6-week Mortality Research Articles

Clinical characteristics and treatment outcomes of pulmonary invasive fungal infection among adult patients with hematological malignancy in a medical centre in Taiwan, 2008–2013

This study was aimed to investigate clinical characteristics and treatment outcomes of pulmonary invasive fungal infection (IFI) among patients with hematological malignancy. All patients with hematological malignancy who were treated at a medical centre from 2008 to 2013 were evaluated. Pulmonary IFI was classified according to the European Organization for Research and Treatment of Cancer 2008 consensus. During the study period, 236 (11.3%) of 2083 patients with hematological malignancy were diagnosed as pulmonary IFI, including 41 (17.4%) proven, 75 (31.8%) probable, and 120 (50.8%) possible cases. Among the 116 patients of proven and probable cases of pulmonary IFI, aspergillosis alone (n=90, 77.6%) was predominant, followed by cryptococcosis alone (n=9, 7.8%), and mucormycosis (n=4, 3.4%). The overall incidence of patients with pulmonary IFI was 5.9 per 100 patient-years. The highest incidence (per 100 patient-year) was found in patients with acute myeloid leukaemia (13.7) followed by acute lymphoblastic leukaemia (11.3), and myelodysplastic syndrome/severe aplastic anaemia (6.7). Fourteen (5.9%) of the 236 patients with pulmonary IFI died within 12 weeks after diagnosis of pulmonary IFI. Univariate analysis revealed that elderly age (>65 years) (P=0.034), lack of response to anti-fungal treatment (P<0.001), and admission to the intensive care unit (ICU) (P<0.001) were predictors of poor prognosis. However, only admission to the ICU was an independent predictor of poor prognosis for 12-week mortality (P=0.022) based on multivariate analysis. Patients with acute leukaemia and myelodysplastic syndrome/severe aplastic anaemia were at high risk of pulmonary IFI.

Short-Term Outcome of Patients with Cirrhosis and Concurrent Portal Cavernoma Presenting with Acute Variceal Bleeding.

Background and Aim The outcome of cirrhotic patients with main portal vein occlusion and portal cavernoma after the first episode of acute variceal bleeding (AVB) is unknown. We compared short-term outcomes after AVB in cirrhotic patients with and without portal cavernoma. Methods Between January 2009 and September 2014, 28 patients with cirrhosis and portal cavernoma presenting with the first occurrence of AVB and 56 age-, sex-, and Child-Pugh score-matched cirrhotic patients without portal cavernoma were included. The primary endpoints were 5-day treatment failure and 6-week mortality. Results The 5-day treatment failure rate was higher in the cavernoma group than in the control group (32.1% versus 12.5%; p = 0.031). The 6-week mortality rate did not differ between the cavernoma and control group (25% versus 12.5%, p = 0.137). Multivariable Cox proportional hazard regression analyses revealed that 5-day treatment failure (HR = 1.223, 95% CI = 1.082 to 1.384; p = 0.001) independently predicted 6-week mortality. Conclusions Cirrhotic patients with AVB and portal cavernoma have worse short-term prognosis than patients without portal cavernoma. The 5-day treatment failure was an independent risk factor for 6-week mortality in patients with cirrhosis and portal cavernoma.

Spontaneous and Traumatic Splenic Rupture: Retrospective Clinical, B-Mode and CEUS Analysis in 62 Patients.

Introduction Both B-mode ultrasound and contrast-enhanced ultrasound (CEUS) are well established procedures when diagnosing traumatic splenic ruptures (TSR). To date, there are no data about CEUS patterns in spontaneous splenic ruptures (SSR). It remains unknown whether TSR and SSR differ with respect to clinical characteristics, B-mode and CEUS characteristics. Patients and Methods Between 12/2003 and 2/2010, n=33 SSRs and n=29 TSRs were diagnosed in a tertiary referral center. All patients were examined with B-mode and CEUS, and clinical data and the outcome were retrospectively analyzed. Results Patients with SSR were significantly older than patients with TSR (62 years vs. 44 years; p=0.01). The 4-week mortality was significantly higher in SSR than in TSR (36% vs. 0%; p=0.001). No differences between the grading of TSR and SSR could be shown in B-mode or in CEUS. Notably, CEUS was significantly superior to B-mode with respect to the grading of splenic ruptures (p=0.01). Therefore, therapeutic management was influenced by CEUS. Conclusion There are differences between SSR and TSR, especially concerning clinical data (age, course of disease and mortality). Regarding the sonographic pattern, SSR and TSR show identical grading. When splenic rupture is suspected, CEUS should always be performed to identify patients at risk who require interventional procedures.

