Improvement in postoperative pain control by combined use of intravenous dexamethasone with intravenous dexmedetomidine after interscalene brachial plexus block for arthroscopic shoulder surgery: A randomised controlled trial.

BACKGROUND: Intravenous dexamethasone or dexmedetomidine is reported to prolong the duration of analgesia after single-shot interscalene brachial plexus block (ISBPB). However, the effect of co-administration of these agents on the duration of analgesia has not been evaluated. OBJECTIVES: We evaluated the difference in time to first rescue analgesic request between patients receiving co-administered intravenous dexamethasone and dexmedetomidine and patients receiving intravenous dexamethasone alone after single-shot ISBPB for arthroscopic shoulder surgery. DESIGN: A randomised controlled study. SETTING: A single tertiary care centre, study period from August 2017 to January 2018. PATIENTS: Sixty-six patients undergoing arthroscopic shoulder surgery with ISBPB with 15 ml of 0.5% ropivacaine with 1 : 200 000 epinephrine. INTERVENTIONS: We randomly assigned the patients to one of three groups: intravenous 0.9% saline (control), intravenous dexamethasone 0.11 mg kg (D1 group), or co-administered intravenous dexamethasone 0.11 mg kg and intravenous dexmedetomidine 1.0 µg kg (D2 group). MAIN OUTCOME MEASURES: The primary outcome was the time to first rescue analgesic request. RESULTS: The median [interquartile range] time to first rescue analgesic request was significantly longer for the D2 group (66.3 h [23.3 to 72]) than the D1 (17.4 h [14.9 to 36], P = 0.002) and control (10.9 h [10.1 to 12.2], P < 0.001) groups. The D1 and D2 groups both had reduced pain scores, reduced postoperative opioid consumption, less sleep disruption and improved patient satisfaction compared with the control group. There were no significant elevations in blood glucose concentrations in patients receiving dexamethasone (D1 and D2 groups) compared with the control group at postoperative day 1. CONCLUSION: Co-administration of intravenous dexamethasone (0.11 mg kg) with dexmedetomidine (1.0 µg kg) significantly prolonged the time to first rescue analgesic request after single-shot ISBPB in patients undergoing arthroscopic shoulder surgery. TRIAL REGISTRATION: Clinical Trial Registry of Korea; https://cris.nih.go.kr/cris/index.jsp and identifier: KCT0002569.

AKT Inhibition Promotes Nonautonomous Cancer Cell Survival.

Small molecule inhibitors of AKT (v-akt murine thymoma viral oncogene homolog) signaling are being evaluated in patients with various cancer types, but have so far proven therapeutically disappointing for reasons that remain unclear. Here, we treat cancer cells with subtherapeutic doses of Akti-1/2, an allosteric small molecule AKT inhibitor, in order to experimentally model pharmacologic inhibition of AKT signaling in vitro. We then apply a combined RNA, protein, and metabolite profiling approach to develop an integrated, multiscale, molecular snapshot of this "AKT(low)" cancer cell state. We find that AKT-inhibited cancer cells suppress thousands of mRNA transcripts, and proteins related to the cell cycle, ribosome, and protein translation. Surprisingly, however, these AKT-inhibited cells simultaneously upregulate a host of other proteins and metabolites posttranscriptionally, reflecting activation of their endo-vesiculo-membrane system, secretion of inflammatory proteins, and elaboration of extracellular microvesicles. Importantly, these microvesicles enable rapidly proliferating cancer cells of various types to better withstand different stress conditions, including serum deprivation, hypoxia, or cytotoxic chemotherapy in vitro and xenografting in vivo. These findings suggest a model whereby cancer cells experiencing a partial inhibition of AKT signaling may actually promote the survival of neighbors through non-cell autonomous communication.

Efficacy and safety of a novel botulinum toxin type A product for the treatment of moderate to severe glabellar lines: a randomized, double-blind, active-controlled multicenter study.

