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Abstract: Depth of anaesthesia is difficult to measure accurately, but attempts have been made to measure it and to reduce the incidence of all causes of awareness. The incidence of awareness in non-cardiac and non-obstetric surgery is 0.07–0.2% but in emergency caesarean sections under general anaesthesia incidence increases to 0.4% and for cardiac surgery incidence is 1.1–1.5%. However, awareness is rare and studies advocating the merits of the various techniques generally aim at primary end points other than awareness. Common methods for monitoring depth of anaesthesia are clinical assessment. Historically this was measured using pulse, blood pressure, sweating, lacrimation, skin conductance, lower oesophageal contractility, and isolated forearm technique. New tools are EEG, bispectral index (BIS), and evoked potentials. BIS is a reliable indicator of the level of consciousness. It improves operating room use and reduces costs (by allowing faster patient turnover and reducing the use of drugs). BIS is presented as a numerical index ranging from 100 (awake) to 0 (isoelectric EEG). Values below 60 imply that the patient is almost certainly unconscious. There are no agreed standards against which any technique to measure the depth of anaesthesia can be judged. However, any monitor to measure depth of anaesthesia must provide sufficient information to enable satisfactory general anaesthesia to be produced during surgery. [Copyright &y& Elsevier]

The Bcl-2 family protein, Mcl-1 is known to have anti-apoptotic functions, and depletion of Mcl-1 by cellular stresses favors the apoptotic process. Moreover, Mcl-1 levels are frequently increased in various cancer cells, including non-small cell lung cancer (NSCLC), and is implicated in resistance to conventional chemotherapy and in cancer metastasis. In this study, we demonstrated that KRIBB11 accelerates the proteasomal degradation of Mcl-1 in the NSCLC cell line, A549. While KRIBB11 is an inhibitor of HSF1, we found that KRIBB11 induced Mcl-1 degradation in an HSF1-independent manner. Furthermore, this process was triggered via increase ubiquitination by the E3 ligase, Mule, rather than via de-ubiquitination by USP9X. Additionally, we found that Mcl-1 levels were only transiently reduced by KRIBB11: Mcl-1 levels were gradually restored as KRIBB11 activity diminished. However, we found that this effect was blocked in BIS (Bcl-2 interacting cell death suppressor, also called BAG3)-depleted cells, and that BIS prevents Mcl-1 from undergoing HSP70-driven proteasomal degradation, through an interaction with HSP70. Taken together, our results suggest that targeting Mcl-1 with KRIBB11 treatment, while simultaneously downregulating BIS, could be a therapeutic strategy in NSCLC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Out-of-hospital cardiac arrest (OHCA) is associated with significant mortality or may have a poor neurological outcome. Various community-training programmes have improved practices like bystander cardiopulmonary resuscitation (CPR) and early defibrillation using automated external defibrillator (AED). Post-resuscitation care has also changed significantly in the millennium. Interventions like targeted temperature management (TTM), avoidance of hyperoxia and emergency cardiac catheterisation have given patients a chance of a better neurological outcome. Despite these timely interventions, it is still very difficult to predict neurological outcome. The European Resuscitation Council and European Society of Intensive Care Medicine (ERC-ESICM) published guidance in 2015 with a strong recommendation to delay prognostication for at least 72 h and with an emphasis to adapt a multimodal approach, which includes neurological examination, biomarkers, electroencephalogram (EEG) and radiological tests. These interventions not only have cost attached to them, but the unpredictability has a significant emotional impact on family members. Bispectral index (BIS) monitoring device acts on the principle of EEG and converts the waveform into an absolute number and also measures the burst suppression. We hypothesize that patients who have a low BIS value and high burst suppression within 24 h of presentation will have a poor neurological outcome. The primary objective of this review is to look at BIS monitor as a tool, which could help bring forward the timing of prognostication., Methods: Electronic databases will be systematically searched for randomised controlled trials and prospective or retrospective cohort studies with no language restrictions. The search will be supplemented with grey literature searches of thesis, dissertations and hand searching of relevant journals. Two independent reviewers will screen, select and perform analysis according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) method. The selected studies will be analysed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system. Meta-analysis will be performed if suitable., Discussion: This review will synthesize the evidence on the use of BIS monitors within 24 h of achieving return of spontaneous circulation (ROSC) and may help in early prognostication., Systematic Review Registration: PROSPERO CRD 42016050224 .

