Six-week Mortality Research Articles

Liver Severity Score-Based Modeling to Predict Six-Week Mortality Risk Among Hospitalized Cirrhosis Patients With Upper Gastrointestinal Bleeding

Liver Severity Score-Based Modeling to Predict Six-Week Mortality Risk Among Hospitalized Cirrhosis Patients With Upper Gastrointestinal Bleeding

Trends in Hospitalizations of Esophageal Varices From 2011 to 2018: A United States Nationwide Study.

Prevalence of gastroesophageal varices is around 50% of patients with cirrhosis. In compensated cirrhosis they are present in 30-40%. Progression from small to large varices occurs at rate of 10-12% annually. That percentage increases significantly in decompensated liver cirrhosis with gastroesophageal varices found in 85% of patients. Variceal hemorrhage occurs at a rate around 10-15% per year. The outcome of variceal hemorrhage depends on the severity of liver disease, size of varices, and presence of stigmata of recent bleeding (red whale sign). Six-week mortality of variceal hemorrhage ranges between 15% and 25%. Without treatment, variceal hemorrhage tends to recur in 60% of patients within 1 - 2 years. The aim of the study was to assess demographics of esophageal varices with and without bleeding, geographic distribution, comorbidities, outcomes, main payers, and cost of hospitalizations. The National Inpatient Sample (NIS) database from year 2011 to 2018 was used. Patients who had a primary diagnosis of esophageal varices with or without bleeding were identified using the International Classification of Diseases, Ninth Revision (ICD-9) codes (456.0 for esophageal varices with bleeding, and 456.1 for esophageal varices without bleeding), and International Classification of Diseases, 10th Revision (ICD-10) codes (I85.01 for esophageal varices with bleeding, and I85.00 for esophageal varices without bleeding) in the first two discharge diagnoses. The propensity score to calculate the inverse probability treatment weighting (IPTW) to adjust between the differences of the compared groups was implemented. Two groups were compared in terms of their hospitalization outcomes, including LOS, hospital charges, hospital mortality, and disposition. A total of 322,761 patients were admitted with esophageal varices between 2011 and 2018, with 236,802 (73.6%) had bleeding esophageal varices and 85,959 (26.4%) had nonbleeding esophageal varices. The majority of the patients from both groups were white (66%), covered with Medicare (38% in the esophageal varices with bleeding vs. 41% in the nonbleeding group). There was a steady increase of patients admitted with nonbleeding esophageal varices. Most common comorbidities were liver diseases, alcohol abuse, uncomplicated hypertension and depression in both groups. There were no significant changes in OLS over the years in both groups, but there was a significant increase in hospital charges, especially in the patients with bleeding esophageal varices starting in 2015, and no change in mortality throughout the years. Regarding hospital disposition, there was a notable decline in rehab discharge in the bleeding esophageal varices group. Esophageal varices with and without bleeding have been steadily increasing since the beginning of this century. This may result in a substantial impact on increasing health care costs and utilization due to acute variceal hemorrhage. Odds of death, transfer to urban hospital, and transfer to visiting nursing assistance remained unchanged.

61. Development and external validation of predictive algorithms for six-week mortality in spinal metastasis using 4304 patients from five institutions

<h3>BACKGROUND CONTEXT</h3> Historically, spine surgeons used expected postoperative survival of three months to help select candidates for operative intervention in spinal metastasis. However, this cutoff has been challenged by the development of minimally invasive techniques, novel biologics and advanced radiotherapy. Recent studies have suggested that life expectancy of six weeks may be enough to achieve significant improvements in postoperative health-related quality of life. <h3>PURPOSE</h3> The purpose of this study was to develop a model capable of predicting six-week mortality in patients with spinal metastases treated with radiation or surgery. <h3>STUDY DESIGN/SETTING</h3> Retrospective review was conducted at five large tertiary centers in the United States and Taiwan. <h3>PATIENT SAMPLE</h3> The development cohort consisted of 3,001 patients undergoing radiotherapy and/or surgery for spinal metastases from one institution. The validation institutional cohort consisted of 1,303 patients from four independent, external institutions. <h3>OUTCOME MEASURES</h3> The primary outcome was six-week mortality. <h3>METHODS</h3> Five models were considered to predict six-week mortality, and the model with the best performance across discrimination, calibration, decision-curve analysis and overall performance was integrated into an open access web-based application. <h3>RESULTS</h3> The most important variables for prediction of six-week mortality were albumin, primary tumor histology, absolute lymphocyte, three or more spine metastasis, and ECOG score. The elastic-net penalized logistic model was chosen as the best performing model with AUC 0.84 on evaluation in the independent testing set. On external validation in the 1,303 patients from the four independent institutions, the model retained good discriminative ability with an area under the curve of 0.81. <h3>CONCLUSIONS</h3> As spinal metastasis patients with shorter life expectancy are considered for operative intervention, the algorithm developed and externally validated in this study may be helpful for preoperative planning, multidisciplinary management, and shared decision-making. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Development and external validation of predictive algorithms for six-week mortality in spinal metastasis using 4,304 patients from five institutions