BACKGROUND: A new botulinum toxin type A (NBoNT) produced from the same strain of Clostridium botulinum as onabotulinumtoxinA (OBoNT) is widely used in Asia. OBJECTIVES: To compare the efficacy and safety of NBoNT and OBoNT for moderate to severe glabellar wrinkles. METHODS: A double-blind, randomized, active-controlled, phase III study was performed. Three hundred fourteen patients were randomized at a 1:1 ratio to receive 20 U of toxin. The primary end point was the responder rate according to investigator live assessment at maximum frown at week 4. Secondary end points were responder rates according to investigator live assessment with frowning and at rest at weeks 8, 12, and 16, with additional photographic assessment by a panel of blinded raters 4 weeks after injection. Subjective satisfaction scores were also evaluated. RESULTS: Four weeks after treatment, responder rates for maximum frown were 93.7% (133/142) in the NBoNT group and 94.5% (138/146) in the OBoNT group. For secondary end points, there was no significant difference between the two groups for any variable at any time point. Noninferiority of NBoNT was confirmed. There were no serious adverse effects with either toxin. CONCLUSION: NBoNT is equally as effective as OBoNT for the treatment of glabellar frown lines. Both toxins were well tolerated.

Peripheral administration of NR2 antagonists attenuates orofacial formalin-induced nociceptive behavior in rats.

The present study investigated the role of the peripheral NR2 subunits of N-methyl-d-aspartatic acid (NMDA) receptors in inflammatory orofacial pain. Experiments were carried out using adult male Sprague-Dawley rats weighing 220 to 280 g. Formalin (5%, 50 µl) was applied subcutaneously to the vibrissa pad. For each animal, the number of noxious behavioral responses, including rubbing or scratching of the facial region proximal to the injection site, was recorded for 9 sequential 5 min intervals. NR2 subunit antagonists were injected subcutaneously at 20 min prior to formalin injection. The subcutaneous injection of 100 or 200 µg of memantine significantly suppressed the number of scratches in the second phase of the behavioral responses to formalin. The subcutaneous injection of 0.25, 2.5, or 25 µg of 5,7-dichlorokynurenic acid also produced significant antinociceptive effects in the second phase. The subcutaneous injection of AP-5 at high dose produced significant antinociceptive effects in the second phase. The subcutaneous injection of PPPA and Ro 25-6981 both significantly suppressed the number of scratches in the second phase. The antinociceptive doses of memantine (200 µg), 5,7-dichlorokynurenic acid (25 µg), AP-5 (20 µg), PPPA (2.5 µg), or Ro 25-6981 (50 µg) injected into the contralateral hind paw did not affect the number of scratches in both the first and second phases. Moreover, the peripheral administration of NR2 subunit antagonists, including other NMDA receptor blockers, did not produce any motor dysfunction. These results indicate that a targeted blockade of peripheral NR2 receptors is a potentially important new method of treating inflammatory pain in the orofacial area.

Generation of donor natural killer cells from CD34(+) progenitor cells and subsequent infusion after HLA-mismatched allogeneic hematopoietic cell transplantation: a feasibility study.

Post transplant infusion of donor-type natural killer (NK) cells has been shown to have an anti-leukemia-enhancing effect without evoking GVHD in murine hematopoietic cell transplantation (HCT) models. Here, we tested 14 patients (age, 23-65 years), 12 with acute leukemia and 2 with myelodysplastic syndrome, who underwent HLA-mismatched HCT and subsequently received donor NK cell infusions. Cell donors (age, 16-51 years), comprising seven siblings, five offspring, and two mothers of the patients, underwent growth factor-mobilized leukapheresis for 3-5 days. Cells collected on the first 2-4 days were used for HCT, whereas those collected on the last day were CD34 selected by magnetic-activated cell sorting (median, 2.22 x 10(6) cells/kg; range, 0.29-5.66). Donor NK cells were generated from the CD34(+) cells by ex vivo cell culture over a 6-week period (median, 9.28 x 10(6) cells/kg; range, 0.33-24.50; CD122/CD56(+) 64%; CD3(+) 1.0%; and viability 88%). There were no signs of acute toxicity in patients infused with these cells 6-7 weeks post transplant. Overall, one and five patients developed acute and chronic GVHD during post transplant period, respectively. These results showed that clinical-grade donor NK cell production from CD34(+) cells is feasible.

