A randomized controlled trial comparing three supraglottic airway devices used as a conduit to facilitate tracheal intubation with flexible bronchoscopy.

PURPOSE: Once difficult ventilation and intubation are declared, guidelines suggest the use of a supraglottic airway (SGA) as a rescue device to ventilate and, if oxygenation is restored, subsequently as an intubation conduit. Nevertheless, few trials have formally studied recent SGA devices in patients. Our objective was to compare the efficacy of three second-generation SGA devices as conduits for bronchoscopy-guided endotracheal intubation. METHODS: In this prospective, single-blinded three-arm randomized controlled trial, patients with an American Society of Anesthesiologists Physical Status of I-III undergoing general anesthesia were randomized to bronchoscopy-guided endotracheal intubation using AuraGain™, Air-Q® Blocker, or i-gel® devices. We excluded patients with contraindications to an SGA or drugs and who were pregnant or had a neck, spine, or respiratory anomaly. The primary outcome was intubation time, measured from SGA circuit disconnection to CO2 measurement. Secondary outcomes included ease, time, and success of SGA insertion; success of intubation on first attempt; overall intubation success; number of attempts to intubate; ease of intubation; and ease of SGA removals. RESULTS: One hundred and fifty patients were enrolled from March 2017 to January 2018. Median intubation times were similar across the three groups (Air-Q Blocker, 44 sec; AuraGain, 45 sec; i-gel, 36 sec; P = 0.08). The i-gel was faster to insert (i-gel: 10 sec; Air-Q Blocker, 16 sec; AuraGain, 16 sec; P < 0.001) and easier to insert (Air-Q Blocker vs i-gel, P = 0.001; AuraGain vs i-gel, P = 0.002). Success of SGA insertion, success of intubation, and number of attempts were similar. The Air-Q Blocker was easier to remove than the i-gel (P < 0.001). CONCLUSION: All three second-generation SGA devices performed similarly regarding intubation. Despite minor benefits of the i-gel, clinicians should select their SGA based on clinical experience. STUDY REGISTRATION: ClinicalTrials.gov (NCT02975466); registered on 29 November 2016.

RéSUMé: OBJECTIF: Une fois qu'une ventilation et une intubation difficiles sont déclarées, les lignes directrices préconisent le recours à un dispositif supraglottique comme modalité de sauvetage pour ventiler le patient et, si l'oxygénation est rétablie, être ensuite utilisé comme conduit d'intubation. Toutefois, peu d'études ont formellement analysé l'utilisation des dispositifs supraglottiques récents chez de véritbales patients. Notre objectif était de comparer l'efficacité de trois dispositifs supraglottiques de deuxième génération utilisés comme conduits pour l'intubation endotrachéale guidée par bronchoscopie. MéTHODE: Dans cette étude prospective randomisée contrôlée à trois bras et à simple insu, les patients de statut physique I-III selon l'American Society of Anesthesiologists bénéficiant d'une anesthésie générale ont été randomisés à recevoir une intubation endotrachéale guidée par bronchoscopie via les dispositifs AuraGain™, Air-Q® Blocker ou i-gel®. Nous avons exclu les patients présentant des contre-indications à l'utilisation d'un dispositif supraglottique ou aux médicaments, ainsi que les patientes enceintes et les patients présentant une anomalie au niveau du cou, de la colonne vertébrale ou des voies aériennes. Le critère d'évaluation principal était le temps d'intubation mesuré entre le moment de déconnexion du dispositif supraglottique du circuit et le moment de mesure du CO2. Les critères d'évaluation secondaires comprenaient la facilité, le délai et la réussite de l'insertion du dispositif supraglottique; la réussite de l'intubation à la première tentative; la réussite globale de l'intubation; le nombre de tentatives d'intubation; la facilité d'intubation; et la facilité de retrait du dispositif supraglottique. RéSULTATS: Cent cinquante patients ont été recrutés de mars 2017 à janvier 2018. Les délais d'intubation médians étaient similaires dans les trois groupes (Air-Q Blocker : 44 sec; AuraGain : 45 sec; i-gel : 36 sec; P = 0,08). L'i-gel était plus rapide à insérer (i-gel : 10 sec; Air-Q Blocker : 16 sec; AuraGain : 16 sec; P < 0,001) et plus facile à insérer (Air-Q Blocker vs i-gel : P = 0,001; AuraGain vs i-gel : P = 0,002). La réussite de l'insertion du dispositif supraglottique, la réussite de l'intubation et le nombre de tentatives étaient similaires. L'Air-Q Blocker était plus facile à retirer que l'i-gel (P < 0,001). CONCLUSION: Les trois dispositifs supraglottiques de deuxième génération ont tous affiché une performance similaire en matière d'intubation. Malgré des avantages mineurs de l'i-gel, les cliniciens devraient choisir leur dispositif supraglottique en fonction de leur expérience clinique. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT02975466); enregistrée le 29 novembre 2016.

