Updated guidelines for prescribing opioids to treat patients with chronic non-cancer pain in Korea: developed by committee on hospice and palliative care of the Korean Pain Society.

There are growing concerns regarding the safety of long-term treatment with opioids of patients with chronic non-cancer pain. In 2017, the Korean Pain Society (KPS) developed guidelines for opioid prescriptions for chronic non-cancer pain to guide physicians to prescribe opioids effectively and safely. Since then, investigations have provided updated data regarding opioid therapy for chronic non-cancer pain and have focused on initial dosing schedules, reassessment follow-ups, recommended dosage thresholds considering the risk-benefit ratio, dose-reducing schedules for tapering and discontinuation, adverse effects, and inadvertent problems resulting from inappropriate application of the previous guidelines. Herein, we have updated the previous KPS guidelines based on a comprehensive literature review and consensus development following discussions among experts affiliated with the Committee on Hospice and Palliative Care in the KPS. These guidelines may assist physicians in prescribing opioids for chronic non-cancer pain in adult outpatient settings, but should not to be regarded as an inflexible standard. Clinical judgements by the attending physician and patient-centered decisions should always be prioritized.

Degeneration of oil bodies by rough endoplasmic reticulum -associated protein during seed germination in Cannabis sativa.

Oil bodies serve as a vital energy source of embryos during germination and contribute to sustaining the initial growth of seedlings until photosynthesis initiation. Despite high stability in chemical properties, how oil bodies break down and go into the degradation process during germination is still unknown. This study provides a morphological understanding of the mobilization of stored compounds in the seed germination of Cannabis. The achenes of fibrous hemp cultivar (Cannabis sativa cv. 'Chungsam') were examined in this study using light microscopy, scanning electron microscopy and transmission electron microscopy. Oil bodies in Cannabis seeds appeared spherical and sporadically distributed in the cotyledonary cells. Protein bodies contained electron-dense globoid and heterogeneous protein matrices. During seed germination, rough endoplasmic reticulum (rER) and high electron-dense substances were present adjacent to the oil bodies. The border of the oil bodies became a dense cluster region and appeared as a sinuous outline. Later, irregular hyaline areas were distributed throughout oil bodies, showing the destabilized emulsification of oil bodies. Finally, the oil bodies lost their morphology and fused with each other. The storage proteins were concentrated in the centre of the protein body as a dense homogenous circular mass surrounded by a light heterogeneous area. Some storage proteins are considered emulsifying agents on the surface region of oil bodies, enabling them to remain stable and distinct within and outside cotyledon cells. At the early germination stage, rER appeared and dense substances aggregated adjacent to the oil bodies. Certain proteins were synthesized within the rER and then translocated into the oil bodies by crossing the half membrane of oil bodies. Our data suggest that rER-associated proteins function as enzymes to lyse the emulsifying proteins, thereby weakening the emulsifying agent on the surface of the oil bodies. This process plays a key role in the degeneration of oil bodies and induces coalescence during seed germination.

Efficacy of Pericapsular Nerve Group Block for Pain Reduction and Opioid Consumption after Total Hip Arthroplasty: A Meta-Analysis of Randomized Controlled Trials.

The aim of this study was to conduct a meta-analysis of randomized controlled trials (RCTs) for comparison of the effectiveness of pericapsular nerve group (PENG) block with that of other analgesic techniques for reduction of postoperative pain and consumption of opioids after total hip arthroplasty (THA). A search of records in the PubMed, Embase, and Cochrane Library, and ClinicalTrials.gov databases was conducted in order to identify studies comparing the effect of the PENG block with that of other analgesics on reduction of postoperative pain and consumption of opioids after THA. Determination of eligibility was based on the PICOS (participants, intervention, comparator, outcomes, and study design) criteria as follows: (1) Participants: patients who underwent THA. (2) Intervention: patients who received a PENG block for management of postoperative pain. (3) Comparator: patients who received other analgesics. (4) Outcomes: numerical rating scale (NRS) score and opioid consumption during different periods. (5) Study design: clinical RCTs. Five RCTs were finally included in the current meta-analysis. Significantly lower postoperative opioid consumption at 24 hours after THA was observed in the group of patients who received the PENG block compared with the control group (standard mean difference=-0.36, 95% confidence interval -0.64 to -0.08). However, no significant reduction in NRS score at 12, 24, and 48 hours after surgery and opioid consumption at 48 hours after THA was observed. The PENG block showed better results for opioid consumption at 24 hours after THA compared with other analgesics.

