Reasons for discontinuation of acute postoperative pain ketamine infusions: A retrospective case-control study.

PURPOSE: The purpose of the study was to investigate factors associated with early discontinuation of low-dose ketamine infusions due to adverse drug events (ADEs). METHODS: A retrospective, matched case-control study of surgical patients who received low-dose ketamine infusions for postoperative pain over 6 years was conducted. Forty-seven study patients, who required early discontinuation of their infusion due to ADEs, were included and matched 1:1 with 47 controls, who did not experience ADEs, for a total of 94 patients. The two groups were compared based on surgery type, American Society of Anesthesiologists (ASA) classification, administration of specific perioperative anxiolytic, anesthetic, and analgesic medications, and use of regional anesthesia. RESULTS: Of the study patients, 44.7% underwent spine procedures (vs. 34% of controls), 27.6% underwent abdominal procedures (vs. 8.5% of controls), 19.2% underwent orthopedic procedures (vs. 46.8% of controls), and 8.5% underwent thoracic procedures (vs. 6.4% of controls). There were no statistically significant differences in ASA classification, pre-operative gabapentinoid and antidepressant use, average ketamine infusion dose, or postoperative use of peripheral nerve catheters, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, muscle relaxants, and nonbenzodiazepine sleep aides. Study patients had higher rates of intra-operative volatile anesthetic use (78.7% vs. 57.7%, p = 0.03) and more postoperative opioid patient-controlled analgesia (PCA) use (53.2% vs. 29.8%, p = 0.02) than controls. Control patients had higher rates of preoperative opioid use (76.7% vs. 53.2%, p = 0.02) and premedication with midazolam (89.4% vs. 70.2%, p = 0.02) than study patients. CONCLUSION: Patients who required discontinuation of their low-dose ketamine infusion due to ADEs were more likely to be opioid naïve, received less pre-operative benzodiazepines, and had greater postoperative opioid PCA requirements. Control patients, on the other hand, had higher rates of pre-operative opioid use and experienced fewer ADEs despite greater total ketamine doses.

Nonterpenoid C15 acetogenins from Laurencia marilzae.

Eight new halogenated C(15) acetogenins, 1-8, were isolated from the organic extract of the red alga Laurencia marilzae. The structure elucidation and the assignments of the relative configurations were established by extensive use of spectroscopic studies, particularly 1D and 2D NMR data, while the absolute configurations of compounds 1 and 5 were determined by single-crystal X-ray diffraction analysis. Compounds 1, 2, 4, 5, and 7, along with the previously reported related cyclic ether obtusallene IV (9), were evaluated against six human solid tumor cell lines. All compounds were found to be essentially inactive (GI(50) > 10 µg/mL).

Counting ribs and thoracic levels under ultrasound: a systematized technical protocol for both posterior and anterior approaches.

Over the last two decades, the clinical applications of diagnostic and interventional ultrasound have expanded rapidly. When analyzing the chest wall and thoracic region, ultrasound has previously been shown to reliably identify chest wall pathologies like rib fracture and slipping rib syndrome, as well as having fundamentally changed perioperative management and patient outcomes after the emergence of point-of-care ultrasound. In addition, ultrasound guidance has recently become more popular for multiple blocks in the field of regional anesthesia and pain medicine. In this technical report, we systematize an ultrasound-guided protocol for counting ribs and thoracic levels for both posterior and anterior approaches, which does not require level confirmation by fluoroscopy. With this protocol, we hope to create an effective educational resource to support physicians from any specialty background as they engage in point-of-care ultrasound applications in the thoracic region.

Detection and identification of glycoyessotoxin A in a culture of the dinoflagellate Protoceratium reticulatum.

The toxin composition of a culture of the dinoflagellate Protoceratium reticulatum was investigated using LC-FLD, after derivatization with DMEQ-TAD (4-(2-(6,7-dimethoxy-4-methyl-3-oxo-3,4-dihydroquinoxalimylethyl)-1,2,4-triazoline-3,5-dione)). Besides yessotoxin (YTX), the new YTX analogue, glycoyessotoxin A (G-YTXA) was detected in culture medium as well as in cells. The conditions for extraction were optimized and the production profile established. Retention time of the resulting fluorescent G-YTXA adduct was identified by comparison of the appropriate standard. Additionally, both G-YTXA and the DMEQ-TAD-G-YTXA adduct were confirmed by LC-MS showing ion peaks at m/z 1273 [M-2Na+H](-) and m/z 1618 [M-2Na+H](-), respectively. The LC-MS(n) displayed a fragmentation pattern similar to that of the YTX series.

Identification of conserved and HLA promiscuous DENV3 T-cell epitopes.

Anti-dengue T-cell responses have been implicated in both protection and immunopathology. However, most of the T-cell studies for dengue include few epitopes, with limited knowledge of their inter-serotype variation and the breadth of their human leukocyte antigen (HLA) affinity. In order to expand our knowledge of HLA-restricted dengue epitopes, we screened T-cell responses against 477 overlapping peptides derived from structural and non-structural proteins of the dengue virus serotype 3 (DENV3) by use of HLA class I and II transgenic mice (TgM): A2, A24, B7, DR2, DR3 and DR4. TgM were inoculated with peptides pools and the T-cell immunogenic peptides were identified by ELISPOT. Nine HLA class I and 97 HLA class II novel DENV3 epitopes were identified based on immunogenicity in TgM and their HLA affinity was further confirmed by binding assays analysis. A subset of these epitopes activated memory T-cells from DENV3 immune volunteers and was also capable of priming naïve T-cells, ex vivo, from dengue IgG negative individuals. Analysis of inter- and intra-serotype variation of such an epitope (A02-restricted) allowed us to identify altered peptide ligands not only in DENV3 but also in other DENV serotypes. These studies also characterized the HLA promiscuity of 23 HLA class II epitopes bearing highly conserved sequences, six of which could bind to more than 10 different HLA molecules representing a large percentage of the global population. These epitope data are invaluable to investigate the role of T-cells in dengue immunity/pathogenesis and vaccine design.

Glycoyessotoxin a, a new yessotoxin derivative from cultures of Protoceratium reticulatum.

The dinoflagellate Protoceratium reticulatum produces toxins of the yessotoxin group currently included in the diarrhetic shellfish poisoning class. In this paper we report on the isolation and structural elucidation of a 32-arabinoside of yessotoxin, G-YTXA (2), obtained from laboratory cultures of P. reticulatum (strain GG1AM) that possesses a pentose unit, beta-arabinofuranose, as a side chain.