BACKGROUND CONTEXTHistorically, spine surgeons used expected postoperative survival of 3-months to help select candidates for operative intervention in spinal metastasis. However, this cutoff has been challenged by the development of minimally invasive techniques, novel biologics, and advanced radiotherapy. Recent studies have suggested that a life expectancy of 6 weeks may be enough to achieve significant improvements in postoperative health-related quality of life. PURPOSEThe purpose of this study was to develop a model capable of predicting 6-week mortality in patients with spinal metastases treated with radiation or surgery. STUDY DESIGN/SETTINGA retrospective review was conducted at five large tertiary centers in the United States and Taiwan. PATIENT SAMPLEThe development cohort consisted of 3,001 patients undergoing radiotherapy and/or surgery for spinal metastases from one institution. The validation institutional cohort consisted of 1,303 patients from four independent, external institutions. OUTCOME MEASURESThe primary outcome was 6-week mortality. METHODSFive models were considered to predict 6-week mortality, and the model with the best performance across discrimination, calibration, decision-curve analysis, and overall performance was integrated into an open access web-based application. RESULTSThe most important variables for prediction of 6-week mortality were albumin, primary tumor histology, absolute lymphocyte, three or more spine metastasis, and ECOG score. The elastic-net penalized logistic model was chosen as the best performing model with AUC 0.84 on evaluation in the independent testing set. On external validation in the 1,303 patients from the four independent institutions, the model retained good discriminative ability with an area under the curve of 0.81. The model is available here: https://sorg-apps.shinyapps.io/spinemetssurvival/. CONCLUSIONSWhile this study does not advocate for the use of a 6-week life expectancy as criteria for considering operative management, the algorithm developed and externally validated in this study may be helpful for preoperative planning, multidisciplinary management, and shared decision-making in spinal metastasis patients with shorter life expectancy.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study

ObjectiveThe objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. DesignProspective descriptive multicenter cohort study. Setting26 Intensive care units (ICU) from Andalusian region in Spain. Patients or participantsConsecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. InterventionsNone. VariablesVariables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. Results495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. ConclusionAge, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks.Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab.Lopinavir/ritonavir administration is identified as a protective factor.

Cerebral aspergillosis in the era of new antifungals: The CEREALS national cohort study Nationwide CEREbral Aspergillosis Lesional study (CEREALS)

Cerebral aspergillosis (CA) is a life-threatening disease for which diagnosis and management remain challenging. Detailed analyses from large cohorts are lacking. We included 119 cases of proven (n=54) or probable (n=65) CA diagnosed between 2006 and 2018 at 20 French hospitals. Data were collected at baseline and during follow-up. Cerebral imaging was reviewed centrally by two neuroradiologists. The most frequent underlying conditions were hematological malignancy (40%) and solid organ transplantation (29%). Galactomannan was detected in the serum of 64% of patients. In 75% of cases, at least one of galactomannan, Aspergillus PCR, and β-d-glucan was positive in the cerebrospinal fluid. Six-week mortality was 45%. Two distinct patterns of disease were identified according to presumed route of dissemination. Presumed haematogenous dissemination (n=88) was associated with a higher frequency of impaired consciousness (64%), shorter time to diagnosis, the presence of multiple abscesses (70%), microangiopathy (52%), detection of serum galactomannan (69%) and Aspergillus PCR (68%), and higher six-week mortality (54%). By contrast, contiguous dissemination from the paranasal sinuses (n=31) was associated with a higher frequency of cranial nerve palsy (65%), evidence of meningitis on cerebral imaging (83%), macrovascular lesions (61%), delayed diagnosis, and lower six-week mortality (30%). In multivariate analysis and in a risk prediction model, haematogenous dissemination, hematological malignancy and the detection of serum galactomannan were associated with higher six-week mortality. Distinguishing between hematogenous and contiguous dissemination patterns appears to be critical in the workup for CA, as they are associated with significant differences in clinical presentation and outcome.