Study Objective: To determine the efficacy of 2 different doses (150-300mg) of preoperative pregabalin on propofol and remifentanil doses for total intravenous anesthesia in laparoscopic cholecystectomy., Design: Prospective, randomized, placebo-controlled, double-blinded study., Setting: Training and research hospital., Patients: Forty-eight adult, American Society of Anesthesiologists physical status 1 and 2 patients., Interventions: Patients were randomly assigned to 3 groups to receive orally 1hour before surgery, a placebo group (group 1), pregabalin 150mg (group 2), or pregabalin 300mg (group 3)., Measurements: In the operating room, heart rate, systolic and diastolic blood pressures, SpO 2 , bispectral index, and body temperature were recorded just before anesthesia induction; 1 and 5minutes after induction; and at minutes 10, 15, 20, 25, 30, 35, and 40 of the surgery. Required propofol and remifentanil doses to obtain bispectral index value less than 60 were also recorded., Main Results: The remifentanil doses used in the pregabalin groups at minutes 10, 15, 20, 25, and 30 and propofol doses at minutes 15, 20, 25, and 30 were statistically significantly lower in comparison to the placebo group., Conclusion: The observations provide preliminary evidence that preoperative pregabalin may decrease anesthetic agent requirement in total intravenous anesthesia patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: It was hypothesized that monitoring end-tidal sevoflurane (ETS) during endoscopic surgery could reduce the incidence of intraoperative awareness in patients undergoing general anesthesia. Herein, the incidence of intraoperative awareness and other correlative factors was recorded and compared., Methods: Two thousand five hundred ASA I-III patients aged 18-80 years who underwent general anesthesia were randomly divided into 2 groups (n = 1250): routine care group (R) and ETS concentration group (E). ETS concentration was monitored in group E and maintained at a sevoflurane minimum alveolar concentration (MAC) of 0.7-1.3; group R was monitored using routine care, and the sevoflurane was maintained. Patients were assessed for intraoperative awareness with a questionnaire on their explicit memory 24-48 h after surgery., Results: A total of 2532 patients were selected, and 86 patients were excluded. As for the groups, 1219 patients were assigned to group E, and 1227 patients were assigned to group R. As for intraoperative awareness, group E had 2 patients, and group R had 14. Compared with group R, the incidence of intraoperative awareness in group E was significantly lower (p = 0.003); the time-averaged ETS concentration and sevoflurane dosage were lower in group E (p < 0.05); and no significant changes were found in tracheal extubation time, intravenous general anesthetic dosage, or postoperative complication incidence in either group (p > 0.05). The incidence of intraoperative awareness was higher in women than men in group R (p < 0.05)., Conclusion: Using ETS-guided anesthesia and maintaining the sevoflurane concentration (0.7-1.3 MAC) can decrease the incidence of patient awareness during endoscopic surgery., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Heat shock factor 1 (HSF1), a transcription factor activated by various stressors, regulates proliferation and apoptosis by inducing expression of target genes, such as heat shock proteins and Bcl-2 (B-cell lymphoma 2) interacting cell death suppressor (BIS). HSF1 also directly interacts with BIS, although it is still unclear whether this interaction is critical in the regulation of glioblastoma stem cells (GSCs). In this study, we examined whether small interfering RNA-mediated BIS knockdown decreased protein levels of HSF1 and subsequent nuclear localization under GSC-like sphere (SP)-forming conditions. Consistent with BIS depletion, HSF1 knockdown also reduced sex determining region Y (SRY)-box 2 (SOX2) expression, a marker of stemness, accompanying the decrease in SP-forming ability and matrix metalloprotease 2 (MMP2) activity. When HSF1 or BIS knockdown was combined with temozolomide (TMZ) treatment, a standard drug used in glioblastoma therapy, apoptosis increased, as measured by an increase in poly (ADP-ribose) polymerase (PARP) cleavage, whereas cancer stem-like properties, such as colony-forming activity and SOX2 protein expression, decreased. Taken together, our findings suggest that targeting BIS or HSF1 could be a viable therapeutic strategy for GSCs resistant to conventional TMZ treatment.

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of partial or complete collapse of the pharynx that result in a decrease in oxyhemoglobin saturation. Nasofibrolaryngoscopy under induced sleep is a promising alternative for identifying sites of upper airway obstruction in patients with OSA. This study aimed to compare the obstruction sites screened by drug-induced sleep endoscopy (DISE) using the Nose oropharynx hypopharynx and larynx (NOHL) and Velum oropharynx tongue base epiglottis (VOTE) classifications. We also determined the relationship between OSA severity and the number of obstruction sites and compared the minimum SaO 2 levels between DISE and polysomnography (PSG). This was a prospective study in 45 patients with moderate and severe OSA using DISE with target-controlled infusion of propofol bispectral index (BIS) monitoring. The retropalatal region was the most frequent obstruction site, followed by the retrolingual region. Forty-two percent of patients had obstruction in the epiglottis. Concentrically shaped obstructions were more prevalent in both ratings. The relationship between OSA severity and number of obstruction sites was significant for the VOTE classification. Similar minimum SaO 2 values were observed in DISE and PSG. The VOTE classification was more comprehensive in the analysis of the epiglottis and pharynx by DISE and the relationship between OSA severity and number of affected sites was also established by VOTE. The use of BIS associated with DISE is a reliable tool for the assessment of OSA patients.