Recalibrated MELD and hepatic encephalopathy are prognostic factors in cirrhotic patients with acute variceal bleeding.

Early TIPS placement must be considered in patients with Child-Pugh B and active bleeding at endoscopy or in patients with Child-Pugh C 10-13 and variceal bleeding. However, active bleeding at endoscopy is a subjective criterion. Moreover, a previous study has shown that a MELD-based score accurately predicted 6-week mortality and helped to stratify patients. Using a prospective series of patients included in a multicentre study before the era of early TIPS, we aimed (i) to identify factors associated with 6-week mortality, focusing on the prognostic value of active bleeding; and (ii) to assess whether a recalibrated MELD-based score accurately predicted 6-week mortality. Ancillary study of the prospective multicentre Baveno IV study, including patients with acute variceal bleeding. Two hundred and nineteen patients were analysed (Child-Pugh A/B/C=18/45/37%). The overall actuarial likelihood of survival on day 42 was 84%. The variability for the diagnosis of active bleeding at endoscopy was high (range, 41.4% to 84.6% among the centres). Active bleeding at endoscopy was not associated with 6-week mortality in the entire population or in Child-Pugh B patients. In a multivariate analysis, independent factors associated with mortality were liver function, infection, HE and HCC. The recalibrated MELD-based score was accurate in predicting 6-week mortality (AUROC=0.787). The recalibrated MELD-based score demonstrated better performance compared to the MELD score. The recalibrated MELD-based score accurately predicted mortality in our prospective cohort. Active bleeding at endoscopy had no prognostic value in cirrhotic patients presenting with acute variceal bleeding. Standardizing active bleeding assessment at endoscopy is warranted.

Shift toward greater pathologic post-myocardial infarction remodeling with loss of the adaptive hypertrophic signaling of alpha1 adrenergic receptors in mice.

RationaleWe have hypothesized that post-infarction cardiac remodeling can be influenced by shifts in the balance between intracellular mediators of “pathologic” and “physiologic” hypertrophy. Although alpha1 adrenergic receptors (alpha1-ARs) mediate pro-adaptive hypertrophy during pressure overload, little is known about their role or downstream mediators after myocardial infarction.MethodsWe performed loss-of-function experiments via coronary ligation in alpha1A-AR knockout (AKO) mice. Post-myocardial infarction (MI) remodeling was evaluated via echocardiography, quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of cardiac fetal gene expression, histologic analysis of myocyte size, post-MI fibrosis and apoptosis, and Western blot analysis of apoptotic regulators.ResultsAlpha1A-AR knockout paradoxically increased post-MI hypertrophy compared to wild type controls (WT), but also increased ventricular dilatation, fibrosis, apoptosis, and 4-week post-MI mortality (64% in AKO vs. 25% in WT, P = 0.02), suggesting a shift toward greater pathologic hypertrophy in the absence of pro-adaptive alpha1A effects. alpha1A-AR knockout increased phospho-p38 levels in the pre-MI myocardium compared to WT (0.55 ± 0.16 vs. 0.03 ± 0.01, P<0.05) but decreased phospho-ERK1/2 post-MI (0.49 ± 0.35 arbitrary units vs. 1.55 ± 0.43 in WT, P<0.05). Furthermore, expression of pro-apoptotic factor Bax was increased (1.19 ± 0.15 vs. 0.78 ± 0.08, P<0.05) and expression of anti-apoptotic factors Bcl2 was decreased (0.26 ± 0.01 vs. 0.55 ± 0.06, P<0.01) compared to WT.ConclusionsAlpha1A-AR provides an important counterbalance to pathologic pathways during post-MI remodeling that may be mediated through ERK1/2 signaling; these observations provide support for further development of an alpha1A-AR/ERK-based molecular intervention for this chronic, often fatal disease.

