COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated type 1 interferon (IFN-1) production, the pathophysiology of which involves sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) tetramerization and the cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. As a result, type I interferonopathies are exacerbated. Aspirin inhibits cGAS-mediated signaling through cGAS acetylation. Acetylation contributes to cGAS activity control and activates IFN-1 production and nuclear factor-κB (NF-κB) signaling via STING. Aspirin and dapsone inhibit the activation of both IFN-1 and NF-κB by targeting cGAS. We define these as anticatalytic mechanisms. It is necessary to alleviate the pathologic course and take the lag time of the odds of achieving viral clearance by day 7 to coordinate innate or adaptive immune cell reactions.

The Optimal Approach for a Superior Hypogastric Plexus Block.

INTRODUCTION: Superior hypogastric plexus block (SHGPB) is technically difficult, and an accurate procedure is required to avoid potential complications. We attempted to determine the reference angles for fluoroscopy-assisted SHGPB and to establish a predictor as a guide to select the optimal approach between the classic posterior approach and transdiscal approach. METHODS: Abdominopelvic computed tomography (CT) scans from 268 patients diagnosed with pelvic malignancies were examined. The oblique and axial angles needed for the fluoroscope were measured both for posterior and transdiscal approaches by simulating the needle trajectory on CT imaging. We developed an SHGPB index defined by the ratio (%) of the interposterior iliac border distance to the L5 body transverse diameter, which represents the relative transverse diameter of the bony pelvis. We evaluated whether it can help select the optimal approach for the SHGPB between the posterior and transdiscal approaches. RESULTS: Males had a significantly smaller angle than females (right oblique angle for posterior approach, males 14 [range 12 to 17] degrees vs. females 19 [range 16 to 23] degrees; P < 0.001). An SHGPB index of < 150 was an independent predictor for failure of the classic posterior approach (odds ratio 31.3, 95% confidence interval 5.1 to 104.7). CONCLUSIONS: The optimal right oblique angle of fluoroscopy for the posterior approach is 13° to 15° in males and 19° to 20° in females. The transdiscal approach may be favored over the posterior approach when the bony pelvis is narrow relative to the target vertebral body, which can be measured by the SHGPB index being < 150.

The influence of patient position on withdrawal force of lumbar epidural catheters after total knee arthroplasty: A randomized trial.

STUDY OBJECTIVE: Elderly patients with degenerative knee disease may have accompanying degenerative spine conditions. There are no studies on lumbar epidural catheter withdrawal forces in these patients. The aim of this study was to investigate withdrawal forces and possible associated risk factors in patients undergoing total knee arthroplasty (TKA). DESIGN: Prospective randomized trial. SETTING: Operating room and ward in a university hospital. PATIENTS: Seventy-eight patients aged 65 to 80years who were undergoing TKA and combined spinal epidural anesthesia were enrolled. INTERVENTIONS: Lumbar epidural catheterization was performed in a lateral position before surgery and the patients were randomly allocated to one of 3 positions for removal: flexed lateral (L), prone (P), and sitting (S). On the third postoperative day, the lumbar epidural catheters were removed by a single investigator with the patient in the assigned position. MEASUREMENTS: We measured the peak tension during catheter withdrawal and evaluated the factors affecting peak tension. MAIN RESULTS: The forces required to remove the catheters were considerably greater in the sitting and prone than in the flexed lateral position: group P (3.9N [0.28-10.36]), group S (4.1N [0.04-11.57]), and group L (1.3N [0.07-3.65]) (P<.001). There was a positive correlation between the length of catheter in the epidural space and peak tension (P=.0026, ß coefficient=.223). CONCLUSIONS: For ease of removal of catheters from the lumbar epidural space, the flexed lateral position is recommended for elderly patients undergoing TKA. When placing the epidural catheter, the physician should be careful not to insert a catheter that is excessively long.

Insufficient Penetration of Bone Cement Into the Trabecular Bone: A Potential Risk for Delayed Bone Cement Displacement After Kyphoplasty?

