31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Teaching Systems Improvement to Early Medical Students: Strategies and Lessons Learned.

PurposeDespite increasing emphasis in medical school education on quality and systems improvement, many medical schools lack sufficient faculty with expertise to teach systems improvement. Using the pedagogical content knowledge framework, this study explores how faculty engage students in systems improvement work and faculty perceptions of the outcomes for the health system and students.MethodIn May-June 2017, the authors interviewed 12 of 13 invited faculty with experience in teaching and engaging first-year medical students in systems improvement work, the course of students' systems improvement work over time, the impact of students' projects on health systems, and students' learning and attitudes about systems improvement. The authors conducted qualitative analysis iteratively with data collection to sufficiency.ResultsSix emergent themes characterized faculty's approach to guiding students in systems improvement work: faculty-student relationship, faculty role, student role, faculty-student shared responsibility for projects, faculty and student content knowledge, and project outcomes. The faculty-student relationship was foundational for successful systems improvement work. Faculty roles included project selection, project management, and health systems interactions. Students engaged in systems improvement as their faculty leveraged their knowledge and skills and created meaningful student roles. Faculty and students shared responsibility and colearned systems improvement content knowledge. Faculty defined successful outcomes as students' learning about the systems improvement process and interprofessional collaboration.ConclusionsFindings highlight the critical importance of pedagogical content knowledge to engage early learners in systems improvement work, understand their learning interests and needs, and manage their projects longitudinally

Anesthetic Considerations for Patients on Psychotropic Drug Therapies

Psychotropic drugs are used in the treatment of psychiatric and non-psychiatric conditions. Many patients who are on psychotropic medications may present for procedures requiring anesthesia. Psychotropic medications can have dangerous interactions with drugs commonly used in anesthesia, some of which can be life-threatening. In this review, we describe the current anesthetic considerations for patients on psychotropic drug therapies, including antidepressants, antipsychotics, mood stabilizers, anxiolytics, and stimulants. The pharmacology, side effects, and potential drug interactions of the commonly prescribed psychotropic drug therapies with anesthetic agents are described. Further, we highlight the current recommendations regarding the cessation and continuation of these medications during the perioperative period

Improved analgesia and reduced post-operative nausea and vomiting after implementation of an enhanced recovery after surgery (ERAS) pathway for total mastectomy

Abstract Background Enhanced Recovery After Surgery (ERAS) pathways have been shown in multiple surgical disciplines to improve outcomes, including reduced opioid consumption, length of stay, and post-operative nausea and vomiting (PONV). However, very few studies describe the application of ERAS to breast surgery and even fewer describe ERAS for outpatient surgery. We describe the implementation and efficacy of an Enhanced Recovery After Surgery (ERAS) pathway for total skin-sparing mastectomy with immediate reconstruction in an outpatient setting. Methods We implemented an evidence-based, multimodal ERAS pathway for all patients undergoing total skin-sparing mastectomy surgery with immediate reconstruction at a single 23-h stay surgery center. Highlights of the ERAS pathway included: preoperative acetaminophen, gabapentin, and scopolamine; regional anesthesia for the breast (Pectoral blocks type 1 and 2 or paravertebral block); and intraoperative dexamethasone and ondansetron. This retrospective study included all American Society of Anesthesiology (ASA) Class 1–3 patients undergoing total skin-sparing mastectomy surgery with immediate reconstruction between July 2013 and April 2016. We compared 96 patients who were in the ERAS pathway (ERAS group) to a retrospective cohort of 276 patients (Pre group). The primary outcome was total perioperative opioid consumption. Secondary outcomes were highest postoperative pain scores, incidence of PONV, and length of stay. Results Patients in the ERAS group had significantly lower total perioperative opioid consumption compared to the Pre group (mean (SD): 111.4 mg (46.0) vs. 163.8 mg (73.2) oral morphine equivalents, p < 0.001). Patients in the ERAS group also had a lower incidence of PONV (28% vs. 50%, p < 0.001). Patients in the ERAS group reported less pain in the recovery room, with a two-point decrease in highest pain score (median [interquartile range (IQR)]: 4 [2,6] in ERAS group vs. 6 [4,7] in Pre group, p < 0.001). There was no clinically significant difference in length of stay (median [IQR]: 1144 min [992, 1259] in ERAS group vs. 1188 [1058, 1344] in Pre group, p = 0.006). Conclusion Implementation of an ERAS pathway for total skin-sparing mastectomy with reconstruction that incorporates regional anesthesia is feasible in a 23-h-stay hospital. Patients in the ERAS pathway had improved post-operative analgesia and reduced post-operative nausea and vomiting

