Liver transplantation (LT) recipients are known to require less anesthetic agents. Providing minimally required anesthetics while avoiding awareness is especially important in LT recipients because it would help manag...Liver transplantation (LT) recipients are known to require less anesthetic agents. Providing minimally required anesthetics while avoiding awareness is especially important in LT recipients because it would help manage perioperative hemodynamic instability with less vasopressor and fast track recovery. This study aims to compare state entropy (SE) against bispectral index (BIS) during isoflurane anesthesia in LT. We adjusted anesthesia to BIS values 40 - 60, and compared it with concomitant SE values. BIS, SE values, and anesthetic requirements according to liver failure severity, etiology and LT stages were analyzed. For BIS-SE differences, SE value that is different from the concomitant BIS by more than 15 was defined as a significant disagreement. Mann Whitney, Kruskal Wallis test and a Poisson exact test were used for analysis. The BIS-SE pair sets of 2895 from 38 patients were analyzed. BIS, SE values and anesthetic requirements were significantly lower in MELD ≥ 20 (p < 0.001 in all) and in alcoholic etiology (p < 0.001 in all). For BIS-SE differences, 320 disagreement data pairs were seen at a rate of 1.33 times/hr (95% CI = [1.19, 1.48], p < 0.001). A significant disagreement was delineated in MELD score ≥ 20 (3.04 times/hr, CI = [2.64, 3.49], p < 0.001), alcoholic etiology (3.19 times/hr, [2.67, 3.78], p < 0.001) and postreperfusion stage (1.63 times/hr, [1.43, 1.85], p < 0.001). In these significant BIS-SE differences, 95.9% (307/320 disagreement data pairs) showed higher BIS than SE. In conclusion, in high MELD and alcoholic etiology, anesthetic requirements were significantly less, and BIS and SE showed great discrepancy with lower SE values. Therefore, when SE monitoring is used during LT, anesthesiologists may need to consider that in high MELD and alcoholic etiology, SE tends to show lower values than the concomitant BIS values that are within optimal anesthetic depth ranges.展开更多
Background:The combined use of anti-programmed cell death protein1(PD-1)/anti-cytotoxic T-lymphocyte associated protein 4(CTLA-4)check-point inhibitors has been effective in various cancer types.The SouthwestOncology ...Background:The combined use of anti-programmed cell death protein1(PD-1)/anti-cytotoxic T-lymphocyte associated protein 4(CTLA-4)check-point inhibitors has been effective in various cancer types.The SouthwestOncology Group(SWOG)Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors(DART)S1609 study investigated ipilimumab and nivolumab in ultra-rare cancers,including small cell carcinoma of the ovary,hypercalcemic type(SCCOHT).The purpose of the study wasto evaluate the potential clinical benefitof ipilimumab and nivolumab in patients with SCCOHT.Methods:DART was a prospective,open-labeled,multicenter(>1,000 US sites),multi-cohort phase II clinical trial of intravenous administration of ipilimumab(1 mg/kg,every 6 weeks)plus nivolumab(240 mg,every 2 weeks).The pri-mary endpoint was overall response rate[ORR,confirmed complete response(CR)and partial response(PR)]per RECIST.Secondary endpoints includedprogression-free survival(PFS),overall survival(OS),clinical benefit rate(CBR;overall response plus stable disease≥6 months),and toxicity.Immune responseswere also evaluated.Results:Six patients(median age,30.5 years;median,2 prior therapies;nopriorimmunotherapy exposure)with advanced/metastatic SCCOHT were evalu-able.ORR and CBR were both 16.7%(1/6)with one patient having a confirmedCR lasting 46.2+months.However,another patient had a confirmed immuneCR(iCR)with immune PFS(iPFS)of 53+months[ORR/iORR,33.3%(2/6)].Notably,the latter patient had a progressing lesion at 24 weeks after initialresponse,but with renewed regression with ongoing therapy,suggesting delayedpseudo-progression.At 12-months,3 patients remained alive.Median PFS was1.4 months(range,0.9 months-not reached);median OS was 14.2 months(2months-not reached).No adverse events caused treatment discontinuation.Conclusion:Two of 6 patients(33.3%)with SCCOHT achieved durable CR/iCRand long-term survival with ipilimumab plus nivolumab.Correlative studies todetermine response and resistance markers are ongoing.展开更多
Assignment of patients diagnosed with acute myeloid leukemia(AML)to the 2022 European LeukemiaNet(ELN)favorable genetic risk group has important clinical implications,as allogeneic stem cell transplantation in first c...Assignment of patients diagnosed with acute myeloid leukemia(AML)to the 2022 European LeukemiaNet(ELN)favorable genetic risk group has important clinical implications,as allogeneic stem cell transplantation in first complete remission(CR)is not advised due to a relatively good outcome of patients receiving chemotherapy alone and transplant-associated mortality.However,not all favorable genetic risk patients experience long-term relapse-free survival(RFS),making recognition of patients who would most likely be cured of high importance.展开更多
