artéria subclávia, embora rara, pode estar associada a sequelas e risco para vida, incluindo hemomediastino, hemotórax e pseudoaneurisma. Relato de caso Descrevemos um caso bem-sucedido da correção endovascular de lesão da artéria subclávia direita em uma paciente de 75 anos. A artéria subclávia foi lesionada após cateterização guiada por ultrassom da veia jugular interna direita sob anestesia geral para cirurgia ortopédica. Conclusão Sob anestesia geral, vários fatores, como a hipotensão, podem mascarar os sinais de lesão da artéria subclávia. Este relato de caso indica que os médicos devem estar cientes das complicações da cateterização venosa central e tomar medidas imediatas.

Pdlim4 is essential for CCR7-JNK-mediated dendritic cell migration and F-actin-related dendrite formation.

Dendritic cells (DCs) are the most potent professional antigen (Ag)-presenting cells and inducers of T cell-mediated immunity. A previous microarray analysis identified PDZ and LIM domain protein 4 (Pdlim4) as a candidate marker for DC maturation. The aim of this study was to investigate whether Pdlim4 influences DC migration and maturation. Mouse bone marrow-derived DCs were transduced lentivirally with Pdlim4 short hairpin RNA and examined by confocal microscopy, flow cytometry, ELISA, and Western blotting. Pdlim4 was highly induced in LPS-stimulated mature DCs (mDCs). Pdlim4-knockdown mDCs showed reduced expression of molecules associated with Ag presentation and T-cell costimulation, reduced cytokine production, and functional defects in their ability to activate T cells. Moreover, Pdlim4 was necessary for mDC migration via C-C chemokine receptor type 7 (CCR7)-JNK in in vitro Transwell assays. The importance of Pdlim4 in DC migration was confirmed with an in vivo migration model in which C57BL/6 mice were injected with fluorescently labeled DCs in the footpad and migration to the popliteal lymph nodes was assessed by flow cytometry. Moreover, dendrite formation in mDCs was remarkably attenuated under Pdlim4 knockdown. Taken together, these results demonstrate that Pdlim4 is necessary for DC migration via CCR7-JNK, dendrite formation, and subsequent development of functional T-cell responses.-Yoo, J.-Y., Jung, N.-C., Lee, J.-H., Choi, S.-Y., Choi, H.-J., Park, S.-Y., Jang, J.-S., Byun, S.-H., Hwang, S.-U., Noh, K.-E., Park, Y., Lee, J., Song, J.-Y., Seo, H. G., Lee, H. S., Lim, D.-S. Pdlim4 is essential for CCR7-JNK-mediated dendritic cell migration and F-actin-related dendrite formation.

[Endovascular repair of subclavian artery injury secondary to internal jugular vein catheterization: case report]. / Correção endovascular de lesão de artéria subclávia secundária à cateterismo de veia jugular interna: relato de caso.

BACKGROUND AND OBJECTIVES: Ultrasound-guided internal jugular vein catheterization is a common and generally safe procedure in the operating room. However, inadvertent puncture of a noncompressible artery such as the subclavian artery, though rare, may be associated with life-threatening sequelae, including hemomediastinum, hemothorax, and pseudoaneurysm. CASE REPORT: We describe a case of the successful endovascular repair of right subclavian artery injury in a 75-year-old woman. Subclavian artery was injured secondary to ultrasound-guided right internal jugular vein catheterization under general anesthesia for orthopedic surgery. CONCLUSION: Under general anesthesia several factors such as hypotension can mask the signs of subclavian artery injury. This case report indicates that clinicians should be aware of the complications of central venous catheterization and take prompt action.

Effects of surgery start time on postoperative cortisol, inflammatory cytokines, and postoperative hospital day in hip surgery: Randomized controlled trial.

