Discovery of BMS-986235/LAR-1219: A Potent Formyl Peptide Receptor 2 (FPR2) Selective Agonist for the Prevention of Heart Failure.

Formyl peptide receptor 2 (FPR2) agonists can stimulate resolution of inflammation and may have utility for treatment of diseases caused by chronic inflammation, including heart failure. We report the discovery of a potent and selective FPR2 agonist and its evaluation in a mouse heart failure model. A simple linear urea with moderate agonist activity served as the starting point for optimization. Introduction of a pyrrolidinone core accessed a rigid conformation that produced potent FPR2 and FPR1 agonists. Optimization of lactam substituents led to the discovery of the FPR2 selective agonist 13c, BMS-986235/LAR-1219. In cellular assays 13c inhibited neutrophil chemotaxis and stimulated macrophage phagocytosis, key end points to promote resolution of inflammation. Cardiac structure and functional improvements were observed in a mouse heart failure model following treatment with BMS-986235/LAR-1219.

[Tracheal Resection and Primary Anastomosis for Adenoid Cystic Carcinoma Using an Extracorporeal Membrane Oxygenation].

We report a case of tracheal resection and primary anastomosis for adenoid cystic carcinoma using an extracorporeal membrane oxygenation (ECMO). A 45-year-old female was referred to our hospital because of a tracheal tumor that occupied most of the tracheal lumen. In case of airway obstruction by the tracheal tumor during anesthesia and operation, we decided to use ECMO before induction of general anesthesia. Under secure respiratory control using ECMO, tracheal resection and primary anastomosis was performed. Since histopathological examination revealed microscopically positive results at the surgical margin, postoperative adjuvant radiation therapy( 60 Gy/30 Fr) was conducted. Although a tracheal tumor is a relatively rare neoplasm, careful planning and a treatment strategy are necessary with special emphasis on the location and size of tumor. In this case, ECMO made a substantial contribution to secure respiratory control during surgery.

Urinary retention occurring one week after spinal anesthesia: a case of Elsberg syndrome.

PURPOSE: We describe a case of urinary retention caused by viral sacral myeloradiculitis (Elsberg syndrome) that occurred one week after spinal anesthesia. The differential diagnosis of urinary retention after spinal anesthesia is discussed. CLINICAL FEATURES: A 76-yr-old male patient presented for operative removal of a right testicular hydrocele under spinal anesthesia. Anesthesia and surgery were uneventful, and he was discharged on the fifth postoperative day. Two days after discharge, he developed intermittent anal pain and voiding difficulty and was readmitted to hospital on the tenth postoperative day. He subsequently developed urinary retention, incontinence of feces, and difficulty in defecation. Magnetic resonance imaging showed no epidural hematoma, abscess, or other lesions in the spinal column, cauda equina, or spinal cord. Neurological examination showed dysesthesia in the perineal region and loss of the anal reflex and bulbocavernosus response, which indicated sacral (S4-5) radiculopathy or a lesion of the conus of the spinal cord. A cerebrospinal analysis showed slight elevation of protein without pleocytosis. After neurologic consultation, herpetic sacral myeloradiculitis was suspected and intravenous acyclovir was administered along with large doses of methylprednisolone and immunoglobulin. The symptoms gradually resolved, and the difficulty in voiding resolved 19 days after initiation of the treatment. The patient was discharged 23 days after the start of the treatment without any other complications. CONCLUSION: This case suggests that Elsberg syndrome is important in the differential diagnosis of urinary retention after spinal anesthesia and should be discriminated from other anesthesia-related complications.

[Study of nausea and vomiting accompanying intravenous patient-controlled analgesia with fentanyl after cervical spine surgery].

BACKGROUND: Serious side effects of postoperative analgesia with opioid drugs include nausea and vomiting. METHODS: We investigated the effects of various factors (patient background, anesthesia duration, and intraoperative drug use) on the frequency and degree of postoperative nausea and vomiting (PONV) during the first 24 hours of intravenous patient-controlled analgesia (PCA) with fentanyl. RESULTS: PONV occurred in 34% of the male patients and 68% of the female, and in 31% and 58% of smokers and non-smokers, respectively. CONCLUSIONS: Consideration should be given to gender and smoking status prior to starting preventive antiemetic therapy using PCA with fentanyl following cervical spine surgery.

[Postoperative continuous epidural analgesia with portable disposable infuser pump: review of 1500 cases].

BACKGROUND: We have been offering active postoperative analgesia service (PAS). In order to further enhance the quality of PAS, we reviewed 1500 cases of postoperative continuous epidural analgesia (PCEA). METHODS: Postoperative patients received epidural administration of a mixed analgesic solution employing bupivacaine, morphine, or fentanyl using a portable disposable infuser pump (PDIP) for at least 72 hours. Analgesic effects were assessed by using Prince Henry's scoring and the demand for additional analgesics. The frequency and causes of discontinued infusion were also evaluated. RESULTS: 83.9% of cases showed no complications. However, in 4.7% of cases infusion was discontinued because of side effects (nausea, vomiting, pruritus, lower limb motor block, and hypotension, etc.), in 4.1% because of dislodgment of the epidural catheter, in 3.4% because of disconnection, in 2.0% because the patient removing the catheter, and in 0.8% because of the condition of the catheter insertion site. CONCLUSION: These results indicate that to improve our method of PCEA with PDIP, we must re-assess our regimen used for continuous epidural infusion for postoperative pain relief, and develop measures to prevent side effects and complications.

[Assessment of preoperative anxiety in patients entering the operating room on foot using state-trait anxiety inventory].

The purpose of this prospective study was to assess the effect of walking into the operating room on preoperative anxiety level. Sixty non-premedicated patients scheduled for elective surgery were randomly divided into two groups based on how they were transported into the operating room. One group was carried on a stretcher (n = 30) and the other entered on foot under their own power (n = 30). A subjective assessment of anxiety was performed using a state-trait anxiety inventory (STAI) the day before surgery and on arrival at the operating room. STAI values were not increased in the operating room as compared to the day before surgery for either group and did not differ between groups, though they showed a high level of anxiety throughout the preoperative period. We conclude that walking into the operating room has no significant influence on preoperative anxiety level.