Case report: Interstitial implantation radiotherapy combined with immunotherapy and GM-CSF in oligometastatic platinum-resistant ovarian cancer

BackgroundTreatment for platinum-resistant ovarian cancer is challenging. Currently, platinum-resistant ovarian cancer is typically treated with non-platinum single-agent chemotherapy ± bevacizumab, but the prognosis is often extremely poor. In the treatment of platinum-resistant ovarian cancer patients, reports of triple therapy with interstitial implantation radiotherapy combined with immunotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) (PRaG for short) are relatively rare.Case descriptionHere, we report a patient with oligometastatic platinum-resistant ovarian cancer. The patient achieved partial response (PR) of the lesion and sustained benefit for more than six months after receiving interstitial implantation radiotherapy combined with immunotherapy along with GM-CSF.ConclusionThis triple therapy may provide additional options for these patients

Inverse design of artificial skins

Mimicking the perceptual functions of human cutaneous mechanoreceptors, artificial skins or flexible pressure sensors can transduce tactile stimuli to quantitative electrical signals. Conventional methods to design such devices follow a forward structure-to-property routine based on trial-and-error experiments/simulations, which take months or longer to determine one solution valid for one specific material. Target-oriented inverse design that shows far higher output efficiency has proven effective in other fields, but is still absent for artificial skins because of the difficulties in acquiring big data. Here, we report a property-to-structure inverse design of artificial skins based on small dataset machine learning, exhibiting a comprehensive efficiency at least four orders of magnitude higher than the conventional routine. The inverse routine can predict hundreds of solutions that overcome the intrinsic signal saturation problem for linear response in hours, and the solutions are valid to a variety of materials. Our results demonstrate that the inverse design allowed by small dataset is an efficient and powerful tool to target multifarious applications of artificial skins, which can potentially advance the fields of intelligent robots, advanced healthcare, and human-machine interfaces

Intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilisation (IVF) in couples with non-severe male infertility (NSMI-ICSI) : protocol for a multicentre randomised controlled trial

Funding This study was supported by National Key Research and Development Program of China (2016YFC1000201; 2018YFC1002104) and the National Science Foundation of China (81730038). The study funders had no rule in the study design, implementation, analysis, manuscript, preparation or decision to submit this article for publication.Peer reviewedPublisher PD

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial

Background: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. Results: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference − 0.40 [95% CI − 0.71 to − 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference − 1.6% [95% CI − 4.3% to 1.2%]; P = 0.42) between groups. Conclusions: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. Trial registration: ISRCTN, ISRCTN12233792. Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial.

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial (vol 26, 46, 2022)

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

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

A Novel Approach for Evaluating the Contraction of Hypo-Peritectic Steels during Initial Solidification by Surface Roughness

The contraction of peritectic steels in the initial solidification has an important influence on the formation of surface defects of continuously cast slabs. In order to understand the contraction behavior of the initial solidification of steels in the mold, the solidification process and surface roughness in a commercial hypo-peritectic and several non-peritectic steels were investigated using Confocal Scanning Laser Microscope (CSLM). The massive transformation of delta-Fe (δ) to austenite (γ) was documented in the hypo-peritectic steel, which caused surface wrinkles and greatly increases the surface roughness of samples in the experiments. Surface roughness (Ra(δ→γ)) was calculated to evaluate the contraction level of the hypo-peritectic steel due to δ–γ transformation. The result shows that the surface roughness method can facilitate the estimation of the contraction level of peritectic transformation over a wide range of cooling rates