Extraplexus versus intraplexus ultrasound-guided interscalene brachial plexus block for ambulatory arthroscopic shoulder surgery: A randomized controlled trial.

BackgroundThis randomized study compared the efficacy and safety of extraplexus and intraplexus injection of local anesthetic for interscalene brachial plexus block.Methods208 ASA I-II patients scheduled for elective shoulder arthroscopy under general anesthesia and ultrasound-guided interscalene brachial plexus block were randomly allocated to receive an injection of 25mL ropivacaine 0.5% either between C5-C6 nerve roots (intraplexus), or anterior and posterior to the brachial plexus into the plane between the perineural sheath and scalene muscles (extraplexus). The primary outcome was time to loss of shoulder abduction. Secondary outcomes included block duration, perioperative opioid consumption, pain scores, block performance time, number of needle passes, onset of sensory blockade, paresthesia, recovery room length of stay, patient satisfaction, incidence of Horner's syndrome, dyspnea, hoarseness, and post-operative nausea and vomiting.ResultsTime to loss of shoulder abduction was faster in the intraplexus group (log-rank p-value&lt;0.0005; median [interquartile range]: 4 min [2-6] vs. 6 min [4-10]; p-value &lt;0.0005). Although the intraplexus group required fewer needle passes (2 vs. 3, p&lt;0.0005), it resulted in more transient paresthesia (35.9% vs. 14.5%, p = 0.0004) with no difference in any other secondary outcome.ConclusionThe intraplexus approach to the interscalene brachial plexus block results in a faster onset of motor block, as well as sensory block. Both intraplexus and extraplexus approaches to interscalene brachial plexus block provide effective analgesia. Given the increased incidence of paresthesia with an intraplexus approach, an extraplexus approach to interscalene brachial plexus block is likely a more appropriate choice

Extraplexus versus intraplexus ultrasound-guided interscalene brachial plexus block for ambulatory arthroscopic shoulder surgery: A randomized controlled trial.

BackgroundThis randomized study compared the efficacy and safety of extraplexus and intraplexus injection of local anesthetic for interscalene brachial plexus block.Methods208 ASA I-II patients scheduled for elective shoulder arthroscopy under general anesthesia and ultrasound-guided interscalene brachial plexus block were randomly allocated to receive an injection of 25mL ropivacaine 0.5% either between C5-C6 nerve roots (intraplexus), or anterior and posterior to the brachial plexus into the plane between the perineural sheath and scalene muscles (extraplexus). The primary outcome was time to loss of shoulder abduction. Secondary outcomes included block duration, perioperative opioid consumption, pain scores, block performance time, number of needle passes, onset of sensory blockade, paresthesia, recovery room length of stay, patient satisfaction, incidence of Horner's syndrome, dyspnea, hoarseness, and post-operative nausea and vomiting.ResultsTime to loss of shoulder abduction was faster in the intraplexus group (log-rank p-valueConclusionThe intraplexus approach to the interscalene brachial plexus block results in a faster onset of motor block, as well as sensory block. Both intraplexus and extraplexus approaches to interscalene brachial plexus block provide effective analgesia. Given the increased incidence of paresthesia with an intraplexus approach, an extraplexus approach to interscalene brachial plexus block is likely a more appropriate choice