Factors associated with mechanical ventilation in SARS-CoV-2 patients treated with high-flow nasal cannula oxygen and outcomes.

Five percent of patients infected with SARS‐CoV‐2 require advanced respiratory support. The high‐flow nasal cannula oxygenotherapy (HFNCO) appears to be effective and safe to reduce the need for mechanical ventilation. However, the factors associated with HFNCO failure as well as the outcomes of patients receiving this noninvasive respiratory strategy remain unclear. Thus, we performed this study to determine factors leading to intubation of SARS‐CoV‐2 patients treated with HFNCO and patients’ outcomes. We retrospectively analyzed the medical charts of patients admitted in our ICU center for acute respiratory failure due to SARS‐CoV‐2 infection and who initially benefited from HFNCO, between September 1, 2020, and March 1, 2021. We included all adults patients who received HFNCO and compared two groups: those treated with HFNCO alone and those who failed HFNCO. Patients treated with HFNCO and secondarily limited to the use of mechanical ventilation were excluded from the analysis. Sixty‐nine patients were included, 33 were treated with HFNCO alone and 36 failed HFNCO. We found more patients with shock in the HFNCO failure group (p = 0.001). The mean IGSII score was higher in the HFNCO failure group (p < 0.001). The minimum PaO2/FiO2 was lower in the HFNCO failure group (p = 0.024). The length of stay in ICU was higher in the HFNCO failure group (p < 0.001). The mean duration of HFNCO before intubation was 1.77 days. Six‐week mortality was higher in the HFNCO failure group (p = 0.034). Ten patients had a complication during intubation. The HFNCO leads to reduce the intubation rate, the length of stay in ICU, and the mortality. Determining the factors associated with HFNCO failure is important to avoid complications following late intubation.

THE ROLE OF SERUM WISTERIA FLORIBUNDA AGGLUTINATION POSITIVE MAC-2 BINDING PROTEIN IN PREDICTION OF ESOPHAGEAL VARICES IN HEPATITIS C VIRUS-RELATED CIRRHOTIC PATIENTS

HCV infection is one of the main causes of chronic liver disease worldwide.Liver cirrhosis is the final stage of chronic liver injury with a high mortality. The transition from compensated forms to decompensated cirrhosis occurs at a rate of 5-7% per year. Once patients have developed the first episode of decompensation, complications tend to accumulate and life expectancy is dramatically decreased. Portal Hypertension is the initial and main consequence of cirrhosis and is responsible for the majority of its complications such as ascites, hepatic encephalopathy and gastroesophageal varices. Variceal haemorrhage is considered the most lethal complications of portal hypertension with a six-week mortality after an episode of bleeding ranges between 15% and 25%. So early detection and management of esophageal varices is very crucial in cirrhotic patients.Serum WFA- M2BP, is a cell adhesive glycoprotein of the extracellular matrix secreted as a ligand of galectin 3.It is secreted from many cell types, particularly hepatocytes. It has been shown to increase with the progression of liver fibrosis.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.

ObjectiveThe objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators.DesignProspective descriptive multicenter cohort study.Setting26 Intensive care units (ICU) from Andalusian region in Spain.Patients or participantsConsecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30.InterventionsNone.VariablesVariables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied.Results495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470 U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72 h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor.ConclusionAge, APACHE II, SOFA > value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks.Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab.Lopinavir/ritonavir administration is identified as a protective factor.

Disseminated Mucormycosis in Immunocompromised Children: Are New Antifungal Agents Making a Difference? A Multicenter Retrospective Study.