A prospective double-blinded randomized control trial comparing erector spinae plane block to thoracic epidural analgesia for postoperative pain in video-assisted thoracic surgery.

OBJECTIVES: To compare the analgesic efficacies of erector spinae plane (ESP) block and thoracic epidural analgesia (TEA) in video-assisted thoracic surgery (VATS). METHODS: Sixty patients undergoing VATS received patient-controlled TEA with a basal rate of 3 ml/hour (h), a bolus of 3 ml (Group E), or ESP block with programmed intermittent bolus infusions of 15 mL/3 h and a bolus of 5 ml (Group ES) for 2 postoperative days. The primary outcome was to compare pain scores at rest 24 h postoperatively between the 2 groups. Secondary outcomes included NRS score for 48 h, procedural time, dermatomal spread, use of rescue medication, adverse events, and patient satisfaction. RESULTS: Patients with continuous ESP block had a higher NRS score than those with TEA but no statistical difference at a specific time. The dermatomal spread was more extensive in the TEA group than in the ESP block group (p=0.016); cumulative morphine consumption was higher in the ESP block group (p=0.047). The incidence of overall adverse events in the TEA group was higher than in the ESP block group (p=0.045). CONCLUSION: Erector spinae plane block may be inferior to TEA for analgesia following VATS, but it could have tolerable analgesia and a better side effect profile than TEA. Therefore, it could be an alternative to TEA as a component of multimodal analgesia.

Atypical induction of HIF-1α expression by pericellular Notch1 signaling suffices for the malignancy of glioblastoma multiforme cells.

Contact-based pericellular interactions play important roles in cancer progression via juxtacrine signaling pathways. The present study revealed that hypoxia-inducible factor-1α (HIF-1α), induced even in non-hypoxic conditions by cell-to-cell contact, was a critical cue responsible for the malignant characteristics of glioblastoma multiforme (GBM) cells through Notch1 signaling. Densely cultured GBM cells showed enhanced viability and resistance to temozolomide (TMZ) compared to GBM cells at a low density. Ablating Notch1 signaling by a γ-secretase inhibitor or siRNA transfection resensitized resistant GBM cells to TMZ treatment and decreased their viability under dense culture conditions. The expression of HIF-1α was significantly elevated in highly dense GBM cells even under non-hypoxic conditions. Atypical HIF-1α expression was associated with the Notch1 signaling pathway in both GBM and glioblastoma stem cells (GSC). Proteasomal degradation of HIF-1α was prevented by binding with Notch1 intracellular domain (NICD), which translocated to the nuclei of GBM cells. Silencing Notch1 signaling using a doxycycline-inducible Notch1 RNA-interfering system or treatment with chetomin, a HIF pathway inhibitor, retarded tumor development with a significant anti-cancer effect in a murine U251-xenograft model. Using GBM patient tissue microarray analysis, a significant increase in HIF-1α expression was identified in the group with Notch1 expression compared to the group without Notch1 expression among those with positive HIF-1α expression. Collectively, these findings highlight the critical role of cell-to-cell contact-dependent signaling in GBM progression. They provide a rationale for targeting HIF-1α signaling even in a non-hypoxic microenvironment.

TMI-1, TNF-α-Converting Enzyme Inhibitor, Protects Against Paclitaxel-Induced Neurotoxicity in the DRG Neuronal Cells In Vitro.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) negatively impacts cancer survivors' quality of life and is challenging to treat with existing drugs for neuropathic pain. TNF-α is known to potentiate TRPV1 activity, which contributes to CIPN. Here, we assessed the role of TMI-1, a TNF-α-converting enzyme inhibitor, in paclitaxel (PAC)-induced neurotoxicity in dorsal root ganglion (DRG) cells. Materials and Methods: Immortalized DRG neuronal 50B11 cells were cultured and treated with PAC or PAC with TMI-1 following neuronal differentiation. Cell viability, analysis of neurite growth, immunofluorescence, calcium flow cytometry, western blotting, quantitative RT-PCR, and cytokine quantitation by ELISA were performed to determine the role of TMI-1 in neurotoxicity in neuronal cells. Results: PAC administration decreased the length of neurites and upregulated the expression of TRPV1 in 50B11 cells. TMI-1 administration showed a protective effect by suppressing inflammatory signaling, and secretion of TNF-α. Conclusion: TMI-1 partially protects against paclitaxel-induced neurotoxicity by reversing the upregulation of TRPV1 and decreasing levels of inflammatory cytokines, including TNF-α, IL-1ß, and IL-6 in neuronal cells.