A simplified prognostic model to predict mortality in patients with acute variceal bleeding

BackgroundAcute variceal bleeding (AVB) is a major cause of death in patients with liver cirrhosis. The aim of this study was to investigate mortality predictors and develop a new simple prognostic model using easily verified factors at admission in AVB patients. MethodsBetween January 2009 and May 2015, 333 consecutive patients with AVB were included. A simplified prognostic model was developed using multiple logistic regression after identifying significant predictors of 6-week mortality. Mortality prediction accuracy was assessed with area under the receiver operating characteristic (AUROC) curve. We compared the new model to existing models of model for end-stage liver disease (MELD) and Child–Pugh scores. ResultsThe 6-week overall mortality rate was 12.9%. Multivariate analysis showed that C-reactive protein (CRP), total bilirubin, and the international normalized ratio were independent predictors of mortality. A new logistic model using these variables was developed. This model’s AUROC was 0.834, which was significantly higher than that of MELD (0.764) or Child–Pugh scores (0.699). Two external validation studies showed that the AUROC of our model was consistently higher than 0.8. ConclusionsOur new simplified model accurately and consistently predicted 6-week mortality in patients with AVB using objective variables measured at admission. Our system can be used to identify high risk AVB patients.

Age-Related Trends in Adults with Community-Onset Bacteremia.

To understand the epidemiological variation in bacteremia characteristics among differently aged populations, adults with community-onset bacteremia during a 6-year period were studied in a retrospective cohort. A total of 2,349 bacteremic patients were stratified into four age categories: young adults (18 to 44 years old; 196 patients; 8.3%), adults (45 to 64 years old; 707 patients; 30.1%), the elderly (65 to 84 years old; 1,098 patients; 46.7%), and the oldest old (≥85 years old; 348 patients; 14.8%). Age-related trends in critical illness (a Pitt bacteremia score of ≥4) at bacteremia onset, antibiotic-resistant pathogens (extended-spectrum β-lactamase [ESBL]-producing Escherichia coli, Klebsiella species, and Proteus mirabilis [EKP]; methicillin-resistant Staphylococcus aureus [MRSA]; and levofloxacin nonsusceptible EKP), inappropriate empirical antibiotic therapy (EAT), and 4-week mortality rate were observed. Using a multivariate regression model, critical illness at bacteremia onset (adjusted odds ratio [AOR], 9.03; P < 0.001) and inappropriate EAT (AOR, 2.67; P < 0.001) were the two leading predictors of 4-week mortality. Moreover, ESBL-producing EKP (AOR, 12.94; P < 0.001), MRSA (AOR, 8.66; P < 0.001), and levofloxacin-nonsusceptible EKP (AOR, 4.27; P < 0.001) were linked to inappropriate EAT. In conclusion, among adults with community onset bacteremia, significant positive age-related trends were noted in antibiotic-resistant pathogens and bacteremia severity, which were related to the increasing incidence of inappropriate EAT and 4-week mortality with age. Thus, different empirical antimicrobial regimens should be considered for distinct age groups.

Nonprimary PCI at hospitals without cardiac surgery on-site: Consistent outcomes for all?

The CPORT-E trial showed the noninferiority of nonprimary percutaneous coronary intervention (PCI) at hospitals without cardiac surgery on-site (SoS) compared with hospitals with SoS for 6-week mortality and 9-month major adverse cardiac events (MACE). However, target vessel revascularization (TVR) was increased at non-SoS hospitals. Therefore, we aimed to determine the consistency of the CPORT-E trial findings across the spectrum of enrolled patients. Post hoc subgroup analyses of 6-week mortality and 9-month MACE, defined as the composite of death, Q-wave myocardial infarction, or TVR, were performed. Patients with and without 9-month TVR and rates of related outcomes were compared. There was no interaction between SoS status and clinically relevant subgroups for 6-week mortality or 9-month MACE (P for any interaction=.421 and .062, respectively). In addition to increased 9-month rates of TVR and diagnostic catheterization at hospitals without SoS, non-TVR was also increased (2.7% vs 1.9%, P=.002); there was no difference in myocardial infarction-driven TVR, non-TVR, or diagnostic catheterization. Predictors of 9-month TVR included intra-aortic balloon pump use, any index PCI complication, and 3-vessel PCI, whereas predictors of freedom from TVR included SoS, discharge on a P2Y12 inhibitor, and stent implantation. The noninferiority of nonprimary PCI at non-SoS hospitals was consistent across clinically relevant subgroups. Elective PCI at an SoS hospital conferred a TVR benefit which may be related to a lower rate of referral for diagnostic catheterization for reasons other than myocardial infarction.

