Integrating genetic and epigenetic factors in chronic myeloid leukemia risk assessment: toward gene expression-based biomarkers.

Cancer treatment is constantly evolving from a one-size-fits-all towards bespoke approaches for each patient. In certain solid cancers, including breast and lung, tumor genome profiling has been incorporated into therapeutic decision-making. For chronic phase chronic myeloid leukemia (CML), while tyrosine kinase inhibitor therapy is the standard treatment, current clinical scoring systems cannot accurately predict the heterogeneous treatment outcomes observed in patients. Biomarkers capable of segregating patients according to outcome at diagnosis are needed to improve management, and facilitate enrollment in clinical trials seeking to prevent blast crisis transformation and improve the depth of molecular responses. To this end, gene expression (GE) profiling studies have evaluated whether GE signatures at diagnosis are clinically informative. Patient material from a variety of sources has been profiled using microarrays, RNA sequencing and, more recently, single-cell RNA sequencing. However, differences in the cell types profiled, the technologies used, and the inherent complexities associated with the interpretation of genomic data pose challenges in distilling GE datasets into biomarkers with clinical utility. The goal of this paper is to review previous studies evaluating GE profiling in CML, and explore their potential as risk assessment tools for individualized CML treatment. We also review the contribution that acquired mutations, including those seen in clonal hematopoiesis, make to GE profiles, and how a model integrating contributions of genetic and epigenetic factors in resistance to tyrosine kinase inhibitors and blast crisis transformation can define a route to GE-based biomarkers. Finally, we outline a four-stage approach for the development of GE-based biomarkers in CML.

Efficacy and cost analysis of eltrombopag in thrombocytopenia and poor graft function post allogeneic hematopoietic cell transplantation.

Eltrombopag has shown efficacy in the treatment of thrombocytopenia and poor graft function (PGF) after allogeneic hematopoietic cell transplantation (HCT) in retrospective observational studies, but is not approved for this indication. The cost of this drug is also a major concern in publicly funded health care systems. We collected data about patients who received eltrombopag for thrombocytopenia or PGF after HCT. Post-HCT thrombocytopenia, PGF, and eltrombopag response were defined as per previously published criteria. Primary outcome was treatment efficacy and secondary outcome was cost comparison between estimated treatment cost prior to and after initiation of eltrombopag. Seventeen patients (males 70.6%; median age = 58) received eltrombopag. Isolated thrombocytopenia was present in 11.8% (n = 2) patients while PGF was present in 88.2% (n = 15) of patients. After 8 weeks of treatment at the maximum dose of 150 mg orally daily, overall response rate (ORR) was seen in 76.5% (13/17) of patients: complete response (CR) in 10/13 patients and partial response (PR) in 3/13 patients. The use of eltrombopag was associated with an overall decrease in the total weekly care costs (5021 vs 2,524 CA$; P = 0.04). Thus, Eltrombopag is an efficacious and possibly cost-effective therapy for thrombocytopenia and PGF after allogeneic HCT.

Hepatitis C treatment strategies in prisons: A cost-effectiveness analysis.

In Australian prisons approximately 20% of inmates are chronically infected with hepatitis C virus (HCV), providing an important population for targeted treatment and prevention. A dynamic mathematical model of HCV transmission was used to assess the impact of increasing direct-acting antiviral (DAA) treatment uptake on HCV incidence and prevalence in the prisons in New South Wales, Australia, and to assess the cost-effectiveness of alternate treatment strategies. We developed four separate models reflecting different average prison lengths of stay (LOS) of 2, 6, 24, and 36 months. Each model considered four DAA treatment coverage scenarios of 10% (status-quo), 25%, 50%, and 90% over 2016-2045. For each model and scenario, we estimated the lifetime burden of disease, costs and changes in quality-adjusted life years (QALYs) in prison and in the community during 2016-2075. Costs and QALYs were discounted 3.5% annually and adjusted to 2015 Australian dollars. Compared to treating 10% of infected prisoners, increasing DAA coverage to 25%, 50%, and 90% reduced HCV incidence in prisons by 9-33% (2-months LOS), 26-65% (6-months LOS), 37-70% (24-months LOS), and 35-65% (36-months LOS). DAA treatment was highly cost-effective among all LOS models at conservative willingness-to-pay thresholds. DAA therapy became increasingly cost-effective with increasing coverage. Compared to 10% treatment coverage, the incremental cost per QALY ranged from $497-$569 (2-months LOS), -$280-$323 (6-months LOS), -$432-$426 (24-months LOS), and -$245-$477 (36-months LOS). Treating more than 25% of HCV-infected prisoners with DAA therapy is highly cost-effective. This study shows that treating HCV-infected prisoners is highly cost-effective and should be a government priority for the global HCV elimination effort.