Effects of Inhalation versus Total Intravenous Anesthesia on Postoperative Pulmonary Complications after Anatomic Pulmonary Resection.

BACKGROUND: No consensus exists regarding whether volatile anesthetics are superior to intravenous anesthetics for reducing postoperative pulmonary complications (PPCs) in patients undergoing general anesthesia for surgery. Studies of this issue focused on anatomic pulmonary resection are lacking. This study compared the effects of total intravenous anesthesia (TIVA) versus volatile anesthesia on PPCs after anatomic pulmonary resection in patients with lung cancer. METHODS: This retrospective study examined the medical records of patients with lung cancer who underwent lung resection at our center between January 2018 and October 2020. The primary outcome was the incidence of PPCs, which included prolonged air leak, pneumonia, acute respiratory distress syndrome, empyema, atelectasis requiring bronchofiberscopy (BFS), acute lung injury (ALI), bronchopleural fistula (BPF), pulmonary embolism, and pulmonary edema. Propensity score matching (PSM) was used to balance the 2 groups. In total, 579 anatomic pulmonary resection cases were included in the final analysis. RESULTS: The analysis showed no statistically significant difference between the volatile anesthesia and TIVA groups in terms of PPCs, except for prolonged air leak. Neither of the groups showed atelectasis requiring BFS, ALI, BPF, pulmonary embolism, or pulmonary edema after PSM. However, the length of hospitalization, intensive care unit stay, and duration of chest tube indwelling were shorter in the TIVA group. CONCLUSION: Volatile anesthetics showed no superiority compared to TIVA in terms of PPCs after anatomical pulmonary resection in patients with lung cancer. Considering the advantages of each anesthetic modality, appropriate anesthetic modalities should be used in patients with different risk factors and situations.

Peripheral Nerve Block for Hip Arthroscopy Does Not Have any Clinical Advantage Compared With Local Anesthetic Regarding Pain Management: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: To evaluate the efficacy of peripheral nerve block on reduction in opioid consumption and pain control after hip arthroscopy. METHOD: To identify studies evaluating the effects of peripheral nerve block on pain control and reduction in opioid consumption in hip arthroscopy, we searched all records in the PubMed, Embase, and Cochrane Library databases until May 2021. Studies with the following characteristics were considered eligible: 1) patients who underwent a hip arthroscopy (population); 2) patients who received peripheral nerve block (intervention); 3) patients who did not receive peripheral nerve block (comparator); 4) record of total opioid consumption as a primary outcome and pain level at 1, 3 to 6, and 24 hours after surgery, patient satisfaction, and incidence of nausea and vomiting as secondary outcomes (outcomes); and 5) randomized controlled trial (study design). Data were independently extracted by two reviewers and synthesized using a random or fixed-effects model, according to the heterogeneity. RESULTS: Eight RCTs were finally included in the meta-analysis. There were no significant differences in postoperative opioid consumption at 24 hours (standardized mean difference [SMD] = -0.091, 95% confidence interval [CI] [-0.270, 0.089]) or in visual analog scale (VAS) score at 1 (SMD = 0.299, 95% CI [-0.758, 0.160]), 3 to 6 (SMD = -0.304, 95% CI [-0.655, 0.047]), and 24 (SMD = -0.230, 95% CI [-0.520, 0.060]) hours postoperatively between the peripheral nerve block and control groups. Moreover, no significant differences were observed in patient satisfaction (SMD < 0.001, 95% CI [-0.284, 0.284]) or the incidence of nausea and vomiting (SMD = 0.808, 95% CI [0.311, 2.104]) between the two groups. CONCLUSION: Peripheral nerve block for hip arthroscopy has no clinical advantage regarding pain management after surgery when compared with the group that received the local infiltration of analgesics without peripheral nerve block. LEVEL OF EVIDENCE: Level II, meta-analysis of level I and II randomized controlled trials (RCTs).

Transient involuntary movement disorder after spinal anesthesia: A case report.

