No more tears from surgical site infections in interventional pain management

As the field of interventional pain management (IPM) grows, the risk of surgical site infections (SSIs) is increasing. SSI is defined as an infection of the incision or organ/space that occurs within one month after operation or three months after implantation. It is also common to find patients with suspected infection in an outpatient clinic. The most frequent IPM procedures are performed in the spine. Even though primary pyogenic spondylodiscitis via hematogenous spread is the most common type among spinal infections, secondary spinal infections from direct inoculation should be monitored after IPM procedures. Various preventive guidelines for SSI have been published. Cefazolin, followed by vancomycin, is the most commonly used surgical antibiotic prophylaxis in IPM. Diagnosis of SSI is confirmed by purulent discharge, isolation of causative organisms, pain/tenderness, swelling, redness, or heat, or diagnosis by a surgeon or attending physician. Inflammatory markers include traditional (C-reactive protein, erythrocyte sedimentation rate, and white blood cell count) and novel (procalcitonin, serum amyloid A, and presepsin) markers. Empirical antibiotic therapy is defined as the initial administration of antibiotics within at least 24 hours prior to the results of blood culture and antibiotic susceptibility testing. Definitive antibiotic therapy is initiated based on the above culture and testing. Combination antibiotic therapy for multidrug-resistant Gramnegative bacteria infections appears to be superior to monotherapy in mortality with the risk of increasing antibiotic resistance rates. The never-ending war between bacterial resistance and new antibiotics is continuing. This article reviews prevention, diagnosis, and treatment of infection in pain medicine.

Pyogenic Andersson Lesion in a Patient With Ankylosing Spondylitis / 대한신경손상학회지

Although the exact etiology of the Andersson lesion (AL) remains unclear, it is known to occur mostly in patients with long-standing ankylosing spondylitis (AS). Among the various theories for the etiology of AL, repetitive trauma and inflammatory causes are the most common. The histopathological appearance of the AL in this report was consistent with that of chronic inflammation without any infection. Pyogenic ALs in the context of AS are extremely rare; to the best of our knowledge, positive cultures of this lesion in bone biopsies have never been reported. Herein, we report a rare case of a pyogenic AL with a positive culture and discuss a relevant review of the literature.

Neurological Deterioration Immediately After Lumbar Surgery: Anesthetic Consideration for Co-existing Cervical Lesion: A Case Report / 대한신경손상학회지

Most spine surgeons and anesthesiologists believe that the risk of spinal cord injury (SCI) during intubation is mainly due to mechanical compression of the spinal cord due to cervical spine movement in cases of undiagnosed but severe cervical lesions. With this reasoning, difficult intubation, which is more frequently encountered in patients with preexisting cervical diseases, is likely to result in SCI. Several reports have described SCI after non-cervical surgery in patients previously diagnosed with cervical myelopathy and a chronically compressed cervical cord; however, to date, there is less acknowledgement of SCI in patients with undiagnosed cervical myelopathy. Here, we report a painful experience of neurological deterioration that developed immediately after elective lumbar decompressive surgery in a 76-year-old man. The possible mechanism behind these unexpected complications is discussed in a review of the literature.

The Clinical Outcome of Extraskeletal Myxoid Chondrosarcoma / 대한정형외과학회잡지

Purpose@#Extraskeletal myxoid chondrosarcoma (EMC) is an extremely rare malignant mesenchymal neoplasm, accounting for less than 3% of soft tissue sarcomas. This sarcoma is usually characterized by its indolent course. This study examined the clinical manifestations and oncologic outcomes of EMC. @*Materials and Methods@#Seventeen patients diagnosed and treated for EMC between January 2008 and December 2018 were enrolled in this study. The cohort was then reviewed regarding age, gender, symptom onset, tumor location, magnetic resonance images, surgical margin, and pathologic diagnosis. The time to local recurrence and metastasis, follow-up duration, and the patients’ final status were analyzed. @*Results@#The patients were comprised of 10 males and seven female patients with a mean age of 54 (range, 31–79). The tumor location was the buttock in five, thigh in four, knee in three, foot in three, shoulder in one, and back in one. The average tumor diameter was 11.5 cm (range, 2.2–23.2 cm). At the time of diagnosis, five patients were American Joint Committee on Cancer stage II; three were IIIA; three were IIIB; six were IV. Local recurrence occurred in 12 cases, and distant metastasis occurred in 15 cases. The five-year overall survival of the patients with EMC was 73%±17%, and two patients died of the disease. @*Conclusion@#Despite the high rate of local recurrence and distant metastasis, the long-term survival rate in patients with EMC is quite high because of its indolent characteristics.