A national analysis of pediatric firearm violence and the effects of race and insurance status on risk of mortality.

OBJECTIVES: To perform a national analysis of pediatric firearm violence (PFV), hypothesizing that black and uninsured patients would have higher risk of mortality. METHODS: The Trauma Quality Improvement Program (2014-2016) was queried for PFV patients ≤16 years-old. Multivariable logistic regression models on all patients and a subset excluding severe brain injuries were performed. RESULTS: The PFV mortality rate was 11.2%. 66.5% of PFV patients were black (p < 0.001). Deceased patients were more likely to be uninsured (14.5% vs. 5.3%, p < 0.001). Black race was an associated risk factor for mortality in patients without severe brain injury (OR 5.26, CI 1.00-27.47, p = 0.049) but not for the overall population (OR 1.32, CI 0.68-2.56, p = 0.39). CONCLUSION: Nearly two-thirds of PFV patients were black. Contrary to previous studies, black and uninsured pediatric patients did not have an increased risk of mortality overall. However, in a subset of patients without severe brain injury, black race was associated with increased mortality risk. SUMMARY: Between 2014 and 2016 the mortality rate for pediatric firearm violence (PFV) in children 16 years and younger was 11.2%. Although two-thirds of PFV patients were black, black race and lack of insurance were not risk factors of mortality for the overall population. Once patients with severe brain injury were excluded, black race and became associated with an increased risk of mortality.

Pilot prospective study of Frailty and Functionality in routine clinical assessment in allogeneic hematopoietic cell transplantation.

A Frailty and Functionality evaluation for alloHCT was implemented using existing resources. We describe the implementation of this evaluation across all ages and at first consultation, and correlate results with posttransplant outcomes in 168 patients. The evaluation consists of: Clinical Frailty Scale (CFS), Instrumental Activities of Daily Living (IADL), grip strength (GS), timed up and go test (TUGT), self-rated health question (SRH), Single question of Falls, albumin and C-Reactive Protein (CRP) levels. Median time to perform the evaluation was 5-6 min. Median age was 58 years (range: 19-77) and median follow-up was 5.3 months. TUGT > 10 s (HR 2.92; p = 0.003), raised CRP (HR 4.40; p < 0.001), and hypoalbuminemia (HR 2.10; p = 0.043) were significant risk factors for worse overal survival (OS). CFS ≥ 3 (HR 3.11; p = 0.009), TUGT > 10 s (HR 3.47; p = 0.003), GS (HR 2.56; p = 0.029), SRH ( 10 s and raised CRP were significant predictors for worse OS and NRM. SRH (

Predictors of mortality and cost among surgical patients requiring rapid response team activation.

Background: Prior studies of rapid response team (RRT) implementation for surgical patients have demonstrated mixed results with respect to reductions in poor outcomes. The aim of this study was to identify predictors of in-hospital mortality and hospital costs among surgical inpatients requiring RRT activation. Methods: We analyzed data prospectively collected from May 2012 to May 2016 at The Ottawa Hospital. We included patients who were at least 18 years of age, who were admitted to hospital, who received either preoperative or postoperative care, and and who required RRT activation. We created a multivariable logistic regression model to describe mortality predictors and a multivariable generalized linear model to describe cost predictors. Results: We included 1507 patients. The in-hospital mortality rate was 15.9%. The patient-related factors most strongly associated with mortality included an Elixhauser Comorbidity Index score of 20 or higher (odds ratio [OR] 3.60, 95% confidence interval [CI] 1.96-6.60) and care designations excluding admission to the intensive care unit and cardiopulmonary resuscitation (OR 3.52, 95% CI 2.25-5.52). The strongest surgical predictors included neurosurgical admission (OR 2.09, 95% CI 1.17-3.75), emergent surgery (OR 2.04, 95% CI 1.37-3.03) and occurrence of 2 or more operations (OR 1.73, 95% CI 1.21-2.46). Among RRT factors, occurrence of 2 or more RRT assessments (OR 2.01, 95% CI 1.44-2.80) conferred the highest mortality. Increased cost was strongly associated with admitting service, multiple surgeries, multiple RRT assessments and medical comorbidity. Conclusion: RRT activation among surgical inpatients identifies a population at high risk of death. We identified several predictors of mortality and cost, which represent opportunities for future quality improvement and patient safety initiatives.

