The most feared drug-induced complication is fatal cardiac arrest. Torsades de pointes (TdP) is a polymorphic ventricular tachycardia occurring in the setting of a QT interval prolongation and is the most frequent type of drug-induced pro-arrhythmia. The most common mechanism of QT prolongation and TdP is blockade of the rapid component of the delayed rectifier repolarizing potassium conductance IKr. Anesthesiologists have extensive experience with QT prolonging drugs, but there are relatively few reports of TdP occurring in the perioperative setting. Nevertheless, regulatory concern regarding the drug droperidol resulted in a significant reduction in its use. Concern regarding two other agents that potently block IKr, i.e., sevoflurane and methadone, has grown, and practitioners are worried that these valuable agents may meet the same fate. In this review, the data regarding the TdP risk of droperidol, sevoflurane, and methadone are compared with particular emphasis on the different settings in which they are employed. While the three drugs are potent IKr inhibitors, little evidence exists to suggest that droperidol or sevoflurane are associated with significant proarrhythmia in the perioperative setting. Due to factors such as inhibition of the parasympathetic nervous system, prevention of hypoxia and hypercarbia, and attention to serum electrolytes, TdP is a very rare occurrence in the perioperative environment. Methadone, however, is typically given to outpatients, over long periods, and in combination with agents that inhibit its metabolism or are QT prolonging in their own right. Thus, pre- and post-drug electrocardiograms may be appropriate when prescribing methadone for outpatients, while the much lower risk for TdP (and the difficulties inherent in QT measurement in the perioperative period) render this approach unfruitful and worthy of reevaluation.

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Humoral tumor-specific immunity has been investigated as a potential tool to identify tumor-associated antigens and evaluate cancer diagnosis and prognosis. Using SDS-PAGE and western blotting techniques we investigated the humoral immune response against tumor cell antigens in 36 breast cancer patients, 17 node-positive (NP) and 19 node-negative (NN). As a source of antigens, we prepared protein lysates from four breast cancer cell lines (AU565, BT474, MCF-7 and MDA-MB-231) which in vitro exhibit different features of invasion, estrogen receptor/progesterone receptor status and HER2/neu expression thereby potentially representing mild to aggressive forms of clinical disease. A higher number of immunocomplexes Ag-Ab were formed when serum from NN patients was immunoreacted against lysates from AU565 and MCF-7 in comparison to serum from NP patients (P < 0.01). BT474 cells were not a good antigenic source. MDA-MB-231 cells could not significantly discriminate between NN and NP patients since both groups showed higher amounts of reactivity against the lysate. However, comparative analysis of protein preparations purified from MCF-7 and MDA-MB-231 cells and immunodetected concomitantly with the same serum samples showed that serum from patients with cancers with worse prognosis (stage, nodality, HER2/neu and hormonal status) reacted more intensely to proteins purified from the relatively more invasive cell line MDA-MB-231 compared to MCF-7. These findings suggest that the study of serum antibody reactivity to antigens purified from breast cancer cell lines with different invasive properties should be further investigated for its potential in providing beneficial prognostic information in breast cancer.

IntroductionIn spite of advances in understanding and technology, postoperative pain remains poorly treated for a significant number of patients. In colorectal surgery, the need for developing novel analgesics is especially important. Patients after bowel surgery are assessed for rapid return of bowel function and opioids worsen ileus, nausea and constipation. We describe a prospective, double-blind, parallel group, placebo-controlled randomised controlled trial testing the hypothesis that a novel analgesic drug, VVZ -149, is safe and effective in improving pain compared with providing opioid analgesia alone among adults undergoing laparoscopic colorectal surgery.Methods and analysisBased on sample size calculations for primary outcome, we plan to enrol 120 participants. Adult patients without significant medical comorbidities or ongoing opioid use and who are undergoing laparoscopic colorectal surgery will be enrolled. Participants are randomly assigned to receive either VVZ-149 with intravenous (IV) hydromorphone patient-controlled analgesia (PCA) or the control intervention (IV PCA alone) in the postoperative period. The primary outcome is the Sum of Pain Intensity Difference over 8 hours (SPID-8 postdose). Participants receive VVZ-149 for 8 hours postoperatively to the primary study end point, after which they continue to be assessed for up to 24 hours. We measure opioid consumption, record pain intensity and pain relief, and evaluate the number of rescue doses and requests for opioid. To assess safety, we record sedation, nausea and vomiting, respiratory depression, laboratory tests and ECG readings after study drug administration. We evaluate for possible confounders of analgesic response, such as anxiety, depression and catastrophising behaviours. The study will also collect blood sample data and evaluate for pharmacokinetic and pharmacodynamic relationships.Ethics and disseminationEthical approval of the study protocol has been obtained from Institutional Review Boards at the participating institutions. Trial results will be disseminated through scientific conference presentations and by publication in scientific journals.Trial registration numberNCT02489526; pre-results.

Phantom limb pain is a common consequence of limb amputation and is prevalent among the service members sustaining traumatic battlefield limb injuries during the conflicts in Iraq and Afghanistan. Current treatment to relieve phantom limb pain consists of physical, behavioral, and medical modalities including opioids and adjunct medications. Treatment failure resulting in persistent pain and disability may result. This case series describes four previously healthy service members who developed phantom limb pain following traumatic amputation successfully treated with buprenorphine/naloxone after failing traditional treatment. This is the first reported case series of patients expressing improved pain control with decreased frequency of phantom limb pain with the use of buprenorphine/naloxone instead of traditional opioid agonists.