Prognostic Value of Estimated Plasma Volume Status in Patients With Sepsis

Background@#In patients with sepsis, timely risk stratification is important to improve prognosis. Although several clinical scoring systems are currently being used to predict the outcome of sepsis, but they all have certain limitations. The objective of this study was to evaluate the prognostic value of estimated plasma volume status (ePVS) in patients admitted to the intensive care unit (ICU) with sepsis or septic shock. @*Methods@#This single-center, prospective observational study, included 100 patients admitted to the ICU with sepsis or septic shock. Informed consent, blood samples, and co-morbidity data were obtained from the patients on admission, and the severity of sepsis was recorded.The primary outcome was in-hospital mortality and multivariable logistic regression analysis was used to adjust for confounding factors to determine the significant prognostic factor. @*Results@#The in-hospital mortality was 47%. The ePVS was correlated with the amount of total fluids administered 24 hours before the ICU admission. The mean ePVS in patients who died was higher than in those who survived (7.7 ± 2.1 dL/g vs. 6.6 ± 1.6 dL/g, P = 0.003). To evaluate the utility of ePVS in predicting in-hospital mortality, a receiver operating characteristic curve was produced. Sensitivity and specificity were optimal at a cut-off point of 7.09 dL/g, with an area under the curve of 0.655. In the multivariate analysis, higher ePVS was significantly associated with higher in-hospital mortality adjusted odds ratio, 1.39; 95% confidence interval, 1.04–1.85, P = 0.028). The Kaplan-Meier curve showed that an ePVS value above 7.09 was associated with an increased risk of in-hospital mortality compared with the rest of the population (P = 0.004). @*Conclusion@#The ePVS was correlated with the amount of intravenous fluid resuscitation and may be used as a simple and novel prognostic factor in patients with sepsis or septic shock who are admitted to the ICU.

Percutaneous osteoplasty for painful bony lesions: a technical survey

Percutaneous osteoplasty (POP) is defined as the injection of bone cement into various painful bony lesions, refractory to conventional therapy, as an extended technique of percutaneous vertebroplasty (PVP). POP can be applied to benign osteochondral lesions and malignant metastatic lesions throughout the whole skeleton, whereas PVP is restricted to the vertebral body. Common spinal metastases occur in the thoracic (70%), lumbosacral (20%), and cervical (10%) vertebrae, in order of frequency. Extraspinal metastases into the ribs, scapulae, sternum, and humeral head commonly originate from lung and breast cancers; extraspinal metastases into the pelvis and femoral head come from prostate, urinary bladder, colon, and uterine cervical cancers. Pain is aggravated in the dependent (or weight bearing) position, or during movement (or respiration). The tenderness and imaging diagnosis should match. The supposed mechanism of pain relief in POP is the augmentation of damaged bones, thermal and chemical ablation of the nociceptive nerves, and local inhibition of tumor invasion. Adjacent (facet) joint injections may be needed prior to POP (PVP). The length and thickness of the applied needle should be chosen according to the targeted bone. Bone cement is also selected by its osteoconduction, osteoinduction, and osteogenesis. Needle route should be chosen as a shortcut to reach the target bony lesions, without damage to the nerves and vessels. POP is a promising minimally invasive procedure for immediate pain relief. This review provides a technical survey for POPs in painful bony lesions.

Mirogabalin: could it be the next generation gabapentin or pregabalin?