Contexte: Les études sur la mobilisation d'équipes d'intervention rapide (EIR) auprès de patients en chirurgie ont donné des résultats mitigés quant à la réduction des issues négatives. La présente étude visait à déterminer les facteurs prédictifs de coûts pour les hôpitaux et de mortalité chez les patients en chirurgie nécessitant la mobilisation d'une EIR. Méthodes: Nous avons analysé des données recueillies de manière prospective de mai 2012 à mai 2016 à l'Hôpital d'Ottawa. Nous avons inclus les patients hospitalisés de 18 ans et plus qui ont reçu des soins préopératoires ou postopératoires et qui ont nécessité l'intervention d'une EIR. Nous avons ensuite créé un modèle de régression logistique multivariée pour décrire les facteurs prédictifs de mortalité et un modèle linéaire généralisé multivarié pour décrire les facteurs prédictifs de coûts. Résultats: Nous avons retenus 1507 patients. Le taux global de mortalité à l'hôpital était de 15,9 %. Les principaux facteurs de mortalité liés au patient étaient un indice de comorbidité d'Elixhauser supérieur ou égal à 20 (rapport de cotes [RC] 3,60, intervalle de confiance [IC] à 95 % 1,96­6,60) et des objectifs de soins excluant l'admission à l'unité des soins intensifs et la réanimation cardiorespiratoire (RC 3,52, IC à 95 % 2,25­5,52). Les principaux facteurs prédictifs liés aux interventions sont l'admission en neurochirurgie (RC 2,09, IC à 95 % 1,17­3,75), l'intervention chirurgicale d'urgence (RC 2,04, IC à 95 % 1,37­3,03) et le fait d'avoir subi au moins 2 opérations (RC 1,73, IC à 95 % 1,21­2,46). Parmi les facteurs liés aux EIR, la tenue d'au moins 2 évaluations par l'EIR s'accompagnait du mortalité le plus élevé (RC 2,01, IC à 95 % 1,44­2,80). L'augmentation des coûts était étroitement associée au service d'admission, aux interventions chirurgicales multiples, aux évaluations multiples par l'EIR et à la comorbidité médicale. Conclusion: La mobilisation d'EIR auprès de patients en chirurgie permet de mettre en évidence une population à risque élevé de décès. Nous avons découvert plusieurs facteurs prédictifs de mortalité et de coûts, dont on pourra se servir pour améliorer la qualité des soins et la sécurité des patients.

Laparoscopic Inguinal Hernia Repair: Undervalued by the Relative Value Unit System.

Work relative value units (wRVUs) serve as a proxy of surgeon's effort, technical skill, and time to determine reimbursement. The aim of this study is to determine how accurately wRVUs reflect the work effort of surgeons performing laparoscopic inguinal hernia repair (LIHR) as compared to open repair (OIHR). Within the National Surgical Quality Improvement Program database, 40 099 patients who underwent LIHR and 99 176 patients who underwent OIHR between 2012 and 2017 were identified. Mean wRVUs, wRVUs per minute, and operative times were compared between 8 groups based on clinical factors (unilateral vs. bilateral; obstructed vs. non-obstructed; primary vs. recurrent; 2 × 2 × 2 = 8). In both aggregate and matched cohorts, wRVUs for LIHR were significantly lower than OIHR in all 8 categories (P < .001). On regression analysis, the mean difference in assigned vs. calculated relative value units (RVUs) was most divergent among unilateral, recurrent, obstructed IHR (3.12 mean RVUs, P < .001). Despite the rising utilization of LIHR, current wRVUs significantly undervalue this technique across all categories and consequently the work of surgeons who perform laparoscopic procedures. This RVU discrepancy in an increasing minimally invasive, value-driven surgical environment calls for more objective criteria to assign RVUs, whereby the value is measured by operative complexity-patient clinical factors and severity of the hernia itself-not solely operative technique.

Implementation of a multidisciplinary perinatal emergency response team improves time to definitive obstetrical evaluation and fetal assessment.