Endoscopic Therapy for Variceal Bleeding: from Patient Preparation to Available Techniques and Rescue Therapies

Gastrointestinal variceal bleeding (VB) is a frequent and severe complication in cirrhosis. Despite improvement in the last decades in the management of VB, the 6-week mortality after bleeding still ranges from 10 to 20%. Here, we review an up-to-date in the global management of VB. The endoscopic hemostatic treatment relies on band ligation for esophageal variceal bleeding and tissue adhesive injection for gastric variceal bleeding. In case of refractory bleeding, self-expanding metal stents or balloon tamponade can both be used as bridge to specific treatment. The use of covered TIPS provided a new step in the management of VB in severe patients, so-called “early-TIPS” in the setting of secondary prophylaxis or in all patients with refractory bleeding. The global management of patients with VB should include volume resuscitation, blood transfusion, and prevention of complications such as renal failure+/-sepsis+/-liver encephalopathy, as they drive the prognosis. Therefore, the rapid control of gastrointestinal bleeding and subsequent organ complications should be performed in specific intensive care units.

Acute kidney injury predicts mortality in cirrhotic patients with gastric variceal bleeding.

The International Club of Ascites (ICA) recently proposed a new definition of acute kidney injury (AKI) in cirrhotic patients. The study evaluated the ICA-AKI criteria and their association with the prognosis of cirrhotic patients with gastric variceal bleeding (GVB). A retrospective cohort study using prospective database of cirrhotic patients hospitalized with the first presentation of acute GVB at Taipei Veterans General Hospital from April 2007 to December 2010 was performed to evaluate the development of AKI. The study used Cox proportional hazards model to examine the association of ICA-AKI criteria and mortality. Of 113 patients, 46 (41%) fulfilled the ICA-AKI criteria and most (70%) initially had stage 1 AKI. Child-Pugh score, systemic blood pressure at admission, and number of blood units transfused before endoscopy were independent predictors of AKI. Among patients with AKI, 30% progressed to higher stages with more advanced liver disease, lower serum sodium, more units of blood transfusion, higher frequency of infection, and higher serum creatinine levels at diagnosis of AKI. The 6-week mortality rate was significantly higher in patients with AKI than in patients without AKI (37% vs 3%, P<0.001), and AKI stages were independent predictors of 3-month survival (93% in patients without AKI, 73% in stage 1, and 30% in stages 2 and 3, P=0.005). The occurrence of AKI as defined by the ICA criteria is common in cirrhotic patients with acute GVB. The presence of AKI was associated with much higher 6-week mortality, and the stages of AKI further predicted 3-month survival.

Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN

AbstractHypomethylating agents (HMAs) improve survival in patients with higher-risk myelodysplastic syndromes (MDS) but are less well-studied in lower-risk disease. We compared the safety and efficacy of low-dose decitabine vs low-dose azacitidine in this group of patients. Adults with low- or intermediate 1-risk MDS or MDS/myeloproliferative neoplasm (MPN), including chronic myelomonocytic leukemia, according to the International Prognostic Scoring System, were randomly assigned using a Bayesian adaptive design to receive either azacitidine 75 mg/m2 intravenously/subcutaneously daily or decitabine 20 mg/m2 intravenously daily for 3 consecutive days on a 28-day cycle. The primary outcome was overall response rate (ORR). Between November 2012 and February 2016, 113 patients were treated: 40 (35%) with azacitidine and 73 (65%) with decitabine. The median age was 70 years; 81% of patients were intermediate 1-risk patients. The median number of cycles received was 9. The ORRs were 70% and 49% (P = .03) for patients treated with decitabine and azacitidine, respectively. Thirty-two percent of patients treated with decitabine became transfusion independent compared with 16% of patients treated with azacitidine (P = .2). Cytogenetic response rates were 61% and 25% (P = .02), respectively. With a median follow-up of 20 months, the overall median event-free survival was 18 months: 20 and 13 months for patients treated with decitabine and azacitidine, respectively (P = .1). Treatment was well tolerated, with a 6-week mortality rate of 0%. The use of low-dose HMAs is safe and effective in patients with lower-risk MDS and MDS/MPN. Their effect on the natural history of lower-risk disease needs to be further studied. This trial was registered at clinicaltrials.gov (identifier NCT01720225).