Except for carbamazepine for trigeminal neuralgia, gabapentinoid anticonvulsants have been the standard for the treatment of neuropathic pain. Pregabalin, which followed gabapentin, was developed with the benefit of rapid peak blood concentration and better bioavailability. Mirogabalin besylate (DS-5565, Tarlige® ) shows greater sustained analgesia due to a high affinity to, and slow dissociation from, the α2 δ-1 subunits in the dorsal root ganglion (DRG). Additionally, it produces a lower level of central nervous system-specific adverse drug reactions (ADRs), due to a low affinity to, and rapid dissociation from, the α2 δ-2 subunits in the cerebellum. Maximum plasma concentration is achieved in less than 1 hour, compared to 1 hour for pregabalin and 3 hours for gabapentin. The plasma protein binding is relatively low, at less than 25%. As with all gabapentinoids, it is also largely excreted via the kidneys in an unchanged form, and so the administration dose should also be adjusted according to renal function. The equianalgesic daily dose for 30 mg of mirogabalin is 600 mg of pregabalin and over 1,200 mg of gabapentin. The initial adult dose starts at 5 mg, given orally twice a day, and is gradually increased by 5 mg at an interval of at least a week, to 15 mg. In conclusion, mirogabalin is anticipated to be a novel, safe gabapentinoid anticonvulsant with a greater therapeutic effect for neuropathic pain in the DRG and lower ADRs in the cerebellum.

Percutaneous osteoplasty for painful bony lesions: a technical survey

Percutaneous osteoplasty (POP) is defined as the injection of bone cement into various painful bony lesions, refractory to conventional therapy, as an extended technique of percutaneous vertebroplasty (PVP). POP can be applied to benign osteochondral lesions and malignant metastatic lesions throughout the whole skeleton, whereas PVP is restricted to the vertebral body. Common spinal metastases occur in the thoracic (70%), lumbosacral (20%), and cervical (10%) vertebrae, in order of frequency. Extraspinal metastases into the ribs, scapulae, sternum, and humeral head commonly originate from lung and breast cancers; extraspinal metastases into the pelvis and femoral head come from prostate, urinary bladder, colon, and uterine cervical cancers. Pain is aggravated in the dependent (or weight bearing) position, or during movement (or respiration). The tenderness and imaging diagnosis should match. The supposed mechanism of pain relief in POP is the augmentation of damaged bones, thermal and chemical ablation of the nociceptive nerves, and local inhibition of tumor invasion. Adjacent (facet) joint injections may be needed prior to POP (PVP). The length and thickness of the applied needle should be chosen according to the targeted bone. Bone cement is also selected by its osteoconduction, osteoinduction, and osteogenesis. Needle route should be chosen as a shortcut to reach the target bony lesions, without damage to the nerves and vessels. POP is a promising minimally invasive procedure for immediate pain relief. This review provides a technical survey for POPs in painful bony lesions.

Mirogabalin: could it be the next generation gabapentin or pregabalin?

Except for carbamazepine for trigeminal neuralgia, gabapentinoid anticonvulsants have been the standard for the treatment of neuropathic pain. Pregabalin, which followed gabapentin, was developed with the benefit of rapid peak blood concentration and better bioavailability. Mirogabalin besylate (DS-5565, Tarlige® ) shows greater sustained analgesia due to a high affinity to, and slow dissociation from, the α2 δ-1 subunits in the dorsal root ganglion (DRG). Additionally, it produces a lower level of central nervous system-specific adverse drug reactions (ADRs), due to a low affinity to, and rapid dissociation from, the α2 δ-2 subunits in the cerebellum. Maximum plasma concentration is achieved in less than 1 hour, compared to 1 hour for pregabalin and 3 hours for gabapentin. The plasma protein binding is relatively low, at less than 25%. As with all gabapentinoids, it is also largely excreted via the kidneys in an unchanged form, and so the administration dose should also be adjusted according to renal function. The equianalgesic daily dose for 30 mg of mirogabalin is 600 mg of pregabalin and over 1,200 mg of gabapentin. The initial adult dose starts at 5 mg, given orally twice a day, and is gradually increased by 5 mg at an interval of at least a week, to 15 mg. In conclusion, mirogabalin is anticipated to be a novel, safe gabapentinoid anticonvulsant with a greater therapeutic effect for neuropathic pain in the DRG and lower ADRs in the cerebellum.