BACKGROUND: The aim of this study was to compare morning surgery (Group A), characterized by high cortisol levels, with afternoon surgery (Group B), characterized by low cortisol levels, with respect to cortisol, inflammatory cytokines (interleukin [IL]-6, IL-8), and postoperative hospital days (POHD) after hip surgery. METHODS: The study was conducted in a single center, prospective, randomized (1:1) parallel group trial. Patients undergoing total hip replacement or hemiarthroplasty were randomly divided into two groups according to the surgery start time: 8 AM (Group A) or 1-2 PM (Group B). Cortisol and cytokine levels were measured at 7:30 AM on the day of surgery, before induction of anesthesia, and at 6, 12, 24, and 48 hours (h) after surgery. Visual analogue scale (VAS) and POHD were used to evaluate the clinical effect of surgery start time. VAS was measured at 6, 12, 24, and 48 h postoperatively, and POHD was measured at discharge. RESULTS: In total, 44 patients completed the trial. The postoperative cortisol level was significantly different between the two groups. (24 h, P < .001; 48 h, P < .001). The percentage of patients whose level returned to the initial level was higher in Group B than in Group A (P < .001). Significant differences in IL-6 levels were observed between the two groups at 12, 24, and 48 h after surgery (P = .015; P = .005; P = .002), and in IL-8 levels at 12 and 24 h after surgery (P = .002, P < .001). There was no significant difference between the two groups in VAS and POHD. However, only three patients in Group A were inpatients for more than 3 weeks (P = .233). CONCLUSIONS: Afternoon surgery allowed for more rapid recovery of cortisol to the baseline level than morning surgery, and IL-6 and IL-8 were lower at 1-2 days postoperatively. The results of this study suggest that afternoon surgery may be considered in patients with postoperative delayed wound healing or inflammation because of the difference in cortisol, IL-6 and 8 in according to surgery start time. CLINICAL TRIAL REGISTRATION NUMBER: NCT03076827 (ClinicalTRrial.gov).

The Change of Endotracheal Tube Cuff Pressure During Laparoscopic Surgery.

BACKGROUND: We evaluated the endotracheal tube cuff pressure (Pcuff) changes during pneumoperitoneum for laparoscopic cholecystectomy and the correlations between body mass index (BMI), pneumoperitoneum time, and Pcuff changes. METHODS: Total 60 patients undergoing laparoscopic cholecystectomy were allocated to either a study group (BMI ≥ 25 kg/m2) or a control group (BMI < 25 kg/m2). The endotracheal intubation was performed with a high-volume low-pressure cuffed oral endotracheal tube. A manometer was connected to the pilot balloon using a 3-way stopcock and the cuff was inflated. The change in Pcuff was defined as the difference between the pressure just before intra-abdominal CO2 insufflation and the pressure before CO2 desufflation. RESULTS: Pcuff increased to 5.3 ± 3.6 cmH2O in the study group and 5.7 ± 5.4 cmH2O in the control group. There was no significant difference between two groups. While BMI was not correlated with change in Pcuff (r = 0.022, p = 0.867), there was a significant correlation between change in Pcuff and the duration of pneumoperitoneum (r = 0.309, p = 0.016). CONCLUSION: The change in Pcuff was not affected by BMI and was significantly correlated with pneumoperitoneum time. We recommend regular measurement and adjustment of Pcuff during laparoscopic surgery.

Effects of a Preoperative Transdermal Fentanyl Patch on Proinflammatory Cytokine and Pain Levels During the Postoperative Period: A Randomized Controlled Trial.

OBJECTIVE: The main objectives of this article were to assess the effect of preoperative transdermal fentanyl patch (TFP) on interleukin (IL)-6 and IL-8 levels and pain after laparoscopic cholecystectomy. MATERIALS AND METHODS: Patients received a TFP (25 µg/h) (patch group, n=30) or a placebo patch (control group, n=30) applied 14 hours before operation. After surgery, control group received intravenous continuous fentanyl (25 µg/h) with loading dose (25 µg). IL-6 and IL-8 levels were measured at admission and 1, 6, 12, 24, and 48 hours postoperatively. Pain score and consumption of rescue analgesic were evaluated too. RESULTS: At 24 hours postoperatively, IL-6 and IL-8 reached a peak and then decreased. The peak IL-6 levels were 21.92(±6.22) and 24.91(±6.81) pg/mL in the patch and control group. The significant differences of IL-6 between groups were shown at 6 and 12 hours postoperatively (P=0.032, 0.0001). There were no significant differences in IL-8 levels and pain score. CONCLUSIONS: Preoperative TFP attenuated the increase in IL-6 levels after surgery and provided similar analgesia to continuous fentanyl infusion. Preemptive TFP may have influence on proinflammatory reactions and pain control after surgery.