Chronic pain patients' willingness to share personal identifiers on the web for the linkage of medico-administrative claims and patient-reported data: The chronic pain treatment cohort.

PURPOSE: The linkage between patient-reported data and medico-administrative claims is of great interest for epidemiologic research. The goal of this study was to assess the willingness of people living with chronic pain to share personal identifiers on the web for the linkage of medico-administrative and patient-reported data. METHODS: This methodological investigation was achieved in the context of the implementation of the chronic pain treatment (COPE) cohort. A web-based recruitment initiative targeting adults living with chronic pain was conducted in the province of Quebec (Canada). RESULTS: A total of 1935 participants completed the questionnaire (mean age: 49.86 ± 13.27; females: 83.69%), 921 (47.60%) of which agreed to data linkage and shared their personal identifiers (name, date of birth, health insurance number online). The most common reasons for refusal were: (1) concerns regarding data security/privacy (25.71%) and (2) the belief that the requested data were too personal/intrusive (13.52%). Some participants did not understand the relevance of data linkage (11.81%). Participants from the COPE cohort and those from the subsample who agreed to data linkage were comparable to other random samples of chronic pain individuals in terms of age and pain characteristics. CONCLUSIONS: Although approximately half of the participants refused data linkage, our approach allowed for the implementation of a data platform that contains a diverse and substantial sample. This investigation has also led to the formulation of recommendations for web-based data linkage, including placing items designed to assess willingness to share personal identifiers at the end of the questionnaire, adding explanatory videos, and using a mixed-mode questionnaire.

The effects of lidocaine spray and intracuff alkalinized lidocaine on the occurrence of cough at extubation: a double-blind randomized controlled trial.

PURPOSE: Our study aimed to evaluate the effects of lidocaine sprayed onto the larynx and/or injected into the tracheal tube cuff to decrease the incidence of cough at extubation and postoperative sore throat. METHODS: One hundred twenty women scheduled for gynecological surgery < 120 min in duration were enrolled in this randomized double-blind prospective study. Prior to tracheal intubation, 4% lidocaine or 0.9% saline was sprayed onto the patients' supra- and subglottic areas. After tracheal intubation, the tracheal tube cuff was filled with either an alkalinized 2% lidocaine solution or 0.9% saline. This resulted in four groups: spray-cuff, spray-saline, saline-cuff, and saline-saline. A logistic regression comprising the two factors was used for analysis. The primary outcome was the incidence of cough at extubation. The secondary outcome was the incidence and severity of sore throat reported by patients at 15 min, 60 min, and 24 hr after tracheal extubation. RESULTS: Cough occurred in 42%, 24%, 63%, and 69% of patients in the spray-cuff, spray-saline, saline-cuff, and saline-saline groups, respectively. The use of lidocaine spray decreased the incidence of cough at extubation (odds ratio = 0.256; 95% confidence interval 0.118 to 0.554; P < 0.001); however, the use of intracuff alkalinized lidocaine had no impact on the occurrence of cough (P = 0.471). Severity of sore throat was clinically low (visual analog scale [VAS] ≤ 3) in all groups. No significant difference was observed in hoarseness, dysphagia, nausea, or vomiting. CONCLUSION: Sprayed lidocaine decreases the incidence of cough at tracheal extubation in surgeries of less than two hours. The use of alkalinized lidocaine into high-volume/low-pressure endotracheal cuffs had no impact on decreasing the incidence of cough or pain.