All about pain pharmacology: what pain physicians should know

From the perspective of the definition of pain, pain can be divided into emotional and sensory components, which originate from potential and actual tissue damage, respectively. The pharmacologic treatment of the emotional pain component includes antianxiety drugs, antidepressants, and antipsychotics. The anti-anxiety drugs have anti-anxious, sedative, and somnolent effects. The antipsychotics are effective in patients with positive symptoms of psychosis. On the other hand, the sensory pain component can be divided into nociceptive and neuropathic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are usually applied for somatic and visceral nociceptive pain, respectively; anticonvulsants and antidepressants are administered for the treatment of neuropathic pain with positive and negative symptoms, respectively. The NSAIDs, which inhibit the cyclo-oxygenase pathway, exhibit anti-inflammatory, antipyretic, and analgesic effects; however, they have a therapeutic ceiling. The adverse reactions (ADRs) of the NSAIDs include gastrointestinal problems, generalized edema, and increased bleeding tendency. The opioids, which bind to the opioid receptors, present an analgesic effect only, without anti-inflammatory, antipyretic, or ceiling effects. The ADRs of the opioids start from itching and nausea/vomiting to cardiovascular and respiratory depression, as well as constipation. The anticonvulsants include carbamazepine, related to sodium channel blockade, and gabapentin and pregabalin, related to calcium blockade. The antidepressants show their analgesic actions mainly through inhibiting the reuptake of serotonin or norepinephrine. Most drugs, except NSAIDs, need an updose titration period. The principle of polypharmacy for analgesia in case of mixed components of pain is increasing therapeutic effects while reducing ADRs, based on the origin of the pain.

Factors for Survival and Complications of Malignant Bone Tumor Patients with a Total Femoral Replacement / 대한정형외과학회잡지

Purpose@#Total femoral replacement (TFR) is an extreme form of limb salvage. Considering the rarity of this procedure, reports have focused on the complications and a proper indication is unclear. This study analyzed 36 patients with TFR who were asked the following: 1) prognostic factors related to survival in patients who underwent TFR with a tumoral cause; 2) overall implant and limb survival; 3) complications, functional outcome, and limb status for patients surviving for more than 3 years. @*Materials and Methods@#According to the causes for TFR, 36 patients were categorized into three groups: extensive primary tumoral involvement (group 1, 15 cases), tumoral contamination by an inadvertent procedure or local recurrence (group 2, 16 cases), and salvage of a failed reconstruction (group 3, 5 cases). The factors that may affect the survival of patients included age, sex, cause of TFR, and tumor volume change after chemotherapy. @*Results@#The overall five-year survival of the 36 patients was 31.5%±16.2%. The five-year survival of 31 patients with tumoral causes was 21.1%±15.6%. The five-year survival of 50.0%±31.0% in patients with a decreased tumor volume after chemotherapy was higher than that of increased tumor volume (p=0.02). The five-year survival of 12 cases with a wide margin was 41.7%±27.9%, whereas that of the marginal margin was 0.0%±0.0% (p=0.03). The ten-year overall implant survival of 36 patients was 85.9%±14.1%. The five-year revisionfree survival was 16.6%±18.2%. At the final follow-up, 12 maintained tumor prosthesis, three underwent amputation (rotationplasty, 2; above knee amputation, 1), and the remaining one had knee fusion. Among 16 patients with a follow-up of more than three years, 14 patients underwent surgical intervention and two patients had conservative management. Complications included infection in 10 cases, local recurrences in two cases, and one case each of hip dislocation, bushing fracture, and femoral artery occlusion. @*Conclusion@#Patients showing an increased tumor volume after chemotherapy and having an inadequate surgical margin showed a high chance of early death. In the long-term follow-up, TFR showed a high infection rate and the functional outcome was unsatisfactory. Nevertheless, this procedure is an inevitable option of limb preservation in selected patients.

