Induction of Cyclooxygenase-2 in Alveolar Macrophages after Acid Aspiration: Selective Cyclooxygenase-2 Blockade Reduces Interleukin-6 Production

Background: Gastric acid aspiration can result in acute lung injury. In this study, the authors determined whether alveolar macrophages express cyclooxygenase-2 as a source of inflammatory mediators after acid aspiration.

Methods: Seventy-five microliters of hydrochloric acid solution, pH 1.15, was instilled into one lung in mice. After exposure, alveolar macrophages were harvested, and competitive polymerase chain reaction and enzyme-linked immunosorbent assay were performed to measure expression of cyclooxygenase-1 and -2, interleukin-1beta and -6, tumor necrosis factor-alpha, and inducible nitric oxide synthase (iNOS). The authors used immunocytochemistry to demonstrate expression of cyclooxygenase-2 in alveolar macrophages. Selective cyclooxygenase-2 blockade using N-2(-cyclohexyloxy-4-nitrophenyl) methane-sulphonamide was done to characterize prostaglandin-cytokine interaction.

Results: Acid aspiration induced upregulation of cyclooxygenase-2 and interleukin-6. Tumor necrosis factor-alpha and iNOS were not upregulated. Interleukin-1beta was upregulated even with saline instillation but could not be detected in the supernatant of the cell culture. Alveolar macrophages harvested from mice instilled with acid showed a trend toward more production of prostaglandin E2 and produced higher concentrations of interleukin-6 compared with alveolar macrophages from mice instilled with saline. Selective cyclooxygenase-2 blockade significantly decreased release of interleukin-6 from alveolar macrophages harvested from mice instilled with acid.     

A Single Preoperative Oral Dose of Valdecoxib, a New Cyclooxygenase-2 Specific Inhibitor, Relieves Post-Oral Surgery or Bunionectomy Pain

Background: The trend toward day-case surgery, with discharge on oral medication, has highlighted the need for effective and safe analgesics that facilitate a rapid recovery and discharge time. This study evaluated the analgesic efficacy, dose dependency, duration of action, and safety of the cyclooxygenase-2 specific inhibitor, valdecoxib, administered before oral or orthopedic surgery.

Methods: Eligible healthy adult patients were scheduled to undergo either extraction of two impacted third molar teeth (n = 284) or bunionectomy surgery (n = 223) with local anesthesia in two randomized, double-blind, placebo-controlled studies conducted at three centers in the United States. Patients received a single, preoperatively administered oral dose of placebo or 10 (oral surgery only), 20, 40, or 80 mg valdecoxib. Analgesic efficacy was assessed postoperatively, over a 24-h treatment period, or until the patient required rescue medication. Efficacy measures included time to rescue medication, proportion of patients requiring such rescue, pain intensity, and the Patient's Global Evaluation of Study Medication.

Results: In both studies, all doses of valdecoxib produced analgesia with a duration (time to rescue analgesia) and magnitude (Pain Intensity, Patient's Global Evaluation) significantly greater than placebo. A dose-dependent effect was observed up to 40 mg valdecoxib, with an 80-mg dose providing no additional analgesic benefit. In both models, all doses of valdecoxib were well tolerated, with no clinically significant treatment-related gastrointestinal, renal, or platelet-derived adverse events, and no evidence of a dose-related increase in adverse events.     

Safety and Efficacy of the Cyclooxygenase-2 Inhibitors Parecoxib and Valdecoxib after Noncardiac Surgery

Background: Valdecoxib and its intravenous prodrug parecoxib are reported to increase thromboembolic risk after coronary artery bypass grafting. The authors conducted a randomized trial to examine their safety and analgesic efficacy in patients recovering from major noncardiac surgical procedures.

Methods: The trial was randomized and double-blind, with 10 days of treatment and 30 days of follow-up. Patients (n = 1,062) received either parenteral parecoxib for 3 days and oral valdecoxib for the rest of the treatment period or placebo medications throughout. The frequency of predefined adjudicated postrandomization adverse events, including cardiovascular thromboembolism, renal dysfunction, gastroduodenal ulceration, and wound-healing complications, was assessed in each group. Secondary efficacy endpoints included patients' pain ratings, opioid analgesic consumption (recorded as morphine equivalents), and reports of opioid-related adverse effects.

Results: Predefined adjudicated adverse events had similar frequencies among patients who received parecoxib and valdecoxib (2.7%) and placebo patients (3.2%) (P = 0.58), including cardiovascular thromboembolic events (1.0% in each group; P = 1.0). Placebo patients consumed more morphine equivalents (66.2 +/- 92.4 mg) than did patients receiving parecoxib and valdecoxib (43.2 +/- 65.7 mg) (P < 0.001). Placebo patients had higher mean pain ratings on each of study days 2-10 (P < 0.01) and reported more opioid-related symptom distress on days 2-6 (P < 0.01).     