OBJECTIVE: Balloon kyphoplasty is a minimally invasive procedure used in the treatment of vertebral compression fractures. Although cement leakage is a well-known complication of the procedure, delayed displacement of the injected bone cement material, occurring several weeks after kyphoplasty, is a rare occurrence. In this report, we describe a case of delayed dislodgement of the bone cement occurring 4 weeks after successful kyphoplasty for an osteoporotic compression fracture of L4. CASE REPORT: A balloon kyphoplasty was successfully performed for the clinical management of an osteoporotic compression fracture of the L4 vertebral body in a 74-year-old patient with Kummel disease. However, further progression of the collapse of L4 vertebra was identified on radiographic imaging obtained 4 weeks after the kyphoplasty. A cystic filling pattern of the bone cement was observed, rather than the expected matrix-like pattern, which contributed to the continued progression of the collapse of the vertebral body. CONCLUSIONS: As delayed displacement of bone cement can result in progression of an osteoporotic compression fracture of the vertebrae, we propose that sufficient penetration of bone cement into the microstructure of the trabecular bone of the vertebral body during kyphoplasty could reduce the risk of this phenomenon.

Effects of two different doses of epidural steroid on blood glucose levels and pain control in patients with diabetes mellitus.

BACKGROUND: A high incidence of diabetes mellitus has been reported among patients diagnosed with lumbar degenerative spinal diseases. Although epidural steroid injections are known to increase the postprocedure blood glucose level, it has not been investigated whether a lower steroid dose can reduce blood glucose excursions and still be effective in controlling patients' subjective pain. OBJECTIVE: We compared the effects of 2 common doses of triamcinolone administered via epidural steroid injections on blood glucose levels and pain control in patients with diabetes mellitus to determine an adequate epidural steroid dose. STUDY DESIGN: A prospective observational study. METHODS: One hundred patients with diabetes mellitus were enrolled. They received lumbar transforaminal, lumbar interlaminar, or caudal epidural triamcinolone for radiculopathy, spinal stenosis, or failed back surgery syndrome. After the type of procedure was clinically determined, the doses of triamcinolone given were randomly chosen, either 40 mg (Group 40) or 20 mg (Group 20). The patients were asked to measure their finger stick blood glucose level twice daily (fasting and postprandial) for 3 days before the injection, on the day of the injection, for 7 days after the injection, and at 14 days after the injection. They also kept a blood glucose diary. Employment status and clinical outcome were evaluated at 8 weeks after the procedure. RESULTS: There were significant increases in fasting blood glucose (FBG) level on postprocedure day (PPD) #1 to PPD #3 in Group 40, but on PPD #1 in Group 20. Moreover, there was a significant difference in FBG between groups on PPD #1 and PPD #2 (FBG on PPD #1: 179 [51]) mg/dL in Group 40 versus 146 [50] mg/dL in Group 20, P < 0.001]. Postprandial blood glucose (PBG) level was significantly elevated in both groups from PPD #0 to PPD #3. Notably, the increase in PBG was significantly greater in Group 40 than Group 20 on PPD #0 and #1 (PBG on PPD #0: 288 [57] mg/dL versus 242 [94] mg/dL in Groups 40 and 20, respectively, P = 0.004). The numeric rating scale for pain reported by the patients decreased for 2 weeks after treatment with no difference between groups. Employment status and clinical outcome was not different between groups. LIMITATIONS: The patients who chose to participate in this study may be a cohort of well-controlled patients with diabetes mellitus. The type of procedure performed was determined by a clinical decision and not randomized. The different routes of administration and diagnosis of failed back surgery syndrome can result in different levels of systemic absorption, thereby influencing the degree and duration of hyperglycemia. In patients with FBSS, the epidural space may be destructed by surgery and adhesive changes in epidural space could be extensive. Therefore, we thought that the absorption of epidural space in these patients would be incomplete or slow compared with those without FBSS. CONCLUSION: Epidural steroid injections were associated with statistically significant elevations in PBG in patients with diabetes for up to 4 days after the procedure. The higher dose of triamcinolone increased FBG and PBG greater than a lower dose did without affecting pain control, employment status, or clinical outcome. Thus, with respect to glucose and pain control, 20 mg of triamcinolone appears to be recommended rather than 40 mg in patients with diabetes. Clinical Trials registration : NCT01435707.