BACKGROUND: Spinal anesthesia is commonly used for various surgeries. While many complications occur after induction of spinal anesthesia, involuntary movement is an extremely rare complication. CASE SUMMARY: Herein, we report the case of a 54-year-old healthy male patient who experienced involuntary movements after intrathecal injection of local anesthetics. This patient had undergone metal implant removal surgery in both the lower extremities; 7 h after intrathecal hyperbaric bupivacaine administration, involuntary raising of the left leg began to occur every 2 min. When the movement disorder appeared, the patient was conscious and cooperative. No other specific symptoms were noted in the physical examination conducted immediately after the involuntary leg raising started; moreover, the patient's motor and sensory assessments were normal. The symptom gradually subsided. Twelve hours after the symptom first occurred, its frequency decreased to approximately once every three hours. Two days postoperatively, the symptoms had completely disappeared without intervention. CONCLUSION: Anesthesiologists should be aware that movement disorders can occur after spinal anesthesia and be able to identify the cause, such as electrolyte imbalance or epilepsy, since immediate action may be required for treatment. Furthermore, it is crucial to know that involuntary movement that develop following spinal anesthesia is mostly self-limiting and may not require additional costly examinations.

Acute lower extremity arterial thrombosis after intraocular foreign body removal under general anesthesia: A case report and review of literature.

BACKGROUND: Surgery, which is a major risk factor for venous thrombosis, has rarely been considered a risk factor for arterial thrombosis. Recent studies have suggested that venous and arterial thromboses share common risk factors and have a bidirectional relationship. Accordingly, there is a growing interest in the risk of arterial thrombosis after surgery. We report a case of acute bilateral lower extremity arterial thromboses that developed after a prolonged surgery. CASE SUMMARY: A 59-year-old man was hospitalized for intraocular foreign body removal surgery. He was a heavy-drinking smoker and had untreated hypertension and varicose veins in both legs. The operation was unexpectedly prolonged, lasting 4 h and 45 min. Immediately after emergence from general anesthesia, the patient complained of extreme pain in both legs. After the surgical drape was removed, cyanosis was evident in both feet of the patient. The pulse was not palpable, and continuous-wave Doppler signals were inaudible in the bilateral dorsalis pedis and posterior tibial arteries. Computed tomography angiography confirmed acute bilateral thrombotic occlusion of the popliteal arteries, proximal anterior tibial arteries, and tibioperoneal trunks. Arterial pulse returned in both lower limbs after 6 h of heparin initiation. The patient was discharged on postoperative day 26 without any sequelae. CONCLUSION: Acute lower extremity arterial thrombosis can occur after surgery. Anesthesiologists should pay particular attention to patients with risk factors for thrombosis.

Comparison of efficacy between palonosetron-midazolam combination and palonosetron alone for prevention of postoperative nausea and vomiting in patients undergoing breast surgery and patient controlled analgesia: A prospective, randomized, double-blind study: A CONSORT-compliant study.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complaint in patients following general anesthesia. Various antiemetics, including 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, are effective but still have limited efficacy. Therefore, combination therapy is preferable to using a single drug alone in high-risk patients. We performed a comparative study on the antiemetic effect of palonosetron, a 5-HT3 receptor antagonist, monotherapy vs palonosetron-midazolam combination therapy for the prevention of PONV. METHODS: A total of 104 female patients scheduled for breast cancer surgery were enrolled. They were randomly divided into 2 groups, a palonosetron monotherapy group (group P) and palonosetron-midazolam combination therapy group (group PM). Both groups received 0.075 mg palonosetron intravenously after induction of anesthesia. Patient-controlled analgesia (PCA) was applied according to the allocated group. Intravenous (IV)-PCA in group P consisted of fentanyl 20 µg/kg plus normal saline (total volume: 100 ml); IV-PCA in group PM consisted of fentanyl 20 µg/kg plus midazolam 4 mg plus normal saline (total volume: 100 ml). Efficacy parameters were collected during 0 to 1, 1 to 6, 6 to 24, and 24 to 48 hours postoperative time intervals. These measures included complete response (defined as no PONV and no rescue anti-emetic use) rate, incidence of PONV, sedation score, rescue antiemetic use, rescue analgesic use, and numerical rating scale (NRS) for pain. The complete response rate during the 0 to 24 hours interval was analyzed as the primary outcome. RESULTS: Although the complete response rate between 0 and 24 hours was higher in group PM (42.3% and 48.1% in group P and PM, respectively), there was no statistically significant difference (P = .55). The complete response rates in other time intervals were not different between the 2 groups as well. The sedation score and NRS score also showed no differences between the 2 groups. CONCLUSIONS: The combination therapy of palonosetron with midazolam did not lead to a greater reduction in the incidence of PONV than monotherapy in patients undergoing breast surgery and receiving IV-PCA containing fentanyl.