Preoperative pregabalin does not reduce propofol ED(50): a randomized controlled trial.

BACKGROUND: In many studies, gabapentinoids, such as pregabalin, have been shown to reduce preoperative anxiety. This anxiolysis is often accompanied by sedation, one of the most frequent side effects of pregabalin. We hypothesized that pregabalin taken preoperatively could reduce propofol requirements for induction of general anesthesia. METHODS: A randomized double-blind placebo-controlled trial was conducted after approval by the local ethics committee. Fifty women aged 18-40 yr, American Anesthesiologists Society physical status I and II, and scheduled to undergo elective laparoscopic gynecologic procedures were enrolled after written consent. Treatment group patients were given pregabalin 150 mg po one hour before surgery while patients in the control group received a placebo. The primary outcome was the propofol dose required to achieve a targeted anesthetic depth in 50% of the population, i.e., effective dose (ED)50. The ED50 was estimated using Dixon's up-and-down methodology. The targeted anesthetic depth was defined based on predetermined entropy monitoring values (State Entropy [SE] < 50 and Response Entropy [RE]-SE < 10). As a secondary outcome, we tested if pregabalin reduced pre-induction anxiety levels which were measured on a 0-100 scale. RESULTS: The propofol ED50 was not statistically different between the pregabalin group (mean 1.33 mg·kg(-1); 95% confidence interval [CI] 1.23 to 1.43) vs the placebo group (mean 1.37 mg·kg(-1); 95% CI 1.28 to 1.46); P = 0.19. Also, pre-induction anxiety level was not different between groups (median 31; interquartile range [IQR] [10-52] vs median 42; IQR [4-71], respectively; P = 0.41). CONCLUSIONS: Preoperative pregabalin does not reduce propofol requirements in a population of healthy young women undergoing laparoscopic gynecologic procedures. This study failed to show a pre-induction anxiolytic effect of pregabalin in such a population. This trial was registered at www.clinicaltrials.gov (NCT01158859).

Akt and XIAP regulate the sensitivity of human uterine cancer cells to cisplatin, doxorubicin and taxol.

We have investigated the interrelationship between two anti-apoptotic factors, XIAP and Akt, and their role in chemoresistance of uterine cancer cells. We used one cervical cancer cell line (HeLa) and two endometrial cancer cell lines (KLE and Ishikawa) as a model. The three drugs decreased Akt and XIAP content and induced apoptosis in P-Akt-negative HeLa cells. In P-Akt1/3-positive Ishikawa cells apoptosis induction correlated with XIAP decrease. P-Akt1/2/3-positive KLE cells showed maximum chemoresistance as XIAP and Akt levels/phosphorylation remained stable in response to the three drugs, and only cisplatin could significantly induce apoptosis. We found that XIAP and Akt were functionally linked in uterine cancer cells, as downregulation of XIAP with RNAi decreased P-Akt levels, and inhibition of PI3-K/Akt activity using LY294002 decreased XIAP content. Overexpression of constitutively active Akt isoforms in HeLa cells induced isoform-specific sensitivity to doxorubicin and taxol but not cisplatin. XIAP RNAi increased the cell-specific sensitivity to cisplatin and doxorubicin but not taxol. Finally, we found P-Akt immunoreactivity in epithelial cells from multiple human endometrial carcinoma tumors, suggesting that Akt may also regulate chemosensitivity in uterine cancers in vivo. Altogether these results highlight an intertwined role for specific Akt isoforms and XIAP in chemoresistance of uterine cancer cells.

Biological evaluation of novel estrogen-platinum(II) hybrid molecules on uterine and ovarian cancers-molecular modeling studies.

We have recently reported the synthesis of a series of original 17beta-estradiol-linked platinum(II) hybrid molecules. The biological activity of these compounds was evaluated in vitro on estrogen dependent and independent (ER(+) and ER(-)) human uterine and ovarian cancers. The hybrid molecules present higher affinity than that of 17beta-estradiol for the estrogen receptor alpha (ERalpha). The cytotoxicity and the affinity of the hybrid molecules are explained using molecular modeling analysis. This study further confirms that the derivatives made of a 2-(2'-aminoethyl)pyridine ligand displayed superior activity against the cell lines particularly when the connecting arm is 8-10 carbon atoms long. Molecular modeling shows that a long side chain can facilitate the access of the platinum(II) moiety to DNA. The novel compounds also prove to be moderately cytotoxic against platinum resistant endometrial and ovarian cancer cell lines.