Is the transdermal fentanyl patch an efficient way to achieve acute postoperative pain control?: A randomized controlled trial.

BACKGROUPD: This study investigated the plasma fentanyl concentration and efficacy of transdermal fentanyl patch (TFP) (25 µg/h) in the management of acute postoperative pain. METHODS: Patients undergoing laparoscopic cholecystectomy were randomly allocated to 2 groups. The TFP group (n = 30) received a single TFP 25 µg/ h to the anterior chest wall 14 h before operation. The IV group (n = 30) received a placebo patch. After the operation, intravenous fentanyl infusion (25 µg/h) was begun with loading dose 25 µg in the IV group and only normal saline in the TFP group. Plasma fentanyl levels were measured at admission, 1, 6, 12, 24, and 48 h postoperatively. Pain severity and adverse effects were evaluated too. RESULTS: The fentanyl level peaked 1 h after operation in the TFP group (3.27 ±â€Š0.34 ng/mL) and 24 h postoperatively in the IV group (2.9 ±â€Š0.42 ng/mL). Pain scores and the use of rescue analgesics were not significantly different between 2 groups. Respiratory depression was not happened in both groups. CONCLUSIONS: The TFP (25 µg/h) affixed 14 h before surgery reached a higher constant concentration than the same dose setting of a constant IV infusion of fentanyl after surgery. Although the concentration of fentanyl was higher than those of previous researches, there was no respiratory depression. But, there was no advantage of reducing pain score and the use of rescue analgesics. CLINICAL TRIAL REGISTRATION: (available at: http://cris.nih.go.kr, KCT0002221).

Changes in the tumor necrosis factor-α level after an ultrasound-guided femoral nerve block in elderly patients with a hip fracture / Alterações no nível de TNF-α após bloqueio do nervo femoral guiado por ultrassom em idosos com fratura de quadril

Abstract Background and objectives: An ultrasound guided femoral nerve block is an established analgesic method in patients with a hip fracture. Elevated cytokine levels correlate with poor patient outcomes after surgery. Hence, the aim of the study was to describe the levels of tumor necrosis factor-α after an ultrasound-guided femoral nerve block in elderly patients having a femoral neck fracture. Methods: A total of 32 patients were allocated into two treatment groups: 16 patients (femoral nerve block group; ultrasound-guided femoral nerve block with up to 20 mL of 0.3 mL.kg−1 of 0.5% bupivacaine and intravenous tramadol) and 16 patients (standard management group; up to 3 mL of 0.9% saline in the femoral sheath and intravenous tramadol). Tumor necrosis factor-α and visual analogue scale scores were evaluated immediately before the femoral nerve block and again at 4, 24, and 48 h after the femoral nerve block. All surgery was performed electively after 48 h of femoral nerve block. Results: The femoral nerve block group had a significantly lower mean tumor necrosis factor-α level at 24 (4.60 vs. 8.14, p < 0.001) and 48 h (5.05 vs. 8.56, p < 0.001) after the femoral nerve block, compared to the standard management group. The femoral nerve block group showed a significantly lower mean visual analogue scale score at 4 (3.63 vs. 7.06, p < 0.001) and 24 h (4.50 vs. 5.75, p < 0.001) after the femoral nerve block, compared to the standard management group. Conclusions: Ultrasound-guided femoral nerve block using 0.3 mL.kg−1 of 0.5% bupivacaine up to a maximum of 20 mL resulted in a significant lower tumor necrosis factor-α level.