Adjacent crosstalk suppression in a colorless WDM passive optical network.

We propose and experimentally demonstrate a novel wavelength-division- multiplexed passive optical network (WDM-PON) scheme for the suppression of adjacent crosstalk arising from the wavelength misalignment in arrayed waveguide gratings (AWGs) between a central office (CO) and a remote node (RN). The adjacent crosstalk suppression is achieved by allocating two different bands to adjacent channels of the AWGs by utilizing interleavers and WDM filters. The transmission performance of the proposed scheme was measured at a 155 Mb/s data stream, and error free transmission with a power penalty less than 0.7 dB was successfully achieved in case of AWG misalignment of 0.3 nm.

Factors affecting the angiographic recanalization and early clinical improvement in middle cerebral artery territory infarction after thrombolysis.

BACKGROUND: Factors affecting the angiographic recanalization (AR) and clinical improvement (CI) still remain unclear in patients receiving thrombolytic therapy. OBJECTIVES: To elucidate factors related to AR and early CI in patients with middle cerebral artery (MCA) or internal carotid artery (ICA) occlusion. DESIGNS: Retrospective study. SETTING: Department of Neurology, Asan Medical Center, Seoul, South Korea. PATIENTS: We studied 42 patients who (1) underwent diffusion-weighted magnetic resonance (MR) imaging and MR angiography within 6 hours after onset, (2) had MCA territory infarction, (3) had nonvisualization of the MCA or the ICA on initial MR angiography, (4) were treated with thrombolytics, and (5) underwent follow-up MR imaging and MR angiography at day 2 or 3. RESULTS: Successful AR and CI were achieved in 31 and 16 patients, respectively. Angiographic recanalization was related to CI (P<.01), lower follow-up National Institutes of Health Stroke Scale scores (P<.05), the absence of a dominant ipsilateral posterior cerebral artery (P<.01) on initial MR angiography, and the sparing of the internal capsule on both initial (P<.05) and follow-up (P<.01) MR imaging. Clinical improvement was associated with the absence of ICA (vs MCA) flow signals (P<.05), the sparing of the internal capsule (P<.01), and marginally, with the infarct volume change (P = .06). CONCLUSIONS: In patients with MCA or ICA occlusion, CI after thrombolysis is related to the AR and the sparing of the critical motor pathway. The presence of a dominant ipsilateral posterior cerebral artery may predict poor AR after thrombolysis.

Percutaneous transluminal angioplasty for symptomatic middle cerebral artery stenosis: long-term follow-up.

BACKGROUND AND OBJECTIVE: Although percutaneous transluminal angioplasty (PTA) is an effective treatment modality in the coronary and peripheral arterial diseases, its efficacy for intracranial atherosclerotic stenosis has not been verified. We assessed the long-term outcome of PTA for symptomatic middle cerebral artery (MCA) stenosis. METHODS: We performed PTA in 10 patients with symptomatic high-grade stenosis (>70%) on M1 segment of MCA, who had either recurrent transient ischemic attacks (TIAs) resistant to medical therapy or perfusion problems. PTA was performed with a microballoon (2-2.5 mm diameter and 10-13 mm length) without insertion of a stent. After PTA, we evaluated the possible occurrence of restenosis, which was defined as >50% stenosis on follow-up conventional angiogram or increased M1 flow velocity on follow-up transcranial doppler up to the baseline value. RESULTS: PTA was successfully performed in 9 patients without any serious complications. One patient had asymptomatic dissection. Residual stenosis was less than 50% in diameter in all the patients. During follow-up period (mean 34.5 months), TIAs did not recur in 6 of 7 patients who had had intractable TIAs. Two patients developed strokes, which were not referable to the index MCA lesions. Among the 6 patients who underwent follow-up conventional angiography or serial TCD, restenosis was noticed in 3 patients (50%). CONCLUSION: Although restenosis is not uncommon, PTA for symptomatic MCA stenosis is a relatively safe procedure, and can be used to prevent recurrent TIAs or strokes in selected patients.