Leadership during airway management in the intensive care unit: A video-reflexive ethnography study.

Effective leadership is crucial to team performance within the intensive care unit. This novel study aimed to explore how staff members from an intensive care unit conceptualize leadership and what facilitators and barriers to leadership exist within a simulated workplace. It also aimed to identify factors that intersect with their perceptions of leadership. This study was underpinned by interpretivism, and video-reflexive ethnography was chosen as the methodology for the study. The use of both video recording (to capture the complex interactions occurring in the ICU) and team reflexivity allowed repeated analysis of those interactions by the research team. Purposive sampling was used to recruit participants from an ICU in a large tertiary and private hospital in Australia. Simulation groups were designed to replicate the typical clinical teams involved in airway management within the intensive care unit. Twenty staff participated in the four simulation activities (five staff per simulation group). Each group simulated the intubations of three patients with hypoxia and respiratory distress due to severe COVID-19. All 20 participants who completed the study simulations were invited to attend video-reflexivity sessions with their respective group. Twelve of the 20 participants (60%) from the simulations took part in the reflexive sessions. Video-reflexivity sessions (142 min) were transcribed verbatim. Transcripts were then imported into NVivo software for analysis. The five stages of framework analysis were used to conduct thematic analysis of the video-reflexivity focus group sessions, including the development of a coding framework. All transcripts were coded in NVivo. NVivo queries were conducted to explore patterns in the coding. The following key themes regarding participants' conceptualizations of leadership within the intensive care were identified: (1) leadership is both a group/shared process and individualistic/hierarchical; (2) leadership is communication; and (3) gender is a key leadership dimension. Key facilitators identified were: (1) role allocation; (2) trust, respect and staff familiarity; and (3) the use of checklists. Key barriers identified were: (1) noise and (2) personal protective equipment. The impact of socio-materiality on leadership within the intensive care unit is also identified.

In vivo proton magnetic resonance spectroscopy of breast cancer: a review of the literature.

An emerging clinical modality called proton magnetic resonance spectroscopy ((1)H-MRS) enables the non-invasive in vivo assessment of tissue metabolism and is demonstrating applications in improving the specificity of MR breast lesion diagnosis and monitoring tumour responsiveness to neoadjuvant chemotherapies. Variations in the concentration of choline-based cellular metabolites, detectable with (1)H-MRS, have shown an association with malignant transformation of tissue in in vivo and in vitro studies. (1)H-MRS exists as an adjunct to the current routine clinical breast MR examination. This review serves as an introduction to the field of breast (1)H-MRS, discusses modern high-field strength and quantitative approaches and technical considerations, and reviews the literature with respect to the application of (1)H-MRS for breast cancer.

Confidence in airway management proficiency: a mixed methods study of intensive care specialists in Australia and New Zealand.

Objective: To explore self-confidence, and the respective facilitators and barriers, among intensive care specialists in Australia and New Zealand in relation to airway management. Design: A mixed methods study. Setting: 11 intensive care units across Australia and New Zealand. Participants: 48 intensive care specialists. Intervention: A structured online interview and the presentation of three discrete airway management clinical scenarios - routine endotracheal intubation, awake fibreoptic intubation (AFOI), and emergency front of neck access (FONA). Main outcome measures: Graded Likert scale responses regarding confidence in airway management were analysed, and perceptions of facilitators and barriers to confidence in each select scenario were obtained as free text. A deductive thematic analysis was done iteratively on free text entry and allowed for the development of a coding framework. NVivo software used the coding framework to run coding queries and cross-tabulations for comparison of relationships between themes and participant demographic characteristics. Results: Participants reported differing levels of confidence. Clinical experience, an anaesthetic qualification and training (including simulation) were the major facilitators to influencing confidence. Participants were more confident performing routine intubation than AFOI or FONA. Equipment, checklists or protocols, and availability of video-laryngoscopy were also identified as facilitators to confidence by most participants. Work relationships, teams and other staff availability were identified as further facilitators to confidence; lack of these factors were less commonly identified as barriers. Conclusions: Confidence in airway management among intensive care specialists in Australia and New Zealand varies, both between specialists and depending on clinical context. Multiple facilitators to improving this exist, including additional mandatory training.

The use of video laryngoscopy outside the operating room: A systematic review.