Resumo Justificativa e objetivos: O bloqueio do nervo femoral guiado por ultrassom é um método analgésico estabelecido em pacientes com fratura de quadril. Níveis elevados de citocinas estão correlacionados com resultados desfavoráveis para o paciente após a cirurgia. Portanto, o objetivo do estudo foi descrever os níveis do fator de necrose tumoral alfa após bloqueio do nervo femoral guiado por ultrassom em pacientes idosos com fratura do colo de fêmur. Métodos: No total, 32 pacientes foram alocados em dois grupos de tratamento: 16 pacientes (grupo bloqueio do nervo femoral; bloqueio do nervo femoral guiado por ultrassom com até 20 mL de bupivacaína a 0,5% (0,3 mL.kg−1) e tramadol intravenoso) e 16 pacientes (grupo tratamento padrão, até 3 mL de solução salina a 0,9% na bainha femoral e tramadol intravenoso). Os escores do fator de necrose tumoral alfa e da Escala Visual Analógica foram avaliados imediatamente antes do bloqueio do nervo femoral e novamente em 4, 24 e 48 horas pós-bloqueio do nervo femoral. Todas as cirurgias foram realizadas de forma eletiva após 48 horas de bloqueio do nervo femoral. Resultados: O grupo bloqueio do nervo femoral teve um nível médio de fator de necrose tumoral alfa significativamente menor em 24 (4,60 vs. 8,14, p < 0,001) e 48 horas (5,05 vs. 8,56, p < 0,001) pós-bloqueio do nervo femoral, comparado com o grupo tratamento padrão. O grupo bloqueio do nervo femoral apresentou uma média significativamente menor no escore da Escala Visual Analógica em 4 (3,63 vs. 7,06, p < 0,001) e 24 horas (4,50 vs. 5,75, p < 0,001) pós-bloqueio do nervo femoral, em comparação com o grupo tratamento padrão. Conclusões: O bloqueio do nervo femoral guiado por ultrassom utilizando 0,3 mL.kg−1 de bupivacaína a 0,5% até o máximo de 20 mL resultou em um nível significativamente menor de fator de necrose tumoral alfa.

[Changes in the tumor necrosis factor-α level after an ultrasound-guided femoral nerve block in elderly patients with a hip fracture]. / Alterações no nível de TNF­α após bloqueio do nervo femoral guiado por ultrassom em idosos com fratura de quadril.

BACKGROUND AND OBJECTIVES: An ultrasound guided femoral nerve block is an established analgesic method in patients with a hip fracture. Elevated cytokine levels correlate with poor patient outcomes after surgery. Hence, the aim of the study was to describe the levels of tumor necrosis factor-α after an ultrasound-guided femoral nerve block in elderly patients having a femoral neck fracture. METHODS: A total of 32 patients were allocated into two treatment groups: 16 patients (femoral nerve block group; ultrasound-guided femoral nerve block with up to 20mL of 0.3mL.kg-1 of 0.5% bupivacaine and intravenous tramadol) and 16 patients (standard management group; up to 3mL of 0.9% saline in the femoral sheath and intravenous tramadol). Tumor necrosis factor-α and visual analogue scale scores were evaluated immediately before the femoral nerve block and again at 4, 24, and 48h after the femoral nerve block. All surgery was performed electively after 48h of femoral nerve block. RESULTS: The femoral nerve block group had a significantly lower mean tumor necrosis factor-α level at 24 (4.60 vs. 8.14, p<0.001) and 48h (5.05 vs. 8.56, p<0.001) after the femoral nerve block, compared to the standard management group. The femoral nerve block group showed a significantly lower mean visual analogue scale score at 4 (3.63 vs. 7.06, p<0.001) and 24h (4.50 vs. 5.75, p<0.001) after the femoral nerve block, compared to the standard management group. CONCLUSIONS: Ultrasound-guided femoral nerve block using 0.3mL.kg-1 of 0.5% bupivacaine up to a maximum of 20mL resulted in a significant lower tumor necrosis factor-α level.

Rsad2 is necessary for mouse dendritic cell maturation via the IRF7-mediated signaling pathway.

Dendritic cells (DCs) are the most potent professional antigen presenting cells and inducers of T cell-mediated immunity. However, few specific markers of mature DCs (mDC) have been reported. A previous microarray analysis revealed expression of mDC-specific genes and identified Rsad2 (radical S-adenosyl methionine domain containing 2) as a candidate specific marker for DC maturation. Mouse bone marrow-derived DCs were transfected with Rsad2 siRNA and examined by flow cytometry, ELISA, western, and confocal microscopy. C57BL/6 mice received intravenously B16F10 cells to establish a pulmonary metastasis model. Tumor-bearing mice then received subcutaneously two injections of mDCs or Rsad2 knockdown DCs. The cytotoxic T lymphocyte (CTL) population was examined from splenocytes of DC-vaccinated mice by flow cytometry. Rsad2 was induced at high levels in LPS-stimulated mDCs and mDC function was markedly attenuated under conditions of Rsad2 knockdown. Moreover, Rsad2 was necessary for mDC maturation via the IRF7-mediated signaling pathway. The importance of Rsad2 was confirmed in an Rsad2 knockdown lung metastasis mouse model in which mDCs lost their antitumor efficacy. Data on the CTL population further supported the results as above. Taken together, Rsad2 was an obvious and specific marker necessary for DC maturation and these findings will be clearly helpful for further understanding of DC biology.