Stem cell therapy in pain medicine / 대한통증학회지

Stem cells are attracting attention as a key element in future medicine, satisfying the desire to live a healthier life with the possibility that they can regenerate tissue damaged or degenerated by disease or aging. Stem cells are defined as undifferentiated cells that have the ability to replicate and differentiate themselves into various tissues cells. Stem cells, commonly encountered in clinical or preclinical stages, are largely classified into embryonic, adult, and induced pluripotent stem cells. Recently, stem cell transplantation has been frequently applied to the treatment of pain as an alternative or promising approach for the treatment of severe osteoarthritis, neuropathic pain, and intractable musculoskeletal pain which do not respond to conventional medicine. The main idea of applying stem cells to neuropathic pain is based on the ability of stem cells to release neurotrophic factors, along with providing a cellular source for replacing the injured neural cells, making them ideal candidates for modulating and possibly reversing intractable neuropathic pain. Even though various differentiation capacities of stem cells are reported, there is not enough knowledge and technique to control the differentiation into desired tissues in vivo. Even though the use of stem cells is still in the very early stages of clinical use and raises complicated ethical problems, the future of stem cells therapies is very bright with the help of accumulating evidence and technology.

Antipsychotics for patients with pain

Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (α), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak D₂ receptor bindings with strong binding to the 5-HT(2A) receptor, while typical antipsychotics block long-lasting, tight D₂ receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.

Successful removal of permanent spinal cord stimulators in patients with complex regional pain syndrome after complete relief of pain

BACKGROUND: It is uncommon for patients who have received a permanent implant to remove the spinal cord stimulator (SCS) after discontinuation of medication in complex regional pain syndrome (CRPS) due to their completely painless state. This study evaluated CRPS patients who successfully removed their SCSs. METHODS: This 10-year retrospective study was performed on patients who had received the permanent implantation of an SCS and had removed it 6 months after discontinuation of stimulation, while halting all medications for neuropathic pain. Age, sex, duration of implantation, site and type of CRPS, and their return to work were compared between the removal and non-removal groups. RESULTS: Five (12.5%, M/F = 4/1) of 40 patients (M/F = 33/7) successfully removed the permanent implant. The mean age was younger in the removal group (27.2 ± 6.4 vs. 43.5 ± 10.7 years, P < 0.01). The mean duration of implantation in the removal group was 34.4 ± 18.2 months. Two of 15 patients (13.3%) and 3 of 25 patients (12%) who had upper and lower extremity pain, respectively, had removed the implant. The implants could be removed in 5 of 27 patients (18.5%) with CRPS type 1 (P < 0.01). All 5 patients (100%) who removed their SCS returned to work, while only 5 of 35 (14.3%) in the non-removal group did (P < 0.01). CONCLUSIONS: Even though this study had limited data, younger patients with CRPS type 1 could remove their SCSs within a 5-year period and return to work with complete pain relief.

Propofol promotes osteoclastic bone resorption by increasing DC-STAMP expression

BACKGROUND: Propofol is an intravenous anesthetic which has antioxidant effects due to its similarity in molecular structure to α-tocopherol. It has been reported that α-tocopherol increases osteoclast fusion and bone resorption. Here, we investigated the effects of propofol on signaling pathways of osteoclastogenic gene expression, as well as osteoclastogenesis and bone resorption using bone marrow-derived macrophages (BMMs). METHODS: BMMs were cultured with macrophage colony-stimulating factor (M-CSF) alone or M-CSF plus receptor activator of nuclear factor kappa B ligand (RANKL) in the presence of propofol (0–50 µM) for 4 days. Mature osteoclasts were stained for tartrate-resistant acid phosphatase (TRAP) and the numbers of TRAP-positive multinucleated osteoclasts were counted. To examine the resorption activities of osteoclasts, a bone resorption assay was performed. To identify the mechanism of action of propofol on the formation of multinucleated osteoclasts, we focused on dendritic cell-specific transmembrane protein (DC-STAMP), a protein essential for pre-osteoclastic cell fusion. RESULTS: Propofol increased the formation of TRAP-positive multinucleated osteoclasts. In addition, the bone resorption assay revealed that propofol increased the bone resorption area on dentin discs. The mRNA expression of DC-STAMP was upregulated most strongly in the presence of both RANKL and propofol. However, SB203580, a p38 inhibitor, significantly suppressed the propofol/RANKL-induced increase in mRNA expression of DC-STAMP. CONCLUSION: We have demonstrated that propofol enhances osteoclast differentiation and maturation, and subsequently increases bone resorption. Additionally, we identified the regulatory pathway underlying osteoclast cell-cell fusion, which was enhanced by propofol through p38-mediated DC-STAMP expression.

