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ciency is needed. Effective reforms should improve inputs, outputs but also efficiency.The Accreditation Council for Graduate Medical Education has shifted to competency-based medical education. This educational framework requires the description of educational outcomes based on the knowledge, skills and behaviors expected of competent trainees. It also requires an assessment program to provide formative feedback to trainees as they progress to competency in each outcome. Critical to the success of a curriculum is its practical implementation. This article describes the development of model curricula for anesthesiology residency training in regional anesthesia and acute pain medicine (core and advanced) using a competency-based framework. We further describe how the curricula were distributed through a shared web-based platform and mobile application.Local anesthetics (LAs) are commonly infiltrated into surgical wounds for postsurgical analgesia. While many adjuncts to LA agents have been studied, it is unclear which adjuncts are most effective for co-infiltration to improve and prolong analgesia. We performed a systematic review on adjuncts (excluding epinephrine) to local infiltrative anesthesia to determine their analgesic efficacy and opioid-sparing properties. Multiple databases were searched up to December 2019 for randomized controlled trials (RCTs) and two reviewers independently performed title/abstract screening and full-text review. Inclusion criteria were (1) adult surgical patients and (2) adjunct and LA agents infiltration into the surgical wound or subcutaneous tissue for postoperative analgesia. To focus on wound infiltration, studies on intra-articular, peri-tonsillar, or fascial plane infiltration were excluded. The primary outcome was reduction in postoperative opioid requirement. Secondary outcomes were time-to-first analgesic use, postoperative pain score, and any reported adverse effects. We screened 6670 citations, reviewed 126 full-text articles, and included 89 RCTs. https://www.selleckchem.com/products/rin1.html Adjuncts included opioids, non-steroidal anti-inflammatory drugs, steroids, alpha-2 agonists, ketamine, magnesium, neosaxitoxin, and methylene blue. Alpha-2 agonists have the most evidence to support their use as adjuncts to LA infiltration. Fentanyl, ketorolac, dexamethasone, magnesium and several other agents show potential as adjuncts but require more evidence. Most studies support the safety of these agents. Our findings suggest benefits of several adjuncts to local infiltrative anesthesia for postoperative analgesia. Further well-powered RCTs are needed to compare various infiltration regimens and agents. PROTOCOL REGISTRATION PROSPERO (CRD42018103851) (https//www.crd.york.ac.uk/prospero/display_record.php?RecordID=103851).Recently, an increasing number of novel drugs were approved in oncology and hematology. Nevertheless, pharmacology progress comes with a variety of side effects, of which cytokine release syndrome (CRS) is a potential complication of some immunotherapies that can lead to multiorgan failure if not diagnosed and treated accordingly. CRS generally occurs with therapies that lead to highly activated T cells, like chimeric antigen receptor T cells or in the case of bispecific T-cell engaging antibodies. This, in turn, leads to a proinflammatory state with subsequent organ damage. To better manage CRS there is a need for specific therapies or to repurpose strategies that are already known to be useful in similar situations. Current management strategies for CRS are represented by anticytokine directed therapies and corticosteroids. Based on its pathophysiology and the resemblance of CRS to sepsis and septic shock, as well as based on the principles of initiation of continuous renal replacement therapy (CRRT) in sepsis, we propose the rationale of using CRRT therapy as an adjunct treatment in CRS where all the other approaches have failed in controlling the clinically significant manifestations.Bispecific antibodies (bsAb) and chimeric antigen receptor (CAR) T cells allow for antibody guided recruitment of T cells against tumors. Both are successfully used for treatment of CD19 expressing leukemias, but may cause cytokine release syndrome (CRS) as a major dose-limiting side effect. For CRS prevention, steroids are recommended prior to bsAb treatment, despite their well-known lymphotoxic activity. The IL-6 receptor antibody tocilizumab is established for treatment of CRS induced by CAR T cells, but was not considered for CRS prevention in bsAb therapy. We here compared the influence of dexamethasone and tocilizumab on bsAb-mediated T cell proliferation and tumor lysis in vitro and in vivo and found that dexamethasone profoundly inhibited T cell proliferation and antitumor activity as induced by two different bsAb, particularly at low effectortarget ratios, whereas tocilizumab did not affect efficacy. When we applied tocilizumab early during treatment of three patients with a newly developed PSMAxCD3 bsAb, significant CRS attenuation despite high IL-6 serum levels was observed. Thus, early IL-6 blockade may reduce the undesired sequelae of CRS upon bsAb therapy without affecting therapeutic activity, allowing in turn for safe application of effective doses.Background Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Tumor-related glucocorticoid excess is present in ~60% of patients and associated with particularly poor prognosis. Results of first clinical trials using immune checkpoint inhibitors were heterogeneous. Here we characterize tumor-infiltrating T lymphocytes (TILs) in ACC in association with glucocorticoids as potential explanation for resistance to immunotherapy. Methods We performed immunofluorescence analysis to visualize tumor-infiltrating T cells (CD3+), T helper cells (CD3+CD4+), cytotoxic T cells (CD3+CD8+) and regulatory T cells (Tregs; CD3+CD4+FoxP3+) in 146 ACC tissue specimens (107 primary tumors, 16 local recurrences, 23 metastases). Quantitative data of immune cell infiltration were correlated with clinical data (including glucocorticoid excess). Results 86.3% of ACC specimens showed tumor infiltrating T cells (7.7 cells/high power field (HPF)), including T helper (74.0%, 6.7 cells/HPF), cytotoxic T cells (84.3%, 5.7 cells/HPF) and Tregs (49.
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