This paper presents a new fault detection system in hypnotic sensors used for general anesthesia during surgery. Drug infusion during surgery is based on information received from patient monitoring devices; accordingly, faults in sensor devices can put patient safety at risk. Our research offers a solution to cope with these undesirable scenarios. We focus on the anesthesia process using intravenous propofol as the hypnotic drug and employing a Bispectral Index (BIS TM ) monitor to estimate the patient's unconsciousness level. The method developed identifies BIS episodes affected by disturbances during surgery with null clinical value. Thus, the clinician-or the automatic controller-will not take those measures into account to calculate the drug dose. Our method compares the measured BIS signal with expected behavior predicted by the propofol dose provider and the electromyogram (EMG) signal. For the prediction of the BIS signal, a model based on a hybrid intelligent system architecture has been created. The model uses clustering combined with regression techniques. To validate its accuracy, a dataset taken during surgeries with general anesthesia was used. The proposed fault detection method for BIS sensor measures has also been verified using data from real cases. The obtained results prove the method's effectiveness., Competing Interests: The authors declare no conflict of interest.

Purpose: With improved survivorship, the prevalence of breast cancer-related lymphedema (BCRL) continues to increase, leading to impairment of a patients' quality of life. While traditional diagnostic methods are limited by an inability to detect BCRL until clinically apparent, bioimpedance spectroscopy (BIS) has been shown to detect subclinical BCRL. The purpose of this study is to evaluate the role of BIS in the early detection of BCRL, as well as assessment of response to BCRL treatment., Methods: A retrospective review of 1,133 patients treated between November 2008 and July 2013 at two surgical practices was performed. Eligible patients (n = 326) underwent preoperative and postoperative L-Dex measurements. Patients were identified as having subclinical lymphedema if they were asymptomatic and the L-Dex score increased >10 U above baseline and were monitored following treatment. Patients were stratified by lymph node dissection technique [sentinel lymph node biopsy (SLNB) vs. axillary lymph node dissection (ALND)] and receipt of BCRL treatment., Results: The average age of the cohort was 56.2 years old, and mean follow-up was 21.7 months. Of the 326 patients, 210 underwent SLNB and 116 underwent ALND. BCRL was identified by L-Dex in 40 patients (12.3%). The cumulative incidence rate of subclinical lymphedema was 4.3% for SLNB (n = 9) and 26.7% for ALND (n = 31). Of those diagnosed with BCRL, 50% resolved following treatment, 27.5% underwent treatment without resolution, and 22.5% had resolution without treatment. The prevalence of persistent, clinical BCRL was 0.5% for SLNB and 8.6% for ALND., Conclusion: This study demonstrates both the feasibility and clinical utility of implementing L-Dex measurements in routine breast cancer care. L-Dex identified patients with possible subclinical BCRL and allowed for assessment of response to therapy.

Purpose: Drug-induced sedation endoscopy (DISE) and simulated snoring (SimS) can locate the site of obstruction in patients with sleep-disordered breathing (SDB). There is clinical evidence for a change in collapsibility of the upper airway depending on the depth of sedation. So far, a dose-response relationship between sedation and collapsibility has not been demonstrated., Methods: DISE and SimS were performed in 60 consecutive patients with SDB under monitoring of depth of sedation by BiSpectral Index® (BIS). Initially, SimS was conducted followed by DISE using bolus application of propofol. Sedation was performed up to a sedation level representing slow wave sleep (BIS = 40). The collapsibility of the upper airway was documented at decreasing sedation levels by an identical pictogram classification., Results: For all levels and patterns of obstruction, a dose-dependent increase in the collapsibility of the upper airway was detected. A maximum collapsibility was achieved at sedation levels representing slow wave sleep. The collapsibility during SimS corresponded to light sleep stages and did not cover slow wave sleep., Conclusion: A dose-dependent change of patterns of obstructions can be observed during DISE under BIS monitoring indicating sedation depth. The obtained patterns of obstruction during DISE and SimS should thus be interpreted with regard to the sedation depth.