Diagnostic value of serum IgM enzyme-linked immunosorbent assays in polymerase chain reaction-positive Mycoplasma pneumonia in children

PURPOSE: Mycoplasma pneumoniae (MP) is a common cause of community-acquired pneumonia (CAP) in children. MP serum IgM and polymerase chain reaction (PCR) are the methods that enable early diagnosis in patients with MP pneumonia. The objective of this study was to investigate the clinical value of serum MP-specific IgM antibodies in PCR-positive MP pneumonia for the early diagnosis of MP pneumonia in children with CAP. METHODS: Out of 129 patients with lower respiratory tract infection aged over 3 years, 90 CAP children were enrolled in the study. Throat swab MP real-time PCR and serum enzyme-linked immunosorbent assays (ELISA) IgM antibodies were performed. A positive rate of MP PCR and serum IgM, the level of IgM index, clinical features, and laboratory findings were analyzed. RESULTS: PCR was positive in 57 cases. Longer fever duration before admission (P < 0.001), higher rates of lobar or segmental pneumonia (P=0.048), unilateral infiltration (P=0.038), and extrapulmonary symptoms (P=0.049) were associated with MP PCR-positive pneumonia. Serum IgM index was significantly higher in MP PCR-positive pneumonia them in MP PCR-negative pneumonia (3.9±3.0 vs. 0.8±1.3, P < 0.001). Using MP PCR as a gold standard, the sensitivity, specificity, positive predictive value and negative predictive value of serum IgM were 85.5%, 82.1%, 91.4%, and 71.9%, respectively. The area under the curves for serum IgM index was 0.892, and the ROC analysis indicated that an optimal cutoff value of 1.05 for serum IgM provided the highest sensitivity and specificity interestingly (83.9% vs. 85.7%, P < 0.001). CONCLUSION: Serum IgM ELISA has useful diagnostic value in PCR-positive MP pneumonia. Applying an IgM index cutoff of 1.05 improves diagnostic accuracy.

Extraspinal Percutaneous Osteoplasty for the Treatment of Painful Bony Metastasis

BACKGROUND: Extraspinal percutaneous osteoplasties (POPs) are novel techniques for the treatment of painful bony metastasis, which is often the cause of both persistent and incidental breakthrough pain. This retrospective study explored the efficacy and complications of extraspinal POPs. METHODS: The origin of the cancer metastasis, performed POP sites, necessity of adjacent joint injections, pain and Karnofsky Performance Scale (KPS) scores, complications related to the POPs, and life expectancy were evaluated from the medical records from 2009 to 2016. RESULTS: A total of 47 (M/F = 28/19) patients had received 54 POPs, including costoplasty, scapuloplasty, ilioplasty, humeroplasty, ischioplasty, femoroplasty, sternoplasty, and puboplasty, in order of frequency. The most common sites for the origin of the cancer, in order of frequency, were the lung, liver, breast, colon, and kidney. All patients receiving POPs including scapuloplasty, ilioplasty, humeroplasty, and femoroplasty needed adjacent joint injections before or after the POPs. Pain due to metastatic lesions was reduced significantly immediately after the POPs and the reduction was sustained until the end of their lives. The median KPS was increased from 35.4% to 67.7% immediately after the POPs. There were no complications related to the procedures. The mean life expectancy after performing the POPs, for 35 patients which died afterwards, was 99.3 days, ranging from 1 to 767 days. CONCLUSION: Even though pain in the isolated POP sites may be difficult to measure due to overlapping systemic pain, the POPs provided immediate local pain relief, and the patients showed better physical performance without procedure-related complications.

Can oliceridine (TRV130), an ideal novel µ receptor G protein pathway selective (µ-GPS) modulator, provide analgesia without opioid-related adverse reactions?