Microvascular Reactivity Measured by Dynamic Near-infrared Spectroscopy Following Induction of General Anesthesia in Healthy Patients: Observation of Age-related Change.

Background: The purpose of this study was to investigate the effect of general anesthesia on microvascular reactivity and tissue oxygen saturation (StO2) using near-infrared spectroscopy in conjunction with vascular occlusion tests (VOT). Age-related changes of microvascular reactivity, that is, the capacity of capillary recruitment, were examined. Methods: This prospective observational study was performed on 60 patients without comorbidities who underwent elective surgery under general anesthesia. Baseline StO2 on thenar eminence, hemodynamics, and laboratory profile were monitored before (T0) and 30 min after general anesthesia (T1). During VOT, occlusion slope representing oxygen consumption of muscle and recovery slope representing microvascular reactivity were also collected at T0 and T1. Results: Baseline StO2 and minimum / maximum StO2 during VOT increased under general anesthesia. Occlusion slope decreased while the recovery slope increased under general anesthesia. To observe aging effect, Receiver operating characteristic analysis was performed and age less than 65 years old showed a fair performance in predicting the increase of microvascular reactivity after the induction of anesthesia (AUC 0.733, 95% CI 0.594-0.845, P= 0.003). For age-related analyses, 27 patients of younger group (< 65 years) and 26 patients of older group (≥ 65 years) were divided. Recovery slope significantly increased under general anesthesia in younger group (2.44 [1.91-2.81] % ∙ sec-1 at T0 and 3.59 [2.58-3.51] % ∙ sec-1 at T1, P <0.001), but not in older group (2.61 [2.21-3.20] % ∙ sec-1 at T0, 2.63 [1.90-3.60] % ∙ sec-1 at T1, P = 0.949). Conclusions: General anesthesia could improve StO2 through increase of microvascular reactivity and decrease of tissue metabolism. However, microvascular reactivity to capillary recruitment under general anesthesia significantly improves in younger patients, not in older patients.

Evaluation of Analytical Performances of Magnetic Force-Assisted Electrochemical Sandwich Immunoassay for the Quantification of Carcinoembryonic Antigen.

Carcinoembryonic antigen (CEA) is a biomarker indicated in different cancers, targeted for quantitative analysis via immunoassay. Here we introduce a new technique called magnetic force-assisted electrochemical sandwich immunoassay (MESIA) for determination of CEA level in a drop of human serum using a fully automated point-of-care testing (POCT) device. The analytical performances of the assay are assessed based on precision, accuracy, limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ), linearity, Hook effect, interference, cross-reactivity, and method comparison following the guidelines of the Clinical Laboratory Standards Institute (CLSI). The LoD is 0.50 ng/ml. A linear relationship is shown in the range of 0.5-200 ng/ml. A high dose effect is not seen up to approximately 500,000 ng/ml. The recovery range is from 94.7 to 108.9%. The %CV of run-to-run and within-lab variations are less than 2.04 and 4.41% across the CEA concentrations, respectively, whereas reproducibility is 4.45-6.24%. Method comparison shows that the assay correlates well with the reference device (R 2 = 0.9884). The assay demonstrates acceptable precision, accuracy, LoB, LoD and LoQ, hook effect, linearity, interference, cross-reactivity, and high correlation with its reference device. Thus, the system is suitable for the quantification of CEA in clinical practices with a POCT manner.

The analgesic efficacy of a single injection of ultrasound-guided retrolaminar paravertebral block for breast surgery: a prospective, randomized, double-blinded study.