BACKGROUND: Trauma is the leading cause of nonobstetric death during pregnancy and is associated with an increased risk of maternal and fetal mortality. In an effort to improve the delivery of care to pregnant trauma patients, we developed an institutional multidisciplinary quality initiative designed to improve response times of nontrauma specialists and ensure immediate availability of resources. We hypothesized that implementation of a perinatal emergency response team (PERT) would improve time to patient and fetal evaluation and monitoring by the obstetrics (OB) team and improve both maternal and fetal outcomes. METHODS: We performed a 6-year (2012-2018) retrospective cohort analysis of consecutive pregnant trauma patients presenting to our university-affiliated, level I trauma center. Patients in the pre-PERT cohort (before April 2015) were compared with a post-PERT cohort. Variables analyzed included patient demographics, mechanism of injury, Injury Severity Score, and level of trauma activation. The main outcome measure was time to OB evaluation. Secondary outcomes included time to cardiotocometry, and mortality. RESULTS: Of 92 pregnant trauma patients, there were 50 patients (54.3%) in the pre-PERT cohort and 42 (45.7%) in the post-PERT group. Blunt injuries predominated (98.9%), with the most common mechanism being motor vehicle collisions (76.1%), followed by assaults (13%) and falls (6.5%). The mean time to obstetrical evaluation was 44 minutes in the pre-PERT cohort compared with 14 minutes in the post-PERT cohort (p = 0.001). There was a significant decrease in level I (highest acuity) trauma activations pre-PERT and post-PERT (46% vs. 21%, p = 0.01), and the time to cardiotocography was significantly decreased post-PERT implementation (72 vs. .37 min, p = 0.01) CONCLUSION: Implementation of a multidisciplinary PERT improves time to evaluation by the OB team and time to cardiotocometry in the pregnant trauma patient. LEVEL OF EVIDENCE: Retrospective review, level IV.

Follow-up trends after emergency department discharge for acutely symptomatic hernias: A southwestern surgical congress multi-center trial.

BACKGROUND: The objective of this multi-center study was to examine the follow-up trends after emergency department (ED) discharge in a large and socioeconomically diverse patient population. METHODS: We performed a 3-year retrospective analysis of adult patients with acutely symptomatic hernias who were discharged from the EDs of five geographically diverse hospitals. RESULTS: Of 674 patients, 288 (43%) were evaluated in the clinic after discharge from the ED and 253 (37%) underwent repair. Follow-up was highest among those with insurance. A total of 119 patients (18%) returned to the ED for hernia-related complaints, of which 25 (21%) underwent urgent intervention. CONCLUSION: The plan of care for patients with acutely symptomatic hernias discharged from the ED depends on outpatient follow-up, but more than 50% of patients are lost to follow-up, and nearly 1 in 5 return to the ED. The uninsured are at particularly high risk.

Impact of central nervous system involvement in AML on outcomes after allotransplant and utility of pretransplant cerebrospinal fluid assessment.

OBJECTIVE: The primary objective was to assess the effect of central nervous system involvement in acute myeloid leukemia (CNS-AML) on outcomes after allogeneic hematopoietic stem cell transplant (allo-HCT). The secondary objective was to assess the utility of pretransplant cerebrospinal fluid (CSF) assessment in AML. METHODS: We retrospectively analyzed survival outcomes in 338 adult AML patients (with and without CNS-AML) after allo-HCT. CNS involvement was defined as clinical, pathological, or radiological evidence of CNS involvement any time after diagnosis. RESULTS: The median follow-up in surviving patients was 23.7 months. Twenty-five patients (7.4%) had prior history of CNS disease, with normal CSF pretransplant. Three patients had CSF blasts detected for the first time at pretransplant evaluation (0.88%). The 2-year OS and RFS in groups with and without CNS involvement were not significantly different. Patients with CNS-AML had significantly higher 1-year cumulative incidence of relapse (29.7% vs 16.9%, P = .048). Age more than 65 years and absence of marrow remission at transplant were significant adverse factors for survival. CONCLUSION: CNS-AML is not an independent risk factor for survival after allo-HCT, but can be associated with higher relapse rates. Pretransplant CSF assessment has low yield in detecting new CNS disease pretransplant in AML.

Laying the foundation for genomically-based risk assessment in chronic myeloid leukemia.