文摘Liver transplantation (LT) recipients are known to require less anesthetic agents. Providing minimally required anesthetics while avoiding awareness is especially important in LT recipients because it would help manage perioperative hemodynamic instability with less vasopressor and fast track recovery. This study aims to compare state entropy (SE) against bispectral index (BIS) during isoflurane anesthesia in LT. We adjusted anesthesia to BIS values 40 - 60, and compared it with concomitant SE values. BIS, SE values, and anesthetic requirements according to liver failure severity, etiology and LT stages were analyzed. For BIS-SE differences, SE value that is different from the concomitant BIS by more than 15 was defined as a significant disagreement. Mann Whitney, Kruskal Wallis test and a Poisson exact test were used for analysis. The BIS-SE pair sets of 2895 from 38 patients were analyzed. BIS, SE values and anesthetic requirements were significantly lower in MELD ≥ 20 (p < 0.001 in all) and in alcoholic etiology (p < 0.001 in all). For BIS-SE differences, 320 disagreement data pairs were seen at a rate of 1.33 times/hr (95% CI = [1.19, 1.48], p < 0.001). A significant disagreement was delineated in MELD score ≥ 20 (3.04 times/hr, CI = [2.64, 3.49], p < 0.001), alcoholic etiology (3.19 times/hr, [2.67, 3.78], p < 0.001) and postreperfusion stage (1.63 times/hr, [1.43, 1.85], p < 0.001). In these significant BIS-SE differences, 95.9% (307/320 disagreement data pairs) showed higher BIS than SE. In conclusion, in high MELD and alcoholic etiology, anesthetic requirements were significantly less, and BIS and SE showed great discrepancy with lower SE values. Therefore, when SE monitoring is used during LT, anesthesiologists may need to consider that in high MELD and alcoholic etiology, SE tends to show lower values than the concomitant BIS values that are within optimal anesthetic depth ranges.
基金National Institutes of HealthNational Cancer Institute,Grant/Award Numbers:U10CA180888,U10CA180819,UG1CA233320,UG1CA233193,UG1CA233198,UG1CA233340Bristol Myers Squibb Company。
文摘Background:The combined use of anti-programmed cell death protein1(PD-1)/anti-cytotoxic T-lymphocyte associated protein 4(CTLA-4)check-point inhibitors has been effective in various cancer types.The SouthwestOncology Group(SWOG)Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors(DART)S1609 study investigated ipilimumab and nivolumab in ultra-rare cancers,including small cell carcinoma of the ovary,hypercalcemic type(SCCOHT).The purpose of the study wasto evaluate the potential clinical benefitof ipilimumab and nivolumab in patients with SCCOHT.Methods:DART was a prospective,open-labeled,multicenter(>1,000 US sites),multi-cohort phase II clinical trial of intravenous administration of ipilimumab(1 mg/kg,every 6 weeks)plus nivolumab(240 mg,every 2 weeks).The pri-mary endpoint was overall response rate[ORR,confirmed complete response(CR)and partial response(PR)]per RECIST.Secondary endpoints includedprogression-free survival(PFS),overall survival(OS),clinical benefit rate(CBR;overall response plus stable disease≥6 months),and toxicity.Immune responseswere also evaluated.Results:Six patients(median age,30.5 years;median,2 prior therapies;nopriorimmunotherapy exposure)with advanced/metastatic SCCOHT were evalu-able.ORR and CBR were both 16.7%(1/6)with one patient having a confirmedCR lasting 46.2+months.However,another patient had a confirmed immuneCR(iCR)with immune PFS(iPFS)of 53+months[ORR/iORR,33.3%(2/6)].Notably,the latter patient had a progressing lesion at 24 weeks after initialresponse,but with renewed regression with ongoing therapy,suggesting delayedpseudo-progression.At 12-months,3 patients remained alive.Median PFS was1.4 months(range,0.9 months-not reached);median OS was 14.2 months(2months-not reached).No adverse events caused treatment discontinuation.Conclusion:Two of 6 patients(33.3%)with SCCOHT achieved durable CR/iCRand long-term survival with ipilimumab plus nivolumab.Correlative studies todetermine response and resistance markers are ongoing.
基金supported by the National Library of Medicine of the National Institutes of Health under award R01LM013879Research reported in this publication was also supported in part by the National Cancer Institute at the National Institutes of Health under award R01CA262496,R01CA284595,R01CA283574,U10CA180821,U10CA180882,U24CA196171,UG1CA233327,UG1CA233331,UG1CA233338,UG1CA 233339,R35CA197734,and P30CA016058+4 种基金the Coleman Leukemia Research Foundationan ASH Junior Faculty Scholar Award and ASH Bridge Grant(to A.-K.E.)the Leukemia Research Foundation(to A.-K.E.)the Leukemia&Lymphoma Society(to A.-K.E.)The D.Warren Brown Foundation。
文摘Assignment of patients diagnosed with acute myeloid leukemia(AML)to the 2022 European LeukemiaNet(ELN)favorable genetic risk group has important clinical implications,as allogeneic stem cell transplantation in first complete remission(CR)is not advised due to a relatively good outcome of patients receiving chemotherapy alone and transplant-associated mortality.However,not all favorable genetic risk patients experience long-term relapse-free survival(RFS),making recognition of patients who would most likely be cured of high importance.