AKT involvement in cisplatin chemoresistance of human uterine cancer cells.

OBJECTIVE: The aim of this study was to investigate the possible involvement of Akt activity and specific isoforms (Akt1, Akt2, and Akt3) in the resistance of human uterine cancer cells to cisplatin. METHODS: Two different endometrial (HEC-1-A and KLE) and one cervical (HeLa) cancer cell lines all known as wild-type PTEN (tumor suppressor phosphatase tensin homologue, a lipid phosphatase involved in the negative regulation of Akt activity) were used for these studies. RESULTS: Basal levels of Akt1, Akt2, and Akt3 mRNAs were determined by real-time quantitative RT-PCR studies and Western blot analyses were carried out to determine protein abundance of each isoforms. Akt1 mRNA and protein were present in all cell lines studied. Akt2 and Akt3 mRNAs and proteins were strongly expressed in KLE cells. Surprisingly, Akt phosphorylation was found in KLE expressing high levels of wild-type PTEN protein. KLE cells remained resistant to PI 3-K inhibitor, indicating that Akt phosphorylation might be, in part, independent of PI 3-K in this cell line. Cisplatin induced apoptosis in HeLa and HEC-1-A cells, but KLE cells expressing Akt2 and Akt3 remained more resistant to cisplatin. Knockout of Akt isoforms using specific siRNA technology increased the sensitivity of KLE cells toward cisplatin and caused a significant induction of cell death. CONCLUSION: Taken together, these results suggest that specific Akt isoforms such as Akt2 and Akt3 might be involved in chemoresistance to cisplatin and that these isoforms could be putative targets for gene therapy in uterine cancers.

Akt regulates COX-2 mRNA and protein expression in mutated-PTEN human endometrial cancer cells.

In human endometrial cancer, the fourth most common cancer in women, tumor suppressor phosphatase tensin homologue (PTEN) is frequently mutated. In the presence of a mutated PTEN protein, Akt phosphorylation levels are increased leading to the activation of this survival pathway. Numerous studies indicated that COX-2 is inappropriately induced and up-regulated in a number of malignant cancer cells. COX-2 plays an important role in tumor cell biology, taking part actively in angiogenesis particularly via the production of prostaglandin E2 (PGE2). The present study was undertaken to determine the involvement of PI 3-K/Akt pathway in the regulation of COXs expression and PGE2 synthesis. Three different human endometrial cancer cell lines known to have wild-type PTEN (HEC 1-A) or a mutated inactive PTEN protein (RL 95-2 and Ishikawa) were used for these studies. Results showed that Akt phosphorylation was high in mutated PTEN cells. RT-PCR studies revealed that Akt1 and Akt2 were the regulated forms whereas Akt3 mRNA was nearly undetectable. COX-2 mRNA expression and protein levels were high in these cells compared to wild-type PTEN cells as demonstrated by RT-PCR and Western analysis respectively. PGE2 production was higher in mutated-PTEN expressing phospho-Akt and COX-2 compared to wild-type PTEN cells. Inhibition of PI 3-K with Wortmannin and LY294002 blocked Akt phosphorylation and inhibited expression of COX-2 in mutated-PTEN cells. Inhibition of Akt phosphorylation with specific PI 3-K inhibitors and down-regulation of COX-2 increased apoptosis in human endometrial cancer cells. Likewise, transfection of mutated-PTEN cells with a dominant negative Akt vector, resulted in COX-2 down-regulation and activation of apoptosis, as demonstrated by Hoechst nuclear staining. On the opposite, activation of Akt using a constitutively active expression vector, resulted in the up-regulation of COX-2 protein expression. Specific inhibition of COX-2 with NS-398 induced apoptosis in COX-2 expressing human endometrial cancer cells. It is concluded that the PI 3-K/Akt survival pathway is involved in the regulation of COX-2 and PGE2 synthesis in human endometrial cancer cells.