Application of chronic liver failure-sequential organ failure assessment score for the predication of mortality after esophageal variceal hemorrhage post endoscopic ligation.

BackgroundEsophageal variceal hemorrhage (EVH) is one of the high mortality complications in cirrhotic patients. Endoscopic variceal ligation (EVL) is currently the standard therapy for EVH. However, some patients have expired during hospitalization or survived shortly after management.AimTo evaluate hospital and 6-week mortality by receiver operating characteristic (ROC) curve of chronic liver failure-sequential organ failure assessment (CLIF-SOFA) score compared to a model for end-stage liver disease (MELD) score and Child–Turcotte–Pugh (CTP) class.MethodsWe retrospectively collected 714 cirrhotic patients with EVH post EVL between July 2010 and June 2016 at Taitung MacKay Memorial Hospital, Taiwan. CLIF-SOFA score, MELD score, and CTP class were calculated for all patients admitted.ResultsAmong the 714 patients, the overall hospital and 6-week mortality rates were 6.9% (49/715) and 13.1% (94/715) respectively. For predicting hospital death, area under receiver operating characteristic curve (AUROC) values of CLIF-SOFA score, MELD score, and CTP class were 0.964, 0.876, and 0.846. For predicting 6-week death, AUROC values of CLIF-SOFA score, MELD score, and CTP class were 0.943, 0.817, and 0.834. CLIF-SOFA score had higher AUROC value with statistical significance under pairwise comparison than did MELD score and CTP class in prediction of not only hospital but also 6-week mortality. The history of hepatocellular carcinoma was the risk factor for 6-week mortality. For patients with hepatocellular carcinoma the cut-point of CLIF-SOFA score was 5.5 for 6-week mortality and 6.5 for hospital mortality on admission. For patients without hepatocellular carcinoma, the cut-point of CLIF-SOFA score was 6.5 for both 6-week and hospital mortality.ConclusionCLIF-SOFA score predicted post-EVL prognosis well. For patients without hepatocellular carcinoma, CLIF-SOFA score ≥6 suggests higher 6-week mortality and CLIF-SOFA score ≥7 suggests higher hospital mortality. For patients with hepatocellular carcinoma, CLIF-SOFA score ≥7 suggests higher 6-week and hospital mortality.

Vosaroxin in combination with decitabine in newly diagnosed older patients with acute myeloid leukemia or high-risk myelodysplastic syndrome.

Vosaroxin is an anti-cancer quinolone-derived DNA topoisomerase II inhibitor. We investigated vosaroxin with decitabine in patients ≥60 years of age with newly diagnosed acute myeloid leukemia (n=58) or myelodysplastic syndrome (≥10% blasts) (n=7) in a phase II non-randomized trial. The initial 22 patients received vosaroxin 90 mg/m2 on days 1 and 4 with decitabine 20 mg/m2 on days 1–5 every 4–6 weeks for up to seven cycles. Due to a high incidence of mucositis the subsequent 43 patients were given vosaroxin 70 mg/m2 on days 1 and 4. These 65 patients, with a median age of 69 years (range, 60–78), some of whom with secondary leukemia (22%), adverse karyotype (35%), or TP53 mutation (20%), are evaluable. The overall response rate was 74% including complete remission in 31 (48%), complete remission with incomplete platelet recovery in 11 (17%), and complete remission with incomplete count recovery in six (9%). The median number of cycles to response was one (range, 1–4). Grade 3/4 mucositis was noted in 17% of all patients. The 70 mg/m2 induction dose of vosaroxin was associated with similar rates of overall response (74% versus 73%) and complete remission (51% versus 41%, P=0.44), reduced incidence of mucositis (30% versus 59%, P=0.02), reduced 8-week mortality (9% versus 23%; P=0.14), and improved median overall survival (14.6 months versus 5.5 months, P=0.007). Minimal residual disease-negative status by multiparametric flow-cytometry at response (± 3 months) was achieved in 21 of 39 (54%) evaluable responders and was associated with better median overall survival (34.0 months versus 8.3 months, P=0.023). In conclusion, the combination of vosaroxin with decitabine is effective and well tolerated at a dose of 70 mg/m2 and warrants randomized prospective evaluation. ClinicalTrials.gov: NCT01893320

Treated secondary acute myeloid leukemia: a distinct high-risk subset of AML with adverse prognosis.