Outcomes for patients with chronic myeloid leukemia (CML) have substantially improved due to advances in drug development and rational treatment intervention strategies. Despite these significant advances there are still unanswered questions on patient management regarding how to more reliably predict treatment failure at the time of diagnosis and how to select frontline tyrosine kinase inhibitor (TKI) therapy for optimal outcome. The BCR-ABL1 transcript level at diagnosis has no established prognostic impact and cannot guide frontline TKI selection. BCR-ABL1 mutations are detected in ~50% of TKI resistant patients but are rarely responsible for primary resistance. Other resistance mechanisms are largely uncharacterized and there are no other routine molecular testing strategies to facilitate the evaluation and further stratification of TKI resistance. Advances in next-generation sequencing technology has aided the management of a growing number of other malignancies, enabling the incorporation of somatic mutation profiles in diagnosis, classification, and prognostication. A largely unexplored area in CML research is whether expanded genomic analysis at diagnosis, resistance, and disease transformation can enhance patient management decisions, as has occurred for other cancers. The aim of this article is to review publications that reported mutated cancer-associated genes in CML patients at various disease phases. We discuss the frequency and type of such variants at initial diagnosis and at the time of treatment failure and transformation. Current limitations in the evaluation of mutants and recommendations for future reporting are outlined. The collective evaluation of mutational studies over more than a decade suggests a limited set of cancer-associated genes are indeed recurrently mutated in CML and some at a relatively high frequency. Genomic studies have the potential to lay the foundation for improved diagnostic risk classification according to clinical and genomic risk, and to enable more precise early identification of TKI resistance.

Current Burden of Gunshot Wound Injuries at Two Los Angeles County Level I Trauma Centers.

BACKGROUND: Gunshot wound (GSW) injuries present a unique surgical challenge. This study explored the financial and clinical burdens of GSW patients across 2 Los Angeles County Level I trauma centers over the last 12 years, and compared them with other forms of interpersonal injury (OIPI). STUDY DESIGN: This was a retrospective study of patients presenting as those with GSW and OIPI (defined as combined stab wound or blunt assault), between January 1, 2006 and March 30, 2018, at LAC+USC Medical Center (LAC+USC) and Harbor UCLA Medical Center (HUCLA). Demographic and clinical variables were assessed for GSW patients and compared with victims of OIPI. RESULTS: There were 17,871 patients who met inclusion criteria. There was a significant difference in mortality for patients with GSW vs OIPI (11% vs 2%, p < 0.001). The odds ratio for GSW patients requiring operation was twice as high as those suffering OIPI (odds ratio [OR] 2.0, 95% CI 1.8 to 2.2). The odds ratio for GSW patients requiring ICU admission was 20% higher than that for OIPI patients (OR 1.23, 95% CI 1.11 to 1.36). Gunshot wound patients experienced a longer median length of stay vs OIPI patients (3 days vs 2 days, p < 0.001). The median hospital charge per admission for GSW was twice that of OIPI (GSW $12,612 vs OIPI $6,195; p < 0.001). CONCLUSIONS: When compared with OIPI, GSW patients arrived more severely injured and required more operations, more ICU admissions, and longer hospital stays. Patients with GSW incurred significantly higher hospital charges and had a significantly higher mortality rate. Gunshot wound injury is a unique public health concern requiring comprehensive, nation-wide, contemporary study.

Mobilization of Leukemic Cells Using Plerixafor as Part of a Myeloablative Preparative Regimen for Patients with Acute Myelogenous Leukemia Undergoing Allografting: Assessment of Safety and Tolerability.

Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for acute myelogenous leukemia (AML); however, a major cause of treatment failure is disease relapse. The purpose of this single-center Phase I study was to determine the safety and tolerability of administration of the CXCR4 inhibitor plerixafor (Mozobil; Sanofi Genzyme) along with myeloablative conditioning in patients with AML undergoing allogeneic HCT. The rationale was that plerixafor may mobilize leukemic stem cells, making them more susceptible to the conditioning chemotherapy (registered at ClinicalTrials.gov; identifier NCT01141543). Three patients were enrolled into each of 4 sequential cohorts (12 patients total). Patients in the first cohort received 1 dose of plerixafor (240 µg/kg s.c.) before the first dose of fludarabine and busulfan, and subsequent cohorts received injections before 2, 3, and 4 days of conditioning chemotherapy. The median age at HCT was 49 years (range, 38 to 58 years). All patients engrafted following HCT, with an absolute neutrophil count ≥.5 × 109/L observed at a median of 14 days (range, 11 to 18 days). Adverse events possibly related to plerixafor were transient and not severe. Main adverse events following the injection were nausea and dizziness in 4 patients (33%) and fatigue in 4 patients (33%). Among the 12 patients, 2 patients (17%) relapsed post-HCT and 6 (50%) were alive at the last follow-up. The median follow-up of survivors was 67 months (range, 53 to 82 months). In conclusion, plerixafor administration is safe and well tolerated when included in a myeloablative conditioning regimen for allogeneic HCT for AML. Further study in a larger cohort is warranted for the investigation of the impact of plerixafor on post-allogeneic HCT outcomes.

Can Deficiencies in Performance Be Identified Earlier in Surgical Residency? An Initial Report of a Surgical Trainee Assessment of Readiness Exam.

OBJECTIVE: Identifying gaps in medical knowledge, patient management, and procedural competence is difficult early in surgical residency. We designed and implemented an end-of-year examination for our postgraduate year 1 residents, entitled Surgical Trainee Assessment of Readiness (STAR). Our objective in this study was to determine whether STAR scores correlated with other available indicators of resident performance, such as the American Board of Surgery in-training exam (ABSITE) and Milestone scores, and if they provided evidence of additional discriminatory value. STUDY DESIGN: Overall and component scores of the STAR exam were compared to the ABSITE and Milestone assessment scores for the 17 categorical residents that took the exam in 2016 and 2017. SETTING: Harbor-UCLA Medical Center, a university-affiliated academic medical center. PARTICIPANTS: Seventeen categorical general surgery residents. RESULTS: The STAR Total Test Score (ß = 2.77, p = 0.006) was an independent predictor of the ABSITE taken the same year, and components of the STAR were independent predictors of ABSITE taken the following year. The STAR Total Test Score was lowest in the 3 residents who had at least 1 low Milestone score assessed in the same year; and 2 of these 3 residents had at least 1 low Milestone score assigned the next year after STAR. Lastly, the Patient Care 1 and 2 Milestones assessed in the same year as STAR were uniformly scored as appropriate for level of training, yet the corresponding STAR component for those milestones demonstrated 3 residents as having deficiencies. CONCLUSIONS: We have created a multifaceted standardized STAR exam, which correlates with performance on the ABSITE and early milestone scores. It also appears to discriminate resident performance where milestone assessments do not. Further evaluation of the STAR exam with longer term follow-up is needed to confirm these initial findings.

Assessment of a new genomic classification system in acute myeloid leukemia with a normal karyotype.

This study was performed to assess if a recently recommended genomic classification is predictive in patients with normal-karyotype (NK) acute myeloid leukemia (AML). A total of 393 patients were included. Analysis of genetic mutations was performed using targeted resequencing with an Illumina Hiseq 2000. We identified driver mutations across 40 genes, with one or more driver mutations identified in 95.7% of patients. The molecular subclassification was as follows: 34.6% patients (n = 136) with AML with the NPM1 mutation, 10.7% (n = 42) with AML with mutated chromatin or RNA-splicing genes or both, 1.5% (n = 6) with AML with TP53 mutations, 13.5% (n = 53) with AML with biallelic CEBPA mutations, 2.0% (n = 8) with AML with IDH2-R172 mutations and no other class-defining lesion, 29.5% (n = 116) with AML with driver mutations but no detected class-defining lesion, 4.3% (n = 17) with AML with no detected driver mutation, and 3.8% (n = 15) patients with AML who met the criteria for ≥2 genomic subgroups. The 5-year overall survival and relapse rate of subgroup in AML with mutated chromatin, RNA-splicing genes, or both was 11.6% (95% CI = 1.4-21.8%) and 71.4% (95% CI = 45.7-86.5%), respectively. This study suggests that the recently recommended genomic classification is an appropriate and replicable categorization system in the NK AML population. The subgroup of AML with mutated chromatin, RNA-splicing genes, or both showed extremely poor survival in NK-AML; thus, a novel approach is needed to improve their prognosis.