BACKGROUND: The thoracic paravertebral block is an effective analgesic technique for postoperative pain management after breast surgery. The ultrasound-guided retrolaminar block (RLB) is a safer alternative to conventional paravertebral block. Thus, we assessed the analgesic efficacy of ultrasound-guided RLB for postoperative pain management after breast surgery. METHODS: Patients requiring breast surgery were randomly allocated to group C (retrolaminar injection with saline) and group R (RLB with local anesthetic mixture). The RLB was performed at the level of T3 with local anesthetic mixture (0.75% ropivacaine 20 mL + 2% lidocaine 10 mL) under general anesthesia before the skin incision. The primary outcome was cumulative morphine consumption using intravenous patient-controlled analgesia (IV-PCA) at 24 hour postoperatively. The secondary outcomes were the visual analogue scale (VAS) scores at 1, 6, 24, and 48 hour postoperatively and the occurrence of adverse events and patient satisfaction after the surgery. RESULTS: Forty-six patients were included, 24 in group C and 22 in group R. The cumulative morphine consumption using IV-PCA did not differ between the two groups (P = 0.631). The intraoperative use of remifentanil was higher in group C than in group R (P = 0.025). The resting and coughing VAS scores at 1 hour postoperatively were higher in group R than in group C (P = 0.011, P = 0.004). The incidence of adverse events and patient satisfaction was not significantly different between the two groups. CONCLUSIONS: A single injection of ultrasound-guided RLB did not reduce postoperative analgesic requirements following breast surgery.

Concealed congenital long QT syndrome during velopharyngeal dysfunction correction: a case report.

The congenital long QT syndrome (LQTS) is an inherited cardiac disorder characterized by increased QT intervals and a tendency to experience ventricular tachycardia, which can cause fainting, heart failure, or sudden death. A 4-year-old female patient undergoing velopharyngeal correction surgery under general anesthesia suddenly developed Torsades de pointes. Although the patient spontaneously resolved to sinus rhythm without treatment, subsequent QT prolongation persisted. Here, we report a case of concealed LQTS with a literature review.

Effects of Intraoperative Low-Dose Ketamine on Persistent Postsurgical Pain after Breast Cancer Surgery: A Prospective, Randomized, Controlled, Double-Blind Study.

BACKGROUND: Compared to acute postsurgical pain, studies regarding the role of ketamine in persistent postsurgical pain (PPSP) are limited. OBJECTIVES: The aim of this clinical trial was to test if intraoperative low-dose ketamine without postoperative infusion would reduce PPSP development after breast cancer surgery. STUDY DESIGN: We used a randomized, double-blinded, placebo study design. SETTING: This study was conducted at Pusan National University Hospital, Republic of Korea, between December 2013 and August 2016. METHODS: A total of 184 patients scheduled for breast cancer surgery were randomly assigned to either the control or ketamine group. Before skin incision, a bolus (0.5 mg/kg of ketamine or placebo), followed by a continuous infusion (0.12 mg/kg/h of ketamine or placebo), was administered until the end of the surgery. The patients were interviewed via telephone 1, 3, and 6 months after surgery. The first question was whether the patient had surgery-related pain. If answered affirmatively, questions from the Numeric Rating Scale for pain at rest (NRSr) and for coughing (NRSd) were also asked. Our primary outcome was the incidence of PPSP at 3 months after surgery. RESULTS: For PPSP analysis, 168 patients were included. The number of patients who experienced pain was significantly lower in the ketamine group at 3 months (86.9% in the control group vs 69.0% in the ketamine group, P = .005) postoperatively. However, the NRSr and NRSd did not differ between the groups throughout the follow-up. LIMITATIONS: There were no postoperative low-dose ketamine infusion groups to compare due to hospital regulations. Dosage of ketamine was too low to reduce the severity of PPSP. And by using propofol and remifentanil for anesthesia, different results can be deduced with volatile anesthetics. Data from written questionnaires would have been more specific than telephone interviews for long-term assessment. CONCLUSIONS: Though intraoperative low-dose ketamine without postoperative infusion significantly reduced the incidence of PPSP up to 3 months after breast cancer surgery, it failed to reduce clinically significant PPSP and improve patients' quality of life. KEY WORDS: Analgesia, breast cancer, chronic pain, ketamine, mastectomy, morphine, pain, postoperative, propofol.

Insights Into Mucosal Innate Immune Responses in House Dust Mite-Mediated Allergic Asthma.