Secondary acute myeloid leukemia (s-AML) includes therapy-related AML and AML evolving from antecedent hematological disorder (AHD). s-AML arising after treating AHD likely represents a prognostically distinct, high-risk disease category. In this study, treated s-AML (ts-AML) was defined by: (1) prior diagnosis of myelodysplasia, myeloproliferative neoplasm, or aplastic anemia and (2) at least 1 therapy for that diagnosis. ts-AML was categorized by age (< or ≥60 years), and each cohort assessed for response rates and overall survival (OS) on various treatment regimens. Survival outcomes were compared against other high-risk prognostic subsets. Results showed that complete response and 8-week mortality rates were 32% and 27% in the younger, and 24% and 19% in the older age groups, respectively. There was a significant OS difference within s-AML based on prior treatment of AHD (ie, ts-AML vs s-AML with untreated AHD, 4.2 vs 9.2 months; P < .001). Survival in ts-AML was poor across both cohorts (younger and older, 5 and 4.7 months, respectively). In younger AML, survival was significantly inferior in ts-AML when compared with deletion 5/7, TP53, 3q abnormality, and therapy-related AML groups (median, 5 vs 7.9, 7.8, 7.9, and 11.2 months, respectively; P < .01). Additional adverse karyotype within ts-AML was associated with even worse outcomes (OS range, 1.6-2.8 months). ts-AML represents a very high-risk category, even in younger AML patients. s-AML should be further classified to describe ts-AML, an entity less responsive to currently applied treatment approaches. Future AML trial designs should accommodate ts-AML as a distinct subgroup.

Clinical benefits of antimicrobial de-escalation in adults with community-onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis bacteremia

The clinical benefits of an antimicrobial de-escalation strategy were compared with those of a no-switch strategy in bacteremic patients. Adults with community-onset monomicrobial Escherichia coli, Klebsiella species and Proteus mirabilis bacteremia treated empirically using broad-spectrum beta-lactams, including third-generation cephalosporins (GCs), fourth-GC or carbapenems, were treated definitively with first- or second-GCs (de-escalation group), the same regimens as empirical antibiotics (no-switch group), or antibiotics with a broader-spectrum than empirical antibiotics (escalation group). The eligible 454 adults were categorized as the de-escalation (231 patients, 50.9%), no-switch (177, 39.0%), and escalation (46, 10.1%) groups. Patients with de-escalation therapy were more often female, had less critical illness and fatal comorbidity, and had a higher survival rate than patients in the other two groups. After propensity score matching in the de-escalation and no-switch groups, critical illness at onset (Pitt bacteremia score ≥ 4; 16.5% vs. 12.7%; P = 0.34) or day 3 (2.5% vs. 2.5%; P = 1.00), fatal comorbidity (16.5% vs. 21.5%; P = 0.25), time to defervescence (4.6 vs. 4.7 days; P = 0.89), hospital stays (11.5 vs. 10.3 days; P = 0.13) and 4-week crude mortality rate (4.4% vs. 4.4%; P = 1.00) were similar. However, lower antibiotic cost (mean: 212.1 vs. 395.6 US$, P < 0.001) and fewer complications of bloodstream infections due to resistant pathogens (0% vs. 5.1%, P = 0.004) were observed in the de-escalation group. De-escalation to narrower-spectrum cephalosporins is safe and cost-effective for adults with community-onset EKP bacteremia stabilized by empirical broad-spectrum beta-lactams.

Quality of Care and Outcomes of Heart Failure Among Patients With Schizophrenia in Denmark

Research on the association between schizophrenia and the quality of care and clinical outcomes of heart failure (HF) remains sparse. This nationwide study compared the quality of care and clinical outcomes of HF among Danish patients with and without schizophrenia. In a population-based cohort study, we identified 36,718 patients with incident HF with hospital contacts, including 108 with schizophrenia, using Danish registries between 2004 and 2013. High quality of HF care was defined as receiving ≥ 80% guideline-recommended process-performance measures of care. Potential predictors of HF care among patients with schizophrenia included patient-specific factors (age, gender, Global Assessment of Functioning [GAF] score, alcohol or drug abuse, duration of schizophrenia); provider-specific factors (quality of schizophrenia care); and system-specific factors (patient-volume defined as hospital departments and clinics yearly average patient-volume of patients with incident HF). Clinical outcomes included 4-week all-cause readmission and 1-year all-cause mortality after a first-time hospital contact with incident HF. Results showed that compared with patients with incident HF who have no schizophrenia, patients with incident HF who have schizophrenia had a lower chance of receiving high-quality HF care (relative risk 0.66, 95% confidence interval 0.48 to 0.91). A high GAF score was associated with a higher chance of receiving high-quality HF care among patients with incident HF who have schizophrenia. Patients with incident HF who have schizophrenia had a higher risk of 1-year mortality (adjusted hazard ratio 2.83, 95% confidence interval 1.59 to 5.04), but not a higher risk of readmission than patients with incident HF who have no schizophrenia. In conclusion, efforts are warranted to reduce the high mortality among patients with incident HF who have schizophrenia.