Radiofrequency thermocoagulation of the thoracic splanchnic nerve in functional abdominal pain syndrome -A case report-.

The thoracic splanchnic nerve block has been used in managing abdominal pain, especially for pains arising from abdominal cancers. A 27-year-old male patient who had a constant abdominal pain was referred to our clinic for pain management but had no organic disease. The numeric rating scale (NRS) for pain scored 7/10. We applied a diagnostic thoracic splanchnic nerve block under the diagnosis of functional abdominal pain syndrome. Since the block reduced the pain, we applied a radiofrequency thermocoagulation at the T11 and T12 vertebral level. Thereafter, his symptoms improved markedly with pain decreasing to an NRS score of 2-3/10. Hereby, we report a successful management of functional abdominal pain via radiofrequency thermocoagulation of the thoracic splanchnic nerves.

Preemptive low-dose epidural ketamine for preventing chronic postthoracotomy pain: a prospective, double-blinded, randomized, clinical trial.

OBJECTIVES: Chronic postthoracotomy pain is the most common long-term complication that occurs after a thoracotomy with a reported incidence of up to 80%. Although thoracic epidural analgesia is a widely used method for managing acute postthoracotomy pain, its effects seems questionable. The objective of this prospective, double-blinded, randomized, controlled trial was to assess the effect of preemptive low-dose epidural ketamine in addition to preemptive thoracic epidural analgesia on the incidence of chronic postthoracotomy pain. METHODS: We analyzed 133 patients who were randomized to preemptive thoracic epidural analgesia either with or without ketamine (Group K: 0.12% levobupivacaine, 2 µg/mL of fentanyl, 0.2 mg/mL ketamine, total volume of 500 mL vs. Group KF: 0.12% levobupivacaine, 2 µg/mL of fentanyl, total volume of 500 mL). Pain at the thoracotomy scar site during rest and movement (coughing) was assessed at 2 weeks and 3 months after surgery using a visual analog scale. The incidence of allodynia and numbness was also evaluated. RESULTS: There was no difference in the incidence of chronic postthoracotomy pain at 3 months between the 2 groups (67.7% in group K vs. 75% in group KF). The incidences of allodynia or numbness were not different between the 2 groups. DISCUSSION: The addition of preemptive low-dose epidural ketamine (1.2 mg/h) to preemptive thoracic epidural analgesia did not have any beneficial effects in preventing chronic postthoracotomy pain.

Novel Use of Hydromorphone as a Pretreatment Agent: A Double-blind, Randomized, Controlled Study in Adult Korean Surgical Patients.

BACKGROUND: Hydromorphone is a potent µ-opioid selective agonist that has an onset time within 5 minutes and reaches peak effect between 10 and 20 minutes. However, it may show immediate analgesic effect to rocuronium-induced pain because of its peripheral analgesic property and also may attenuate noxious stimuli from tracheal intubation during induction. The opioid receptors are known to be present in peripheral sensory nerve terminals as well as in the dorsal root ganglion and the central terminal of primary afferent nerves. Therefore, we hypothesized that hydromorphone may be considered a potent pretreatment or adjuvant drug during the induction of anesthesia with its peripherally and centrally mediated analgesia. OBJECTIVE: The aim of this study was to compare the effects of pretreatment with hydromorphone in reducing rocuronium-induced withdrawal movements and hemodynamic changes during tracheal intubation with the effects of fentanyl and normal saline. METHODS: In this double-blind, randomized, controlled study, consecutive adult patients aged 20 to 70 years who were scheduled to undergo general anesthesia for elective gastric or colorectal surgery at the Samsung Seoul Hospital (Seoul, Republic of Korea) were randomly assigned to receive 5 mL hydromorphone 0.03 mg/kg or fentanyl 2 µg/kg or normal saline. Thirty seconds after administering the study drug, anesthesia was induced with 2.5% thiopental sodium 5 mg/kg. After loss of consciousness, rocuronium 0.6 mg/kg was injected and immediate withdrawal movements were recorded. Two minutes after rocuronium injection, tracheal intubation was performed and hemodynamic changes were observed. RESULTS: A total of 194 patients were enrolled, with 65 in the hydromorphone group, 67 in the fentanyl group, and 62 in the saline group. The overall incidence of withdrawal movements was significantly lower in the hydromorphone group (2 patients; 3.1%) and the fentanyl group (5 patients; 7.5%) (both, P < 0.001) than in the saline group (36 patients; 58.1%). The mean arterial pressure (MAP) and heart rate (HR) after intubation (median [interquartile range]) in the fentanyl group (101.5 [84-115] mm Hg; 93.5 [82-102] beats per minute [bpm]) and the hydromorphone group (93.0 [83-106] mm Hg; 90.0 [86.3-93.6] bpm) were significantly lower than these measures in the saline group (111.5 [105-123] mm Hg; 103.5 [96-113] bpm) (fentanyl group MAP and HR, P < 0.001; hydromorphone group MAP and HR, P < 0.001). CONCLUSIONS: Pretreatment with hydromorphone and fentanyl may have similar effectiveness in reducing withdrawal movements in response to rocuronium injection pain and inducing immediate general anesthesia.