All drugs have both favorable therapeutic and untoward adverse effects. Conventional opioid analgesics possess both analgesia and adverse reactions, such as nausea, vomiting, and respiratory depression. The opioid ligand binds to µ opioid receptor and non-selectively activates two intracellular signaling pathways: the G protein pathway induce analgesia, while the β-arrestin pathway is responsible for the opioid-related adverse reactions. An ideal opioid should activate the G protein pathway while deactivating the β-arrestin pathway. Oliceridine (TRV130) has a novel characteristic mechanism on the action of the µ receptor G protein pathway selective (µ-GPS) modulation. Even though adverse reactions (ADRs) are significantly attenuated, while the analgesic effect is augmented, the some residual ADRs persist. Consequently, a G protein biased µ opioid ligand, oliceridine, improves the therapeutic index owing to increased analgesia with decreased adverse events. This review article provides a brief history, mechanism of action, pharmacokinetics, pharmacodynamics, and ADRs of oliceridine.

The association between nasal eosinophilia and aeroallergen sensitization in children and adolescents with rhinitis

PURPOSE: To identify the correlation between nasal eosinophilia and aeroallergen sensitization in children and adolescents. METHODS: This is a retrospective study of patients below 18 years of age who had a history of rhinitis that lasted more than 2 weeks or had been repeated more than once a year, received nasal eosinophil examinations, and had serum specific IgE to aeroallergens measured at an Allergy Clinic in a single tertiary teaching hospital in Seoul, Korea. The percentage of nasal eosinophils was calculated by the number of eosinophils per total leukocytes in a high-power field of 1,000×. Data was analyzed to determine the association between nasal eosinophilia and 18 aeroallergens. RESULTS: Of the 245 patients included, 156 (63.7%) were male and the mean age (±standard deviation) was 7.9 years (±3.8). In total, 175 patients (71.4%) were sensitized to at least 1 of the 18 aeroallergens tested, and sensitization to house dust mite was most common. In addition, 118 (48.2%) and 69 patients (28.2%) had nasal eosinophilia of at least 1% and 5%, respectively. There were no significant correlations between serum total IgE or age and the percentage of nasal eosinophils. However, the percentage of nasal eosinophils in the group sensitized to any aeroallergens was significantly increased compared to the nonsensitized group (P=0.002). The percentage of nasal eosinophils was significantly higher in patients who were sensitized to Birch-Alder Mix, oak white, Bermuda grass, orchard grass, timothy grass, sweet vernal grass, rye, mugwort, short ragweed, Alternaria alternata, cats, dogs or Dermatophagoides farinae compared to those nonsensitized. CONCLUSION: Nasal eosinophilia was significantly associated with sensitization to aeroallergens.

TRPV1 Blocking Alleviates Airway Inflammation and Remodeling in a Chronic Asthma Murine Model

PURPOSE: Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. There is emerging interest in the involvement of the transient receptor potential vanilloid 1 (TRPV1) channel in the pathophysiology of asthma. This study examined whether TRPV1 antagonism alleviates asthma features in a murine model of chronic asthma. METHODS: BALB/c mice were sensitized to and challenged by ovalbumin to develop chronic asthma. Capsazepine (TRPV1 antagonist) or TRPV1 small interfering RNA (siRNA) was administered in the treatment group to evaluate the effect of TPV1 antagonism on AHR, airway inflammation, and remodeling. RESULTS: The mice displayed increased AHR, airway inflammation, and remodeling. Treatment with capsazepine or TRPV1 siRNA reduced AHR to methacholine and airway inflammation. Type 2 T helper (Th2) cytokines (interleukin [IL]-4, IL-5, and IL-13) were reduced and epithelial cell-derived cytokines (thymic stromal lymphopoietin [TSLP], IL-33, and IL-25), which regulate Th2 cytokine-associated inflammation, were also reduced. Airway remodeling characterized by goblet cell hyperplasia, increased α-smooth muscle action, and collagen deposition was also alleviated by both treatments. CONCLUSIONS: Treatment directed at TRPV1 significantly alleviated AHR, airway inflammation, and remodeling in a chronic asthma murine model. The TRPV1 receptor can be a potential drug target for chronic bronchial asthma.