The prevalence of asthma has been rising steadily for several decades, and continues to be a major public health and global economic burden due to both direct and indirect costs. Asthma is defined as chronic heterogeneous inflammatory diseases characterized by airway obstruction, mucus production and bronchospasm. Different endotypes of asthma are being recognized based on the distinct pathophysiology, genetic predisposition, age, prognosis, and response to remedies. Mucosal innate response to environmental triggers such as pollen, cigarette smoke, fragrances, viral infection, and house dust mite (HDM) are now recognized to play an important role in allergic asthma. HDM are the most pervasive allergens that co-habitat with us, as they are ubiquitous in-house dusts, mattress and bedsheets, and feed on a diet of exfoliated human skin flakes. Dermatophagoides pteronyssinus, is one among several HDM identified up to date. During the last decade, extensive studies have been fundamental in elucidating the interactions between HDM allergens, the host immune systems and airways. Moreover, the paradigm in the field of HDM-mediated allergy has been shifted away from being solely a Th2-geared to a complex response orchestrated via extensive crosstalk between the epithelium, professional antigen presenting cells (APCs) and components of the adaptive immunity. In fact, HDM have several lessons to teach us about their allergenicity, the complex interactions that stimulate innate immunity in initiating and perpetuating the lung inflammation. Herein, we review main allergens of Dermatophagoides pteronyssinus and their interactions with immunological sentinels that promote allergic sensitization and activation of innate immunity, which is critical for the development of the Th2 biased adaptive immunity to HDM allergens and development of allergic asthma.

Mice Deficient in Epithelial or Myeloid Cell Iκκß Have Distinct Colonic Microbiomes and Increased Resistance to Citrobacter rodentium Infection.

The colonic microenvironment, stemming from microbial, immunologic, stromal, and epithelial factors, serves as an important determinant of the host response to enteric pathogenic colonization. Infection with the enteric bacterial pathogen Citrobacter rodentium elicits a strong mucosal Th1-mediated colitis and monocyte-driven inflammation activated via the classical NF-κB pathway. Research has focused on leukocyte-mediated signaling as the main driver for C. rodentium-induced colitis, however we hypothesize that epithelial cell NF-κB also contributes to the exacerbation of infectious colitis. To test this hypothesis, compartmentalized classical NF-κB defective mice, via the deletion of IKKß in either intestinal epithelial cells (IKKßΔIEC) or myeloid-derived cells (IKKßΔMY), and wild type (WT) mice were challenged with C. rodentium. Both pathogen colonization and colonic histopathology were significantly reduced in IKKß-deficient mice compared to WT mice. Interestingly, colonic IL-10, RegIIIγ, TNF-α, and iNOS gene expression were increased in IKKß-deficient mice in the absence of bacterial challenge. This was associated with increased p52, which is involved with activation of NF-κß through the alternative pathway. IKKß-deficient mice also had distinct differences in colonic tissue-associated and luminal microbiome that may confer protection against C. rodentium. Taken together, these data demonstrate that classical NF-κB signaling can lead to enhanced enteric pathogen colonization and resulting colonic histopathology.

Reduced expression of the Ion channel CFTR contributes to airspace enlargement as a consequence of aging and in response to cigarette smoke in mice.

Chronic Obstructive Pulmonary Disease (COPD) is a complex disease resulting in respiratory failure and represents the third leading cause of global death. The two classical phenotypes of COPD are chronic bronchitis and emphysema. Owing to similarities between chronic bronchitis and the autosomal-recessive disease Cystic Fibrosis (CF), a significant body of research addresses the hypothesis that dysfunctional CF Transmembrane Conductance Regulator (CFTR) is implicated in the pathogenesis of COPD. Much less attention has been given to emphysema in this context, despite similarities between the two diseases. These include early-onset cellular senescence, similar comorbidities, and the finding that CF patients develop emphysema as they age. To determine a potential role for CFTR dysfunction in the development of emphysema, Cftr+/+ (Wild-type; WT), Cftr+/- (heterozygous), and Cftr-/- (knock-out; KO) mice were aged or exposed to cigarette smoke and analyzed for airspace enlargement. Aged knockout mice demonstrated increased alveolar size compared to age-matched wild-type and heterozygous mice. Furthermore, both heterozygous and knockout mice developed enlarged alveoli compared to their wild-type counterparts following chronic smoke exposure. Taken into consideration with previous findings that cigarette smoke leads to reduced CFTR function, our findings suggest that decreased CFTR expression sensitizes the lung to the effects of cigarette smoke. These findings may caution normally asymptomatic CF carriers against exposure to cigarette smoke; as well as highlight emphysema as a future challenge for CF patients as they continue to live longer. More broadly, our data, along with clinical findings, may implicate CFTR dysfunction in a pathology resembling accelerated aging.