Selective Targeting of High‐Affinity LFA‐1 Does Not Augment Costimulation Blockade in a Nonhuman Primate Renal Transplantation Model

Costimulation blockade (CoB) via belatacept is a lower‐morbidity alternative to calcineurin inhibitor (CNI)‐based immunosuppression. However, it has higher rates of early acute rejection. These early rejections are mediated in part by memory T cells, which have reduced dependence on the pathway targeted by belatacept and increased adhesion molecule expression. One such molecule is leukocyte function antigen (LFA)‐1. LFA‐1 exists in two forms: a commonly expressed, low‐affinity form and a transient, high‐affinity form, expressed only during activation. We have shown that antibodies reactive with LFA‐1 regardless of its configuration are effective in eliminating memory T cells but at the cost of impaired protective immunity. Here we test two novel agents, leukotoxin A and AL‐579, each of which targets the high‐affinity form of LFA‐1, to determine whether this more precise targeting prevents belatacept‐resistant rejection. Despite evidence of ex vivo and in vivo ligand‐specific activity, neither agent when combined with belatacept proved superior to belatacept monotherapy. Leukotoxin A approached a ceiling of toxicity before efficacy, while AL‐579 failed to significantly alter the peripheral immune response. These data, and prior studies, suggest that LFA‐1 blockade may not be a suitable adjuvant agent for CoB‐resistant rejection.     

Intraoperative Ketorolac Use Does Not Increase the Risk of Bleeding in Breast Surgery

Annals of Surgical Oncology - The use of nonsteroidal anti-inflammatory drugs is an effective adjunct in managing perioperative pain. We sought to determine if the use of intraoperative ketorolac...     

Postoperative Morphine Use and Hyperalgesia Are Reduced by Preoperative but Not Intraoperative Epidural Analgesia: Implications for Preemptive Analgesia and the Prevention of Central Sensitization

Background: The aim of this study was to evaluate the postoperative morphine-sparing effects and reduction in pain and secondary mechanical hyperalgesia after preincisional or postincisional epidural administration of a local anesthetic and an opioid compared with a sham epidural control.

Methods: Patients undergoing major gynecologic surgery by laparotomy were randomly assigned to three groups and studied in a double-blinded manner. Group 1 received epidural lidocaine and fentanyl before incision and epidural saline 40 min after incision. Group 2 received epidural saline before incision and epidural lidocaine and fentanyl 40 min after incision. Group 3 received a sham epidural control (with saline injected into a catheter taped to the back) before and 40 min after incision. All patients underwent surgery with general anesthesia.

Results: One hundred forty-one patients completed the study (group 1, n = 45; group 2, n = 49; group 3, n = 47). Cumulative patient-controlled analgesia morphine consumption at 48 h was significantly lower (P = 0.04) in group 1 (89.8 +/- 43.3 mg) than group 3 (112.5 +/- 71.5 mg) but not group 2 (95.4 +/- 60.2 mg), although the hourly rate of morphine consumption between 24 and 48 h after surgery was significantly lower (P < 0.0009) in group 1 (1.25 +/- 0.02 mg/h) than group 2 (1.41 +/- 0.02 mg/h). Twenty-four hours after surgery, the visual analog scale pain score on movement was significantly less intense (P = 0.005) in group 1 (4.9 +/- 2.2 cm) than group 3 (6.0 +/- 2.6 cm) but not group 2 (5.3 +/- 2.5 cm), and the von Frey pain threshold near the wound was significantly higher (P = 0.03) in group 1 (6.4 +/- 0.6 log mg) than in group 3 (6.1 +/- 0.8 log mg) but not group 2 (6.2 +/- 0.7 log mg).     

Preoperative Interventions and Charges in the 2-Year Period Before Unicompartmental Knee Arthroplasty: What Happens Before Surgery

Background

This study investigated preoperative interventions and their costs in the 2-year period before a patient undergoing a unicompartmental knee arthroplasty (UKA).

Remission of Type 2 Diabetes Mellitus Should Not Be the Foremost Goal after Bariatric Surgery

Background

Remission of type 2 diabetes (T2D) is a desired outcome after bariatric surgery (BS). Even if this goal is not achieved, individuals who do not strictly fulfill remission criteria experience an overall improvement. The aim of this study was to evaluate the metabolic control status in patients considered as diabetes “non-remitters.”