Background: Mucormycosis is a life-threatening infection with a tendency for angioinvasion that may lead to progressive dissemination. Disseminated mucormycosis, defined as the involvement of two or more non-contiguous sites, is rare in children, and data concerning its management and outcome are scarce. The aim of this study was to assess the contemporary management strategies and outcomes of disseminated mucormycosis in the pediatric population. Methods: We conducted a retrospective search in six large tertiary medical centers for all cases of disseminated mucormycosis that occurred between 2009–2020 in patients aged 1–20 years. Results: Twelve cases were identified. Underlying conditions included hematological malignancies (n = 10), solid tumor (post-autologous hematopoietic stem cell transplantations; n = 1), and solid organ (liver) transplantation (n = 1). In all cases, amphotericin B formulations were administered as first-line therapy; in eight cases, they were also administered in combination with an echinocandin or triazole. Seven patients underwent surgical debridement procedures. The six-week mortality was 58%. Among the patients diagnosed between 2009–2015, one of the six survived, and of those diagnosed between 2016–2020, four of the six were salvaged. Conclusions: Disseminated mucormycosis is a life-threatening and often fatal disease, and improved diagnostic and therapeutic strategies are needed. Nevertheless, in this population-based study, five patients (42%) were salvaged through combined liposomal amphotericin/triazole treatment and extensive surgical interventions.

Development of a risk scoring system for prognostication in HIV-related toxoplasma encephalitis

BackgroundThis study aims to evaluate specific risk factors influencing prognosis of HIV-infected patients with toxoplasma encephalitis (TE) in order to develop a prognostic risk scoring system for them.MethodsThis is a six-center retrospective study of hospitalized HIV/TE patients. Data including six-week mortality after diagnosis, baseline characteristics, clinical features, laboratory tests and radiological characteristics of eligible patients were assimilated for risk model establishing.ResultsIn this study, the six-week mortality among 94 retrospective cases was 11.7% (11/94). Seven specific risk factors, viz. time from symptom onset to presentation, fever, dizziness, CD4+ T-cell counts, memory deficits, patchy brain lesions, and disorders of consciousness were calculated to be statistically associated with mortality. A criterion value of ‘9’ was selected as the optimal cut-off value of the established model. The AUC of the ROC curve of this scoring model was 0.976 (p < 0.001). The sensitivity and specificity of the risk scoring model was 100.0 and 86.9%, respectively, which were 81.8 and 94.1% of this scoring model in the verification cohort, respectively.ConclusionsThe developed scoring system was established with simple risk factors, which also allows expeditious implementation of accurate prognostication, and appropriate therapeutic interventions in HIV-infected patients with TE.

S0634 Gastric Variceal Bleeding Carries Worse Prognosis Than Other Causes of Upper Gastrointestinal Bleeding in Cirrhosis

INTRODUCTION: Gastric varices (GV) are present in approximately 20% of patients with cirrhosis and have been previously associated with poor outcomes. In part, this is because they are often not amenable to standard endoscopic band ligation. However endoscopic and endovascular interventions have been studied for GV management. Our single center study describes the characteristics and outcomes associated with GV bleeding (GVB) as well as the utilization of various therapies. METHODS: Adults admitted at an academic medical center between 2012 and 2018 with cirrhosis and upper gastrointestinal bleed (GIB) were included; those with lower GIB, malignancy as primary cause of liver disease, or previous liver transplant were excluded. The primary outcome was 6-week mortality from GVB. Secondary outcomes included endoscopic findings, endoscopic hemostasis rates, and 5-day survival. Logistic and linear regression analyzed outcomes. RESULTS: Of 208 included patients, 31 (14.9%) had GV and 75 (36.1%) had esophageal varices (EV) without GV. The identified source of bleeding was GV in 17 patients, 8 GV were actively bleeding on index endoscopy. Baseline characteristics between EV and GV bleeds were similar (Table 1). The primary type of GV identified was GOV1, and a variety of endoscopic therapies were utilized (Table 2). When controlling for age, gender, admission hemoglobin, INR, and Child Class, patients with active GVB had much lower rates of endoscopic hemostasis than those with EV bleed (25 vs 83.7%, OR 0.03, 95% CI 0.002-0.36, P < 0.01). While 13 (76.5%) GV bleed patients were eligible for transjugular intrahepatic portosystemic shunt (TIPS), only 3 received TIPS during hospitalization, 3 received TIPS post-discharge and 4 were transplanted. Six-week mortality for GV was 31.3% and 5-day mortality was 25%. In addition, overall clinical outcomes were much worse for those with GVB than other GIB causes (Table 3). When GV was identified as the source of bleed, mortality was numerically higher at 6 weeks (50 vs 12.5%, P = 0.10) as well as 5 days (37.5 vs 12.5%, P = 0.24) among patients who did not receive either endoscopic or endovascular therapies. CONCLUSION: Our single center case series correlates with previous findings that GVB is highly morbid, despite use of therapeutic options. GV patients had less hemostasis on endoscopy than EV and despite advanced therapies, mortality was higher than other upper GIB causes. Overall, advanced therapies trended towards improved outcomes but may have been underutilized.Table 1.: Patient Baseline CharacteristicsTable 2.: Types of gastric varices seen and clinical managementTable 3.: Outcomes of gastric variceal bleed