Phase IB/II study of lirilumab with azacytidine (AZA) in relapsed AML.

e18505 Background: Lack of KIR-HLA class I interactions has been associated with NK-mediated antitumor efficacy in AML patients (pts) in remission upon KIR-mismatched haploidentical stem cell transplantation (SCT) (Ruggeri L et al., Science 2002). Blockade of KIR2DL1, 2 and 3 receptors induced augmented NK-cell mediated lysis of tumor cells (Romagne F et al., Blood 2009). Hypomethylating agents possess anti-leukemia activity, increase MHC II expression, and interferon-gamma signature. Methods: Pts with AML who failed prior therapy, have adequate performance status (ECOG ≤ 2) and organ function are eligible. AZA 75mg/m2 Days 1-7 was given with lirilumab on Day 8 at the dosage of 1 and 3 mg/kg in 2 consecutive cohorts of 6 pts each. Courses were repeated every 4-5 weeks. Lirilumab 3mg/kg established as recommended phase 2-dose with AZA. 13 additional pts treated at the RP2D. Responses evaluated at the end of 3 courses. Results: To date, 25 pts (16 de novo, 9 secondary AML), median age 64 years (range, 30 – 89), 52% adverse cytogenetics, median prior therapies 3 (range, 1-8), and prior alloSCT in 6 (28%) have been enrolled. All 25 pts had baseline next generation sequencing, common mutations included ASXL1 (n = 9), TP53 (n = 7), RAS (n = 4), TET2 (n = 4), and RUNX1 (n = 3). Two (8%) achieved CR/CRi (1 CR, 1 CRi) and 3 (12%) achieved hematologic improvement for an overall response rate of 20%. The median cycles to response was 3 (range, 1-11). The 8-week mortality is 12%, respectively. The median duration of response and overall survival were 2.0 months and 4.0 months, respectively (med f/u = 5.1 months). Grade 3/4 toxicities were similar to those seen with AZA based therapies in salvage including bloodstream infections in 15 (60%), 6 pneumonia, 1 UTI, 1 skin infection, 2 abdominal pain, and 1 mucositis. Immune mediated toxicities were observed in 4 (16%) pts (1 pneumonitis Grade 3, 2 colitis Grade 3, 1 colitis Grade 2). The immune mediated toxicities responded rapidly to steroids and 3 pts could be rechallenged safely with lirilumab. Six pts were postSCT and no Grade 3/4 GVHD flares were noted. Conclusions: Full doses of AZA and lirilumab were well tolerated in heavily pretreated pts with relapsed AML. The efficacy data are still preliminary and the study is ongoing. Clinical trial information: NCT02399917.

Updated results from phase II study of guadecitabine for patients with higher risk myelodysplastic syndromes or chronic myelomonocytic leukemia.