Regulation of COX-2 protein expression by Akt in endometrial cancer cells is mediated through NF-kappaB/IkappaB pathway.

BACKGROUND: Cyclooxygenase-2 (COX-2) has been shown to be highly expressed in a broad series of primary endometrial tumors and its expression may be closely associated with parameters of tumor aggressiveness. In human endometrial cancer, tumor suppressor phosphatase tensin homologue (PTEN) is frequently mutated. In the presence of a mutated PTEN protein, Akt phosphorylation levels increase leading to the activation of this survival pathway. The nuclear transcription factor kappaB (NF-kappaB) is a well establish regulator of genes encoding cytokines, cytokine receptors, and cell adhesion molecules that drive immune and inflammatory responses. More recently, NF-kappaB activation has been connected with multiple aspects of oncogenesis, including the control of apoptosis, cell cycle, differentiation, and cell migration. It is known that Akt may act through NF-kappaB pathway and that COX-2 gene has been shown to be regulated at the promoter level by NF-kappaB. Recently, we showed that Akt regulates COX-2 gene and protein expressions in phospho-Akt expressing endometrial cancer cells. The present study was undertaken to determine the involvement of NF-kappaB pathway and IkappaB (an inhibitor of NF-kappaB) in the regulation of COX-2 expression and to determine more precisely the downstream targets of Akt involved in this process. RESULTS: Three different human endometrial cancer cell lines known to have wild type PTEN (HEC 1-A) or a mutated inactive PTEN protein (RL 95-2 and Ishikawa) were used for these studies. Expression IkappaB and Phospho-IkappaB were evaluated by Western analysis. The presence of IkappaB phosphorylation was found in all cell lines studied. There was no difference between cell lines in term of NF-kappaB abundance. Inhibition of PI 3-K with Wortmannin and LY294002 blocked IkappaB phosphorylation, reduced NF-kappaB nuclear activity, reduced COX-2 expression and induced apoptosis. Transfection studies with a dominant negative Akt vector blocked IkappaB phosphorylation and reduced COX-2 expression. On the opposite, constitutively active Akt transfections resulted in the induction of IkappaB phosphorylation and up-regulation of COX-2. CONCLUSION: These results demonstrate that Akt signals through NF-kappaB/IkappaB pathway to induce COX-2 expression in mutated PTEN endometrial cancer cells.

Akt activity in endometrial cancer cells: regulation of cell survival through cIAP-1.

In a number of different cancer including endometrial cancers, tumor suppressor phosphatase tensin homologue (PTEN, a lipid phosphatase) is frequently mutated. PTEN dephosphorylates PI 3-K product, phosphatidylinositol 3,4,5-triphosphate (PIP3), into inactive PIP2 which blocks Akt activation/phosphorylation. In the present study, we have used an endometrial cancer cell line known to possess wild-type PTEN (HEC-1-A) and two mutated inactive PTEN protein cell lines (RL-95-2 and Ishikawa) to investigate importance of PI 3-K/PTEN/Akt survival pathway in endometrial cancers. As hypothesised, results showed high levels of Akt1/2 mRNAs and protein phosphorylation in the two mutated PTEN human endometrial cancer cells. To test the possible involvement of Akt in the regulation of survival factors, Bcl-2, XIAP, cIAP-1 and cIAP-2 expression were measured. cIAP-1 protein expression was high in cells expressing phospho-Akt. XIAP and cIAP-2 protein expression was not influenced by the presence of active Akt. Akt phosphorylation decreased and apoptosis was strongly increased in mutated PTEN human endometrial cancer cells in the presence of PI 3-K inhibitor (Wortmannin) which was accompanied by a down-regulation of cIAP-1 protein. Wortmannin had no effect on wild-type PTEN HEC-1-A cell line. Although, Bcl-2 expression was strongly expressed in mutated-PTEN cells, expression remained stable in the presence of Wortmannin suggesting that Bcl-2 is not regulated by Akt. Overexpression of Akt using a constitutively active Akt expression vector resulted in an up-regulation of cIAP-1 expression. These results suggest a pivotal role of Akt in the regulation of endometrial cancer cell survival through the up-regulation of a specific inhibitor of apoptosis protein.