Changes in the management of variceal gastrointestinal haemorrhage in our department

Introduction: Variceal bleeding is a life-threatening complication of portal hypertension with a six-week mortality rate of approximately 20%. Aim: To analyse whether the changes introduced in the treatment of variceal gastrointestinal haemorrhage in our department affected the mortality rate of these patients. Method: A retrospective method was used to compare the data of patients treated with variceal bleeding in 2014 and 2015. In 2015, two changes were made in the treatment of patients with variceal bleeding: all patients were treated in the subintensive care unit and terlipressin was administered to all patients susceptible to variceal haemorrhage. Bleeding was mitigated by means of sclerotherapy and/or ligation. Significance was calculated using Student’s t-test, then we performed logistic regression to find out what treatment factors affect mortality rate. Patients: 2014 vs. 2015 figures – number of patients: 24 vs. 30, average age: 59.8 vs. 57.6 years, male (%): 70.8 vs. 66.7. There were no significant differences between the Child–Pugh stages of the two years, p = 0.53. For the analysis we also grouped patients based on whether irrespective of the year of treatment they were administered terlipressin or not. Number of patients: 22 vs. 32, average age: 60.4 vs. 57.4, male (%): 63.6 vs. 70.6. Results: Mortality in 2015 and 2014: 23% and 33%, respectively. Mortality of patients treated with terlipressin: 18.2 vs. 34.4, p = 0.09. Child–Pugh stages had the strongest influence on mortality (stage A vs. B p = 0.05, stage A vs. C p = 0.02). Terlipressin administered in Child–Pugh stage C reduced mortality at a rate bordering on significance (p = 0.055). Conclusion: Despite the comparatively small number of cases, the changes introduced in our department in 2015 in the treatment of variceal gastrointestinal haemorrhages resulted in a significant reduction of hospital mortality rates. Orv Hetil. 2020; 161(15): 583–587.

1696. Epidemiology, Clinical Characteristics and Outcomes of Invasive Aspergillosis in a Tertiary Care Hospital in Mexico

BackgroundInvasive aspergillosis is an important cause of life-threatening infection in immunocompromised patients. The objective was to describe the epidemiology, clinical characteristics, and outcome of patients with invasive aspergillosis (IA) in a tertiary care center in Mexico.MethodsA laboratory-based survey was done to identify patients with positive Aspergillus culture or galactomannan from 2014 to 2018. The medical records were reviewed to include patients with proven and probable IA, according to the EORTC criteria. Descriptive analysis of clinical characteristics and risk factors for 6-week mortality was made through X2, T-test or Mann–Whitney test. A multivariate logistic regression model including variables with a P-value of <0.2 in univariate analysis was made.Results240 cases of IA were identified: 193 (80%) probable, 27 (11%) proven, and 20 (8.3%) not meeting the EORTC criteria but considered infection. 53% were male, median age was 44 years (IQR 28–58), 78 (32.5%) had acute leukemia (AL), 42 (17.5%) hematological neoplasia, 29 (12%) hematopoietic stem-cell transplant (HSCT), 25 (10.4%) solid-organ transplant and 44 (18.3%) autoimmune diseases, 17.5% patients with AL underwent induction remission chemotherapy of which 31% received antifungal prophylaxis. Among patients with IA, 183 (82%) had a positive galactomannan and 109 (45%) had a culture with Aspergillus. Eleven had > 1 species: 55/120 (46%) were A. fumigatus, 18 (15%) A. niger and 18 (15%) A. flavus. Pulmonary disease occurred in 214 (89%). 212 patients (88%) received antifungal treatment with a median duration of 42 days (IQR 20–42). 129 (61%) received voriconazole (VRC), 20 (8.3%) Amphotericin B and 20(8.3%) were randomized to a posaconazole vs. VRC trial. Six-week mortality was 35% (n = 85). Lymphopenia (OR 3.6; 95% CI 1.4–9.0), liver failure (OR 3.3; 95% CI 1.7–6.5) and older age (OR 1.03; 95% CI 1.01–1.05) (marginally) were independently associated with increased 6-week mortality.Conclusion240 patients with IA were identified in a 5-year period in a tertiary care center. Most had hematological neoplasias and low prevalence of antimold prophylaxis due to economical reasons. Six-week mortality was 35%, nonsurvivors had liver failure and lymphopenia more often. Increased awareness to prevent IA is needed. Disclosures All authors: No reported disclosures.

