Citations

Abstract The recent pace, extent, and impact of paradigm-changing cancer prevention science has been remarkable. The American Association for Cancer Research (AACR) convened a 3-day summit, aligned with five research priorities: (i) Precancer Atlas (PCA). (ii) Cancer interception. (iii) Obesity-cancer linkage, a global epidemic of chronic low-grade inflammation. (iv) Implementation science. (v) Cancer disparities. Aligned with these priorities, AACR co-led the Lancet Commission to formally endorse and accelerate the NCI Cancer Moonshot program, facilitating new global collaborative efforts in cancer control. The expanding scope of creative impact is perhaps most startling—from NCI-funded built environments to AACR Team Science Awarded studies of Asian cancer genomes informing global primary prevention policies; cell-free epigenetic marks identifying incipient neoplastic site; practice-changing genomic subclasses in myeloproliferative neoplasia (including germline variant tightly linked to JAK2 V617F haplotype); universal germline genetic testing for pancreatic cancer; and repurposing drugs targeting immune- and stem-cell signals (e.g., IL-1β, PD-1, RANK-L) to cancer interception. Microbiota-driven IL-17 can induce stemness and transformation in pancreatic precursors (identifying another repurposing opportunity). Notable progress also includes hosting an obesity special conference (connecting epidemiologic and molecular perspectives to inform cancer research and prevention strategies), co-leading concerted national implementation efforts in HPV vaccination, and charting the future elimination of cancer disparities by integrating new science tools, discoveries and perspectives into community-engaged research, including targeted counter attacks on e-cigarette ad exploitation of children, Hispanics and Blacks. Following this summit, two unprecedented funding initiatives were catalyzed to drive cancer prevention research: the NCI Cancer Moonshot (e.g., PCA and disparities); and the AACR-Stand Up To Cancer bold “Cancer Interception” initiative.

For the hundreds of thousands of premenopausal women who are diagnosed annually with endocrine-sensitive breast cancer, treatment strategies are complex. For many, chemotherapy may not be necessary, and endocrine therapy decision making is paramount. Options for adjuvant endocrine regimens include tamoxifen for 5 years, tamoxifen for 10 years, ovarian function suppression (OFS) plus tamoxifen for 5 years, and OFS plus an aromatase inhibitor for 5 years. There are modest differences in efficacy between these regimens, with a benefit from OFS most obvious among patients with higher-risk disease; therefore, choosing which should be used for a given patient requires consideration of expected toxicities and patient preferences. An aromatase inhibitor cannot be safely prescribed without OFS in this setting. Additional research is needed to determine whether genomic tests such as Prosigna and Endopredict can help with decision making about optimal duration of endocrine therapy for premenopausal patients. Endocrine therapy side effects can include hot flashes, sexual dysfunction, osteoporosis, and infertility, all of which may impair quality of life and can encourage nonadherence with treatment. Ovarian function suppression worsens menopausal side effects. Hot flashes tend to be worse with tamoxifen/OFS, whereas sexual dysfunction and osteoporosis tend to be worse with aromatase inhibitors/OFS. Pregnancy is safe after endocrine therapy, and some survivors can conceive naturally. Still, embryo or oocyte cryopreservation should be considered at the time of diagnosis for patients with endocrine-sensitive disease who desire future childbearing, particularly if they will undergo chemotherapy.

Summary All commonly used general anesthetics have been shown to cause neurotoxicity in animal models, including nonhuman primates. Opinion, however, remains divided over how cumulative evidence from preclinical and human studies in this field should be interpreted and its translation to current practices in pediatric anesthesia and surgery. A group of international experts in laboratory and clinical sciences recently convened in Genoa, Italy, to evaluate the current state of both laboratory and clinical research and discuss future directions for basic, translational, and clinical studies in this field. This paper describes those discussions and conclusions. A central goal identified was the importance of continuing to pursue laboratory research efforts to better understand the biological pathways underlying anesthesia neurotoxicity. The distinction between basic and translational experimental designs in this field was highlighted, and it was acknowledged that it will be important for future animal research to try to causally link structural changes with long‐term cognitive abnormalities. While inherent limitations will continue to affect the ability of even large observational cohorts to determine if anesthesia impacts neurodevelopment or behavioral outcomes, the importance of conducting further large well‐designed cohort studies was also emphasized. Adequately powered cohorts could clarify which populations are at increased risk, provide information on environmental and healthcare‐related risk modifiers, and guide future interventional trials. If anesthetics cause structural or functional adverse neurological effects in young children, alternative or mitigating strategies need to be considered. While protective or mitigating strategies have been repeatedly studied in animals, there are currently no human data to support alternative anesthetic strategies in clinical practice. Lastly, it was noted that there is still considerable debate over the clinical relevance of anesthesia neurotoxicity, and the need to evaluate the impact of other aspects of perioperative care on neurodevelopment must also be considered.