Determination of adequate entry angle of lumbar sympathetic ganglion block in korean.

BACKGROUND: The target of lumbar sympathetic ganglion block is the anterolateral surface of the L2, 3 and 4 vertebral bodies, where the lumbar sympathetic ganglion usually lies. In most cases, a block-needle is inserted approximately 5-8 cm lateral to spinous process on the skin and directed to the anterolateral surface of vertebral body obliquely. The purpose of this study is to determine the safe entry angle and entry point in Korean by using the abdominal CT scan images. METHODS: The abdominal CT images of eighty five patients were recruited to this study. The minimal angle aimed at the lumbar sympathetic ganglion that can pass through the lateral aspect of body and maximal angle that avoids puncturing the kidney, ureter or retroperitoneal space were measured. The distance from midline to skin entry point was also measured. RESULTS: There was no significant difference in entry angle among L2, 3, and 4 level. The entry angle was similar in the right and left side, and in males and females. The entry angle of old age group was significantly smaller than that of young age group. The calculated safe entry angle was 30.5 +/- 0.4 degrees and entry point was 7.7 +/- 0.2 cm and 6.7 +/- 0.1 cm lateral from midline in males and females respectively. CONCLUSIONS: These measurements can be used as a reference for lumbar sympathetic ganglion block and radiofrequency lesioning. Prior to performing the lumbar sympathetic ganglion block for cancer patients, the abdominal CT scan should be reviewed to prevent complications.

Comparative analysis of the independent medical examination reports and legal decisions in pain medicine.

BACKGROUND: An independent medical examination (IME) is a critical process for awarding reparation for injury. However, conducting an IME in pain medicine is very difficult, not only because pain is a subjective symptom, but also because there are no proper objective methods to demonstrate it. This study was conducted to compare IME reports and the court decisions on the disability status of the patients. METHODS: We analyzed 79 IME reports and 25 corresponding court decisions on the disability status of patients. The diagnoses, causal relationships between the patients' status and the trauma, McBride's degree of disability, the American Medical Association's impairment ratings, the estimated annual cost for future treatment, and the necessity of care-giving were compared and analyzed. RESULTS: The diagnoses in the 79 cases were complex regional pain syndrome (CRPS) type I (58 cases), CRPS type II (7 cases), peripheral neuropathy (5 cases), myofascial pain syndrome (4 cases), herniated intervertebral disc (2 cases), and fibromyalgia (1 case). The types of accidents were road traffic accidents (50 cases), military injuries (14 cases), industrial accidents (11 cases), and others (4 cases). The IME reports and the court decisions stated considerably different McBride's degrees of disability (P = 0.014). However, there was no significant difference in the estimated cost for future treatment between the IME reports and the court decisions (P = 0.912). CONCLUSIONS: IME reports should be accurate, fair, and based on objective findings. Feedback on IMEs from the court decisions is helpful for reference use.