Real-world use-Isavuconazole at a large academic medical center.

Isavuconazole use in the real-world setting has not been extensively described. Subgroups of patients with particular prognostic significance, such as previous triazole prophylaxis or treatment and the important subgroup treated empirically for invasive fungal infection, have beforehand been excluded from trials. We aimed to determine treatment response and safety in these patients at a large US transplant and cancer centre. We conducted a retrospective cohort study of all adult inpatients administered ≥3 doses of isavuconazole between June 2015 and October 2017. Ninety-one adults were identified. Six (7%) received primary prophylaxis, 10 (11%) treatment then secondary prophylaxis and 75 (82%) treatment only. Overall treatment response was 62%. Six-week mortality was 24%. Sixty-three per cent of 32 patients treated with isavuconaozle following prophylaxis with another antifungal agent exhibited a treatment response. Among 49 patients switched from treatment with another agent, 53% had a treatment response. Thirty-four patients received isavuconazole empirically, and 65% demonstrated a treatment response. Individuals given isavuconazole prophylaxis developed no breakthrough invasive fungal infections. One patient discontinued isavuconazole due to hepatotoxicity. Real-world isavuconazole use appears safe and is associated with treatment responses in varied patients including critically important subgroups previously unreported.

Impact of sepsis and non-communicable diseases on prognostic models to predict the outcome of hospitalized chronic liver disease patients.

AIMTo evaluate the impact of sepsis and non-communicable diseases (NCDs) on the outcome of decompensated chronic liver disease (CLD) patients.METHODSIn this cross-sectional study, medical records of patients with CLD admitted to the Gastroenterology unit at the Aga Khan University Hospital were reviewed. Patients older than 18 years with decompensation of CLD (i.e., jaundice, ascites, encephalopathy, and/or upper gastrointestinal bleed) as the primary reason for admission were included, while those who were admitted for reasons other than decompensation of CLD were excluded. Each patient was followed for 6 wk after index admission to assess mortality, prolonged hospital stay (> 5 d), and early readmission (within 7 d).RESULTSA total of 399 patients were enrolled. The mean age was 54.3 ± 11.7 years and 64.6% (n = 258) were male. Six-week mortality was 13% (n = 52). Prolonged hospital stay and readmission were present in 18% (n = 72) and 7% (n = 28) of patients, respectively. NCDs were found in 47.4% (n = 189) of patients. Acute kidney injury, sepsis, and non-ST elevation myocardial infarction were found in 41% (n = 165), 17.5% (n = 70), and 1.75% (n = 7) of patients, respectively. Upon multivariate analysis, acute kidney injury, non-ST elevation myocardial infarction, sepsis, and coagulopathy were found to be statistically significant predictors of mortality. While chronic kidney disease (CKD), low albumin, and high Model for End-Stage Liver Disease (MELD)-Na score were found to be statistically significant predictors of morbidity. Addition of sepsis in conventional MELD score predicted mortality even better than MELD-Na (area under receiver operating characteristic: 0.735 vs 0.686; P < 0.001). Among NCDs, CKD was found to increase morbidity independently.CONCLUSIONAddition of sepsis improved the predictability of MELD score as a prognostic marker for mortality in patients with CLD. Presence of CKD increases the morbidity of patients with CLD.

Bacterial infections in acute variceal hemorrhage despite antibiotics-a multicenter study of predictors and clinical impact.

