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Of the 486,000 burn injuries that required medical treatment in the USA in 2016, 40,000 people were hospitalized, with > 3,000 fatalities. Integrin agonist After burn injury, humans are at increased risk of sepsis and mortality from infections caused by Pseudomonas aeruginosa (PA), an opportunistic pathogen. We hypothesize that systemic events were initiated from the burn that increased the host’s susceptibility to PA. A non-lethal 10% total body surface area (TBSA), full-thickness flame burn was performed in CD-1 mice without and with subsequent PA (strain M2) infection. The LD50 for subcutaneous infection with PA M2 at the burn site immediately after the burn decreased by 6-logs with mortality occurring between 18 and 26 hours, compared with PA-infected mice without burn injury. Bacteria in distal organs were detected by 18 hours, concurrent with the onset of clinical symptoms. Serum pro-inflammatory cytokines (IL-6, IL-1β, IFN-γ, and TNF-α) and the anti-inflammatory cytokine, IL-10, were first detected at 12 hours post-burn with infection and continued to increase until death. Directly after burn alone, serum levels of HMGB1, a danger-associated molecular pattern and TLR4 agonist, transiently increased to 50 ng/mL before returning to 20 ng/mL. Burn with PA infection increased serum HMGB1 concentrations >10-fold (250 ng/mL) at the time of death. This HMGB1-rich serum stimulated TLR4-mediated NF-κB activation in a TLR4-reporter cell line. Treatment of infected burned mice with P5779, a peptide inhibitor of HMGB1, increased the mean survival from 23 to 42 hours (P less then 0.0001). We conclude that the high level of serum HMGB1, which preceded the increase in pro-inflammatory cytokines, is associated with post-burn mortality.

Induction therapy is a critical component of the therapy of high-risk neuroblastoma. We aimed to assess if the Memorial Sloan Kettering Cancer Center (MSKCC) N5 induction regimen (MSKCC-N5) would improve metastatic complete response (mCR) rate and 3-year event-free survival (EFS) compared with rapid COJEC (rCOJEC; cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C]).

Patients (age 1-20 years) with stage 4 neuroblastoma or stage 4/4s aged < 1 year with

amplification were eligible for random assignment to rCOJEC or MSKCC-N5. Random assignment was stratified according to national group and metastatic sites. Following induction, therapy comprised primary tumor resection, high-dose busulfan and melphalan, radiotherapy to the primary tumor site, and isotretinoin with ch14.18/CHO (dinutuximab beta) antibody with or without interleukin-2 immunotherapy. The primary end points were mCR rate and 3-year EFS.

A total of six hundred thirty patients were randomly assigned to men for International Society of Pediatric Oncology European Neuroblastoma Group.

No difference in outcome was observed between rCOJEC and MSKCC-N5; however, acute toxicity was less with rCOJEC, and therefore rCOJEC is the preferred induction regimen for International Society of Pediatric Oncology European Neuroblastoma Group.Selective autophagy is the lysosomal degradation of specific intracellular components sequestered into autophagosomes, late endosomes, or lysosomes through the activity of selective autophagy receptors (SARs). SARs interact with autophagy-related (ATG)8 family proteins via sequence motifs called LC3-interacting region (LIR) motifs in vertebrates and Atg8-interacting motifs (AIMs) in yeast and plants. SARs can be divided into two broad groups soluble or membrane bound. Cargo or substrate selection may be independent or dependent of ubiquitin labeling of the cargo. In this review, we discuss mechanisms of mammalian selective autophagy with a focus on the unifying principles employed in substrate recognition, interaction with the forming autophagosome via LIR-ATG8 interactions, and the recruitment of core autophagy components for efficient autophagosome formation on the substrate. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.Recent observations indicate that, rather than being an all-or-none response, phagocytosis is finely tuned by a host of developmental and environmental factors. The expression of key phagocytic determinants is regulated via transcriptional and epigenetic means that confer memory on the process. Membrane traffic, the cytoskeleton, and inside-out signaling control the activation of phagocytic receptors and their ability to access their targets. An exquisite extra layer of complexity is introduced by the coexistence of distinct “eat-me” and “don’t-eat-me” signals on targets and of corresponding “eat” and “don’t-eat” receptors on the phagocyte surface. Moreover, assorted physical barriers constitute “don’t-come-close-to-me” hurdles that obstruct the engagement of ligands by receptors. The expression, mobility, and accessibility of all these determinants can be modulated, conferring extreme plasticity on phagocytosis and providing attractive targets for therapeutic intervention in cancer, atherosclerosis, and dementia. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.

The COVID-19 pandemic is an unprecedented global crisis profoundly affecting oncology care delivery.

This study will describe the occupational and personal consequences of the COVID-19 pandemic on oncologist well-being and patient care.

Four virtual focus groups were conducted with US ASCO member oncologists (September-November 2020). Inquiry and subsequent discussions centered on self-reported accounts of professional and personal COVID-19 experiences affecting well-being, and oncologist recommendations for well-being interventions that the cancer organization and professional societies (ASCO) might implement were explored. Qualitative interviews were analyzed using Framework Analysis.

Twenty-five oncologists were interviewed median age 44 years (range 35-69 years), 52% female, 52% racial or ethnic minority, 76% medical oncologists, 64% married, and an average of 51.5 patients seen per week (range 20-120). Five thematic consequences emerged (1) impact of pre-COVID-19 burnout, (2) occupational or professional limitations and adaptations, (3) personal implications, (4) concern for the future of cancer care and the workforce, and (5) recommendations for physician well-being interventions.