7020 Background: Improving the current response and survival outcomes of patients with higher risk MDS and CMML is fundamental. Guadecitabine is a next generation hypomethylating agent with increased length of exposure compared to decitabine and clinical activity in patients with MDS. Methods: Single arm phase 2 clinical trial of guadecitabine at a dose of 60mg/m2 sc daily for 5 days (days 1-5) every 28 days for patients with newly diagnosed MDS or CMML classified as Intermediate-2 or High risk by IPSS. Primary endpoint is complete response (CR). Responses were evaluated following the revised 2006 International Working Group criteria. Sequencing data was obtained at the time of pre-treatment evaluation by the use of a 28-gene next generation sequencing platform. Study included stopping rules for response and toxicity. Overall survival (OS) was censored at the time of transplant. Results: A total of 53 patients have been enrolled: 50 (94%) are evaluable for toxicity and 44 (83%) for response. Median age is 67 years (49-87). A total of 43 (86%) patients have MDS and 7 (14%) have CMML. A total of 21 (42%) have complex karyotype. Sequencing data was available in 48 (96%) patients with TP53 mutations being the most frequently detected in 36% patients. After a median of 6 treatment cycles (1-20), the ORR is 71% including 32% CR. Median best response occurred by 3 cycles (1-6). Seven (21%) out of 33 evaluable patients achieved a complete cytogenetic response. Ten (20%) subjects proceed to allogeneic stem cell transplantation. Median follow up was 6.3 months (0-23). Median OS is 14.1 months (CI 13.3-14.9 months) and median EFS is 8.4 months (CI 5.6-11.2 months). Forty-five (90%) patients experienced at least one AE during therapy. Most common grade 1-2 AEs included fatigue (66%), nausea (38%) and dyspnea (26%). Dose reductions due to cytopenias were required in 17 (34%) patients. Early 8-week mortality occurred in 3 (6%) patients. Conclusions: Guadecitabine is well-tolerated and active in patients with higher-risk MDS and CMML even in the presence of adverse biological features such as high frequency of complex karyotype, therapy related disease and TP53 mutations. Clinical trial information: NCT02131597.

Risk factors and clinical outcomes of breakthrough yeast bloodstream infections in patients with hematological malignancies in the era of newer antifungal agents.

Although yeast bloodstream infections (BSIs) are increasingly being reported in patients with hematological malignancies undergoing antifungal therapy, clinical information regarding breakthrough infections is scarce. The aim of this study was to determine the risk factors for and clinical outcomes of breakthrough yeast BSIs in patients with hematological malignancies in the era of newer antifungal agents. Between 2011 and 2014, all consecutive patients with hematological malignancies who developed yeast BSIs were included in a case-control study wherein breakthrough infections (cases) and de novo infections (controls) were compared. Of 49 patients with yeast BSIs, 21 (43%) met the criteria for breakthrough infections. The proportions of Candida krusei and Candida tropicalis in the cases and controls were significantly different (32% [7/22] vs. 3% [1/29], P = .015; 5% [1/22] vs. 38% [11/29], P = .007, respectively). Acute leukemia, presence of a central venous catheter and neutropenia in the 3 days prior to BSI were significant risk factors for breakthrough infections. Six-week mortality rates was 33% [7/21] in the cases and 43% [12/28] in the controls (P = .564). Refractory neutropenia and the Pitt bacteremia score were independent predictors of 6-week mortality. In conclusion, breakthrough infections accounted for a significant proportion of yeast BSIs in patients with hematological malignancies. However, these infections did not increase the risk of death by themselves. Our results suggest that current clinical management of breakthrough yeast BSIs, which includes switching to a different antifungal class and prompt catheter removal is reasonable.

Plasma Apolipoprotein A-V Predicts Long-term Survival in Chronic Hepatitis B Patients with Acute-on-Chronic Liver Failure

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening condition, and the lipid metabolism disorder is common in the development of this disease. This prospective observational study aimed to define the characteristics of plasma apolipoprotein A-V (apoA-V) in long-term outcome prediction of HBV-ACLF, and a total of 330 HBV-ACLF patients were included and followed for more than 12 months. In this cohort, the 4-week, 12-week, 24-week and 48-week cumulative mortality of HBV-ACLF was 18.2%(60/330), 50.9%(168/330), 59.7%(197/330) and 63.3%(209/330), respectively. As compared to survivors, the non-survivors had significantly lower concentrations of plasma apoA-V on admission. Plasma apoA-V concentrations were positively correlated with prothrombin time activity (PTA), and negatively correlated with interleukin-10, tumor necrosis factor-α, and iMELD scores. Though plasma apoA-V, PTA, total bilirubin(TBil) and blood urea nitrogen(BUN) were all independent factors to predict one-year outcomes of HBV-ACLF, plasma apoA-V had the highest prediction accuracy. And its optimal cutoff value for one-year survival prediction was 480.00 ng/mL, which had a positive predictive value of 84.68% and a negative predictive value of 92.23%. In summary, plasma apoA-V decreases significantly in non-survivors of HBV-ACLF, and it may be regarded as a new predictive marker for the prognosis of patients with HBV-ACLF.