Comparison of the Efficacy of a Gabapentinoid with an Opioid Versus an Opioid Alone in Patients with Spinal Cord Stimulation.

BACKGROUND: Combination therapy with a gabapentinoid and an opioid improves the quality of life (QOL) of patients with chronic pain. However, the role of combination therapy in patients with spinal cord stimulation (SCS) has not been evaluated. OBJECTIVE: Our primary objective was to evaluate the clinical outcomes of combination therapy consisting of a gabapentinoid and an opioid in patients undergoing SCS. STUDY DESIGN: Retrospective evaluation. SETTING: Veterans Health Service Medical Center, Seoul, Korea. METHODS: We retrospectively reviewed 100 military veteran patients who underwent SCS implantation. Forty-eight of 100 patients had been maintained on SCS for 2 years. Patients were divided into 2 groups by analgesic type: group A (opioid only, n = 20) and group B (opioid + gabapentinoids, n = 28). Pre-implantation information included the numeric rating scale (NRS) pain score, quality of life scale (QOLS) score, and oral morphine equivalents (OMEs). Post-implantation data were obtained at 1, 6, 12, and 24 months. RESULTS: Group B had higher QOLS scores at 1, 6, 12, and 24 months than those of group A (P < 0.05). There were no statistically significant differences in the NRS pain score or OMEs at 1, 6, 12, or 24 months between the 2 groups. LIMITATION: Retrospective design, relatively short follow up period (2 years). CONCLUSION: This study indicated that the addition of a gabapentinoid to an opioid is superior to an opioid alone in terms of QOL in military veteran patients with SCS for 2 years. Combination therapy consisting of a gabapentinoid added to an opioid can be a good modality to improve QOL in patients with SCS. KEY WORDS: Combination, drug therapy, gabapentin, multimodal analgesia, opioid, pain, pregabalin, spinal cord stimulation.

Intraoperative administration of dexmedetomidine reduced the postoperative catheter-related bladder discomfort and pain in patients undergoing lumbar microdiscectomy.

PURPOSE: We aimed to evaluate the effect of the intraoperative dexmedetomidine (DEX) on the incidence and severity of catheter-related bladder discomfort (CRBD) after non-urologic surgery. The secondary aim was to find the correlation between the levels of CRBD and postoperative pain sensation. METHODS: Adult male patients undergoing lumbar microdiscectomy were enrolled. Patients were randomized into two groups. After propofol administration, group D (n = 35) received DEX at a loading dose of 1 µg/kg over 10 min, followed by a continuous infusion of 0.3-0.5 µg/kg/h until the end of surgery. In group C (n = 35), an identical volume of 0.9% saline was infused in the same manner. Induction and maintenance of anesthesia were standardized. The incidence and severity of CRBD, postoperative pain, and adverse effects were assessed at 1, 3, and 6 h after surgery. RESULTS: The incidence of CRBD was significantly lower in group D than in group C at 1 h (34.3 vs. 62.9%, P = 0.017), 3 h (25.7 vs. 60%, P = 0.004), and 6 h (17.1 vs. 54.3%. P = 0.001) postoperatively. The severity of CRBD at 1, 3, and 6 h postoperatively was less in group D than in group C. Postoperative pain score was significantly lower in group D than in group C at 3 and 6 h postoperatively. Adverse events were comparable between two groups. There was a significant correlation between the severity of CRBD and postoperative pain score. CONCLUSIONS: Intraoperative administration of DEX is a safe and effective practice for the prevention of CRBD after lumbar microdiscectomy and can reduce postoperative pain.