Current guidelines recommend antibiotic prophylaxis in all patients presenting with cirrhosis and acute variceal hemorrhage (AVH). We aimed to evaluate the characteristics and clinical impact of "early" infections (developing within 14 days) of AVH in a real-world setting. We analyzed retrospective data from a cohort of 371 adult patients with cirrhosis and AVH all of whom had received antibiotic prophylaxis (74% men; mean age 56 years), admitted to tertiary care hospitals in Edmonton, Alberta, Canada, and Barcelona, Spain. Sensitivity analyses were presented for culture-positive (confirmed) infections. The mean MELD was 16. Fifty-two percent of patients received quinolones, 45% third-generation cephalosporins and 3% other antibiotics. Fourteen percent (51/371) developed an infection within 14 days of AVH. Seventy-five percent of infections were culture positive and occurred at a mean of six days from AVH. When all infections were considered, respiratory infections were the most common (53%) followed by urinary tract infections (17%) and bacteremia (16%). Resistance patterns differed between countries. Outpatient antibiotic prophylaxis (OR 5.4) and intubation (OR 2.6) were independent predictors of bacterial infection. Bacterial infection (OR 2.6) and the MELD (OR 1.2) were independent predictors of six-week mortality. Early bacterial infections develop in 14% of cirrhotic patients with AVH despite antibiotic prophylaxis, and have a negative impact on six-week mortality. Intubation and outpatient antibiotic prophylaxis are associated with increased risk of early bacterial infections. Patients at risk should be followed closely with prompt infection workup and local antibiogram-based expansion of antibiotic therapy in case of clinical decline.

Propranolol versus carvedilol for the primary prophylaxis of variceal bleeding: a proposed multicenter, randomized, double-blind trial

Background: Bleeding from esophageal varices is one of the most frequent and deadly complications of liver cirrhosis, with six-week mortality rates as high as 30%. The estimation of portal pressure by means of hepatic venous pressure gradient (HVPG) measurement remains the single most accurate predictor of bleeding in individual patients. An increasing number of studies have reported a greater reduction of HVPG using carvedilol compared to the current standard of care, propranolol; however, there are still no clinical trials comparing carvedilol to propranolol head-to-head for the prophylaxis of variceal bleeding. Aims: To compare carvedilol versus propranolol for the prevention of a first variceal bleed (primary prophylaxis) in patients with cirrhosis and esophageal varices. Methods: This is a proposed design and protocol for a multicenter, randomized, active-controlled, double-blind, parallel group, phase III superiority trial, including a total of 452 patients with cirrhosis and esophageal varices that are at high risk of bleeding. Potential impact of the study: In view of the encouraging results obtained with carvedilol in prior studies, we believe a trial comparing propranolol to carvedilol in terms of clinical outcomes is necessary to clearly establish whether carvedilol should become the treatment of choice for the primary prohylaxis of variceal bleeding. If this trial is successfully conducted, results can be expected to have a substantial impact on clinical practice and future research directions.

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.

Initial use of combination treatment does not impact survival of 106 patients with haematologic malignancies and mucormycosis: a propensity score analysis

In view of the poor outcomes associated with mucormycosis in patients with haematologic malignancies (HM) and haematopoietic cell transplant recipients, antifungal combinations are frequently used, yet the value of such strategy remains unclear. We reviewed the records of HM patients treated for mucormycosis from 1994 to 2014. The primary outcome was 6-week mortality after treatment initiation. Of the 106 patients identified, 44% received monotherapy and 56% received combination treatment as initial therapy. Six-week mortality was associated with disseminated mucormycosis (p 0.018), active malignancy (p <0.01), higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (p <0.001), neutropenia (p 0.049), lymphopenia (p 0.0003) and intensive care unit (ICU) admission at diagnosis (p 0.0001). Survivors were more likely to have localized mucormycosis (p <0.01) and to receive hyperbaric oxygen therapy (p 0.02). There were no differences in mortality between monotherapy and combination treatment groups (43% vs. 41%; p 0.85). In multivariate analysis, lymphopenia (odds ratio (OR), 5.5; 95% confidence interval (CI), 1.9–15.9; p 0.002) and ICU admission at diagnosis (OR, 8.2; 95% CI, 2.3–29.2; p 0.001) were associated with increased mortality. Localized mucormycosis was associated with better outcome (OR, 0.06; 95% CI, 0.01–0.6; p 0.019). Initial combination treatment had no impact on mortality, even after propensity score adjustment (OR, 0.8; 95% CI, 0.3–2.4; p 0.69). A weighted mortality risk score was then calculated for each patient based on the factors independently associated with mortality and baseline APACHE II score. In the low-risk group (n = 49), 13% of monotherapy versus 15% of combination therapy patients died within 6 weeks (p >0.99). In the high-risk group (n = 57), 71% of monotherapy versus 61% of combination therapy patients died within 6 weeks (p 0.42). With the current status of mucormycosis diagnosis, there was no difference in mortality in HM patients, whether they received monotherapy or combination treatment as initial therapy. Earlier diagnosis and immune reconstitution are unmet needs to affect outcomes.