AbstractBackgroundEnteral nutrition (EN) is a safe and cost‐effective intervention with significant morbidity and mortality benefit that can also be associated with complications. Peristomal infections can occur in 5%–30% of cases after percutaneous endoscopic gastrostomy placement. Despite this common occurrence, widespread use of objective diagnostic criteria is not prevalent, possibly leading to overuse of antibiotics.MethodsAll patients who were reporting symptoms consistent with peristomal infection were evaluated. Criteria based on erythema, induration, and exudates were applied with cumulative score ≥8 indicating peristomal infection. All patients were followed, with additional factors being collected if available.ResultsForty‐three patients noted complaints consistent with peristomal infection. In patients with a score <8 (n = 16), only 2 required antibiotics (12.5%) and 1 patient was hospitalized (6.3%). In patients with a score ≥8 (n = 27), 16 had a score of 8 or 9; all patients responded to antibiotics (100%), and 1 was hospitalized (6.3%). In patients with a score ≥10, all (100%) were treated with antibiotics. Five of 11 (45%) patients were hospitalized, with the most common diagnosis being sepsis. Of the baseline variables analyzed, higher body mass index correlated with score ≥10 (26.36 ± 2.94 vs 22.91 ± 4.35 in score <9, P = .0128).ConclusionsObjective criteria were effective in risk stratifying patients who presented with reports of peristomal infection. Patients with a score <8 tended to be at low risk, scores of 8–9 were of moderate risk, and patients with a score ≥10 were at high risk and required very close monitoring or hospitalization.

AbstractBackground: Since initial report in 1972, misconnections continue to be an issue, especially in hospitalized patients with multiple access devices. A new small‐bore connector standard (ENFit) has been proposed in order to minimize misconnections. Methods: Commercially available finalized ENFit tubes of a variety of sizes (14 French [Fr] size, 18Fr, 20Fr, 24Fr, and low‐profile) were obtained for current testing. Variety of commercially available formulas including blenderized tube feeding (BTF) products (Jevity 1 Cal, Abbott Nutrition, Abbott Park, IL; Nourish, Functional Formularies, Centerville, OH; Real Food Blends, Chesterton, IN) were tested. Results: Data from individual measurements were aggregated for ENFit and legacy tubes and revealed higher syringe compression force in legacy tubes compared with ENFit tubes for 20Fr size with Jevity formula. Our institution's BTF formula revealed that legacy tubes had lower syringe compression force than ENFit tubes for 14Fr tube size. Remaining measurements revealed no significant difference. Model 1 of regression analysis revealed that only formula and tube size were significant with R2 of 0.63. Model 2 evaluating the impact of tube size, blender, time of blending, and legacy vs ENFit revealed that tube size, blender used, and blending time were significant with legacy vs ENFit being nonsignificant (R2 of 0.72). Conclusions: Overall, only a small number of tube sizes (14Fr and 20Fr) with selected formulas revealed a significant difference between ENFit and Legacy tubes, with remaining studies finding no significant difference. Regression analysis revealed that variables such as formula, size of tube, blender used, and time of blending may have more impact on compression force.

Undifferentiated uterine sarcomas (UUS) are a heterogenous group of high-grade mesenchymal tumors. Although these tumors are highly aggressive, a subset of patients may experience long-term survival. These tumors have previously been divided morphologically into uniform and pleomorphic types. A previous study demonstrated that a mitotic index cutoff of 25 mitoses/10 high-power fields (corresponding to 11.16 mitotic figures/mm2) could successfully divide tumors into 2 prognostic groups with significantly different overall survival. The goals of the current study were to (1) validate this mitotic index cutoff in an independent, multicenter cohort and (2) explore the prognostic value of the mitotic index groups in relation to other clinicopathologic variables. Cases were included from 3 independent institutions: The Norwegian Radium Hospital, The Mayo Clinic, and Skåne University Hospital. A total of 40 tumors were included after central review. All cases were negative for the YWHAE-FAM22A/B and JAZF1-JJAZ1 translocations. Survival data were available on all patients. In this study, one-third of patients with UUS survived beyond 5 years. The crude (unadjusted) Cox Proportional Hazards model revealed a number of parameters that significantly impacted overall survival, including mitotic index group, patient age, stage, and the presence of tumor necrosis. Classification into the uniform and pleomorphic types was not prognostic. Combining these parameters into an adjusted model revealed that only the mitotic index group and stage were prognostic. On the basis of these findings, it is proposed that UUS be subdivided into “mitogenic” and “not otherwise specified” types.