Methods

A retrospective study of 125 patients (59.2 % women) with preoperative diagnosis of T2D who underwent BS in a single center (2006–2011) was conducted. We collected anthropometric and metabolic parameters before surgery and at 1-year follow-up. T2D remission was defined according to the 2009 consensus statement: glycosylated hemoglobin (HbA1c) <6 %, fasting glucose (FG) <100 mg/dLs, and absence of pharmacologic treatment. We evaluated metabolic status of non-remitters, according to the American Diabetes Association's (ADA) target recommendations: HbA1c <7 %, LDL-c <100 mg/dL, triglycerides <150 mg/dL, and HDL-c >40 (male) or >50 mg/dL (female). Statistics: analysis of variance.

Results

Baseline characteristics (mean ± SD): age 53.5?±?9.7 years, BMI 43.5?±?5.6 kg/m², time since diagnosis of T2D 7.7?±?7.9 years, FG 162.0?±?56.3 mg/dL, HbA1c 7.7?±?1.6 %. ADA's target recommendations were present in 12 patients (9.6 %) preoperatively, and in 45 (36.0 %) at 1-year follow-up (p <0.001). Sixty-two (49.6 %) patients did not achieve diabetes remission; 26 (41.9 %) had now diet treatment, 30 (48.4 %) oral medications, and 6 (9.7 %) required insulin. Of the non-remitters, 57 (91.9 %) had HbA1c <7 % and 18 (40.0 %) achieved ADA's target recommendations. There were no differences between remitters and non-remitters in the number of individuals reaching ADA's combined metabolic control.

Conclusions

Although almost 50 % of the patients may not be classified as diabetes remitters, their significant improvement in metabolic control should be regarded as a success, according to most scientific societies' target recommendations.     

Comparison of Intravenous or Epidural Patient-controlled Analgesia in the Elderly after Major Abdominal Surgery

Background: Patient-controlled analgesia (PCA) with intravenous morphine and patient-controlled epidural analgesia (PCEA), using an opioid either alone or in combination with a local anesthetic, are two major advances in the management of pain after major surgery. However, these techniques have been evaluated poorly in elderly people. This prospective, randomized study compared the effectiveness on postoperative pain and safety of PCEA and PCA after major abdominal surgery in the elderly patient.

Methods: Seventy patients older than 70 yr of age and undergoing major abdominal surgery were assigned randomly to receive either combined epidural analgesia and general anesthesia followed by postoperative PCEA, using a mixture of 0.125% bupivacaine and sufentanil (PCEA group), or general anesthesia followed by PCA with intravenous morphine (PCA group). Pain intensity was tested three times daily using a visual analog scale. Postoperative evaluation included mental status, cardiorespiratory and gastrointestinal functions, and patient satisfaction scores.

Results: Pain relief was better at rest (P = 0.001) and after coughing (P = 0.002) in the PCEA group during the 5 postoperative days. Satisfaction scores were better in the PCEA group. Although incidence of delirium was comparable in the PCA and PCEA groups (24%vs. 26%, respectively), mental status was improved on the fourth and fifth postoperative days in the PCEA group. The PCEA group recovered bowel function more quickly than did the PCA group. Cardiopulmonary complications were similar in the two groups.     

围生期新生儿行艾滋病病毒阻断治疗的护理

对11例艾滋病病毒感染孕妇分娩的新生几采取药物阻断治疗、人工喂养、新生儿健康指导及血清HIV检测的意义指导等护理措施。结果新生几住院期间无并发症及死亡病例，1例2岁死亡，4例仍在随访中．6例失访。     

围生期新生儿行艾滋病病毒阻断治疗的护理

对11例艾滋病病毒感染孕妇分娩的新生儿采取药物阻断治疗、人工喂养、新生儿健康指导及血清HIV检测的意义指导等护理措施。结果新生儿住院期间无并发症及死亡病例。1例2岁死亡,4例仍在随访中,6例失访。     

Perioperative Administration of Selective Cyclooxygenase-2 Inhibitors for Postoperative Pain Management in Patients After Total Knee Arthroplasty

Total knee arthroplasty (TKA) is associated with considerable postoperative pain. The relative analgesic efficacy and adverse effect profile of perioperative use of selective cyclooxygenase-2 (COX-2) inhibitors for patients undergoing TKA are unclear. This is a systematic review and meta-analysis of all randomized controlled trials evaluating perioperative administration of COX-2 inhibitors for TKA. Eight studies that had enrolled a total of 571 patients were identified. There was a statistical significance in postoperative pain scores (0-24 hours: P = .0007, 24-48 hours: P = .01, 48-72 hours: P < .0001), opioid consumption (P = .006), active range of motion (P = .002), itching (P = .005), and postoperative nausea/vomiting (P = .003) between groups. There was no difference in blood loss during the first 24 hours after operation between groups. The efficacy of perioperative administration of selective COX-2 inhibitors to reduce postoperative pain and opioid consumption after TKA is validated. Furthermore, it has important outcome benefits after TKA.