This study aimed to describe how video laryngoscopy is used outside the operating room within the hospital setting. Specifically, we aimed to summarise the evidence for the use of video laryngoscopy outside the operating room, and detail how it appears in current clinical practice guidelines. A literature search was conducted across two databases (MEDLINE and Embase), and all articles underwent screening for relevance to our aims and pre-determined exclusion criteria. Our results include 14 clinical practice guidelines, 12 interventional studies, 38 observational studies. Our results show that video laryngoscopy is likely to improve glottic view and decrease the incidence of oesophageal intubations; however, it remains unclear as to how this contributes to first-pass success, overall intubation success and clinical outcomes such as mortality outside the operating room. Furthermore, our results indicate that the appearance of video laryngoscopy in clinical practice guidelines has increased in recent years, and particularly through the COVID-19 pandemic. Current COVID-19 airway management guidelines unanimously introduce video laryngoscopy as a first-line (rather than rescue) device.

Immunosensitization with a Bcl-2 small molecule inhibitor.

Several tumor immunotherapy approaches result in a low percentage of durable responses in selected cancers. We hypothesized that the insensitivity of cancer cells to immunotherapy may be related to an anti-apoptotic cancer cell milieu, which could be pharmacologically reverted through the inhibition of antiapoptotic Bcl-2 family proteins in cancer cells. ABT-737, a small molecule inhibitor of the antiapoptotic proteins Bcl-2, Bcl-w and Bcl-x(L), was tested for the ability to increase antitumor immune responses in two tumor immunotherapy animal models. The addition of systemic therapy with ABT-737 to the immunization of BALB/c mice with tumor antigen peptide-pulsed dendritic cells (DC) resulted in a significant delay in CT26 murine colon carcinoma tumor growth and improvement in survival. However, the addition of ABT-737 to either a vaccine strategy involving priming with TRP-2 melanoma antigen peptide-pulsed DC and boosting with recombinant Listeria monocytogenes expressing the same melanoma antigen, or the adoptive transfer of TCR transgenic cells, did not result in superior antitumor activity against B16 murine melanoma. In vitro studies failed to demonstrate increased cytotoxic lytic activity when testing the combination of ABT-737 with lymphokine activated killer (LAK) cells, or the death receptor agonists Fas, TRAIL-ligand or TNF-alpha against the CT26 and B16 cell lines. In conclusion, the Bcl-2 inhibitor ABT-737 sensitized cancer cells to the antitumor effect of antigen-specific immunotherapy in a vaccine model for the CT26 colon carcinoma in vivo but not in two immunotherapy strategies against B16 melanoma.

Targeted therapies to improve tumor immunotherapy.

Durable tumor regression and potential cures of metastatic solid cancers can be achieved by a variety of cellular immunotherapy strategies, including cytokine therapy, dendritic cell-based vaccines, and immune-activating antibodies, when used in so-called immune-sensitive cancers such as melanoma and renal cell carcinoma. However, these immunotherapy strategies have very low tumor response rates, usually in the order of 5% to 10% of treated patients. We propose that the antitumor activity of adequately stimulated tumor antigen-specific T cells is limited by local factors within the tumor milieu and that pharmacologic modulation of this milieu may overcome tumor resistance to immunotherapy. By understanding the mechanisms of cancer cell immune escape, it may be possible to design rational combinatorial approaches of novel therapies able to target immunosuppressive or antiapoptotic molecules in an attempt to reverse resistance to immune system control. We term this mode of treatment "immunosensitization." Ideal candidates for immunosensitizing drugs would be targeted drugs that block key oncogenic mechanisms in cancer cells resulting in a proapoptotic cancer cell milieu and at the same time do not negatively interfere with critical lymphocyte functions.

Enhanced antitumor activity induced by adoptive T-cell transfer and adjunctive use of the histone deacetylase inhibitor LAQ824.

Tumors grow in the presence of antigen-specific T cells, suggesting the existence of intrinsic cancer cell escape mechanisms. We hypothesized that a histone deacetylase (HDAC) inhibitor could sensitize tumor cells to immunotherapy because this class of agents has been reported to increase tumor antigen expression and shift gene expression to a proapoptotic milieu in cancer cells. To test this question, we treated B16 murine melanoma with the combination of the HDAC inhibitor LAQ824 and the adoptive transfer of gp100 melanoma antigen-specific pmel-1 T cells. The combined therapy significantly improved antitumor activity through several mechanisms: (a) increase in MHC and tumor-associated antigen expression by tumor cells; (b) decrease in competing endogenous lymphocytes in recipient mice, resulting in a proliferative advantage for the adoptively transferred cells; and (c) improvement in the functional activity of the adoptively transferred lymphocytes. We confirmed the beneficial effects of this HDAC inhibitor as a sensitizer to immunotherapy in a different model of prophylactic prime-boost vaccination with the melanoma antigen tyrosinase-related protein 2, which also showed a significant improvement in antitumor activity against B16 melanoma. In conclusion, the HDAC inhibitor LAQ824 significantly enhances tumor immunotherapy through effects on target tumor cells as well as improving the antitumor activity of tumor antigen-specific lymphocytes.