Monitoring modalities and assessment of fluid status: A practice management guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: Fluid administration in critically ill surgical patients must be closely monitored to avoid complications. Resuscitation guided by invasive methods are not consistently associated with improved outcomes. As such, there has been increased use of focused ultrasound and Arterial Pulse Waveform Analysis (APWA) to monitor and aid resuscitation. An assessment of these methods using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework is presented. METHODS: A subsection of the Surgical Critical Care Task Force of the Practice Management Guideline Committee of EAST conducted two systematic reviews to address the use of focused ultrasound and APWA in surgical patients being evaluated for shock. Six population, intervention, comparator, and outcome (PICO) questions were generated. Critical outcomes were prediction of fluid responsiveness, reductions in organ failures or complications and mortality. Forest plots were generated for summary data and GRADE methodology was used to assess for quality of the evidence. Reviews are registered in PROSPERO, the International Prospective Register of Systematic Reviews (42015032402 and 42015032530). RESULTS: Twelve focused ultrasound studies and 20 APWA investigations met inclusion criteria. The appropriateness of focused ultrasound or APWA-based protocols to predict fluid responsiveness varied widely by study groups. Results were mixed in the one focused ultrasound study and 9 APWA studies addressing reductions in organ failures or complications. There was no mortality advantage of either modality versus standard care. Quality of the evidence was considered very low to low across all PICO questions. CONCLUSION: Focused ultrasound and APWA compare favorably to standard methods of evaluation but only in specific clinical settings. Therefore, conditional recommendations are made for the use of these modalities in surgical patients being evaluated for shock. LEVEL OF EVIDENCE: Systematic Review, level II.

Misdiagnosing adult appendicitis: clinical, cost, and socioeconomic implications of negative appendectomy.

BACKGROUND: The aim of this study was to evaluate the clinical, financial, and socioeconomic factors associated with negative appendectomy (NA). METHODS: Data were obtained from the California State Inpatient Database (2005 to 2011). Patients (≥18 years) who underwent nonincidental appendectomies (n = 180,958) were evaluated with multivariate regression analyses. RESULTS: NA rates decreased from 4.5% in 2005 to 2.8% in 2011 (P < .01). Compared with patients with nonperforated appendicitis, NA was associated with longer length of stay, higher morbidity, and higher hospital costs. Multivariate regression demonstrated that African Americans, younger age (18 to 29 years), and females were predictors of NA. Hispanics and patients with public or no insurance were associated with a lower NA rate; however, perforation rates were higher. CONCLUSIONS: NA was associated with higher cost, longer length of stay, and higher morbidity compared with nonperforated appendicitis. Lower NA rates but higher perforation rates in some populations suggest a delay in presentation. Further research is needed to understand these disparities and to improve quality of care among low-income minority patients.

Transcatheter Versus Surgical Closure of Atrial Septal Defects in Children: A Value Comparison.

OBJECTIVES: The purpose of this study was to determine whether a transcatheter procedure or surgical closure offers a better value proposition for atrial septal defect (ASD) closure. BACKGROUND: Secundum ASDs are common congenital heart defects with both transcatheter and surgical treatment options. Although both options have been shown to have excellent results in children, the relative value of the 2 procedures is unclear. METHODS: Using data from the Pediatric Hospital Information System for 2004 to 2012, we compared the value of transcatheter versus surgical ASD closure for children ages 1 to 17 years, with value being defined as outcomes relative to costs. Total charges for procedure-related encounters were converted to costs using hospital-specific cost-to-charge ratios, and all costs were adjusted for inflation to reflect 2012 dollars. RESULTS: There were 4,606 transcatheter procedures and 3,159 surgeries at 35 children's hospitals. Those undergoing transcatheter closure were more likely to be older (5.6 years vs. 4.5 years, p < 0.0001). There was no mortality in either group. Children with a surgical procedure had a longer length of stay (4.0 days vs. 1.5 days, p < 0.0001), were more likely to have an infection (odds ratio: 3.73, p < 0.0001) or procedural complication (odds ratio: 6.66, p < 0.0001). Costs for transcatheter procedure encounters were lower than costs for surgical encounters (mean of $19,128 vs. $25,359, p < 0.0001). CONCLUSIONS: Both transcatheter and surgical ASD closure had excellent short-term outcomes, but transcatheter procedures had lower lengths of stay, rates of infection, and complications, resulting in lower overall costs. For children who are eligible, transcatheter ASD closure provides better short-term value than surgery.