Optimal Prone Position Duration in Patients With ARDS Due to COVID-19: The Omelette Pilot Trial.

BACKGROUND: Prone position (PP) has been widely used in the COVID-19 pandemic for ARDS management. However, the optimal length of a PP session is still controversial. This study aimed to evaluate the effects of prolonged versus standard PP duration in subjects with ARDS due to COVID-19. METHODS: This was a single-center, randomized controlled, parallel, and open pilot trial including adult subjects diagnosed with severe ARDS due to COVID-19 receiving invasive mechanical ventilation that met criteria for PP between March-September 2021. Subjects were randomized to the intervention group of prolonged PP (48 h) versus the standard of care PP (∼16 h). The primary outcome variable for the trial was ventilator-free days (VFDs) to day 28. RESULTS: We enrolled 60 subjects. VFDs were not significantly different in the standard PP group (18 [interquartile range [IQR] 0-23] VFDs vs 7.5 [IQR 0-19.0] VFDs; difference, -10.5 (95% CI -3.5 to 19.0, P = .08). Prolonged PP was associated with longer time to successful extubation in survivors (13.00 [IQR 8.75-26.00] d vs 8.00 [IQR 5.00-10.25] d; difference, 5 [95% CI 0-15], P = .001). Prolonged PP was also significantly associated with longer ICU stay (18.5 [IQR 11.8-25.3] d vs 11.50 [IQR 7.75-25.00] d, P = .050) and extended administration of neuromuscular blockers (12.50 [IQR 5.75-20.00] d vs 5.0 [IQR 2.0-14.5] d, P = .005). Prolonged PP was associated with significant muscular impairment according to lower Medical Research Council values (59.6 [IQR 59.1-60.0] vs 56.5 [IQR 54.1-58.9], P = .02). CONCLUSIONS: Among subjects with severe ARDS due to COVID-19, there was no difference in 28-d VFDs between prolonged and standard PP strategy. However, prolonged PP was associated with a longer ICU stay, increased use of neuromuscular blockers, and greater muscular impairment. This suggests that prolonged PP is not superior to the current recommended standard of care.

Impact of a Hospitalist Co-Management Program on Medical Complications and Length of Stay in Neurosurgical Patients.

BACKGROUND: The impact of co-management on clinical outcomes in neurosurgical patients is uncertain. This study aims to describe the implementation of a hospitalist co-management program in a neurosurgery department and its impact on the incidence of complications, mortality, and length of stay. METHODS: The authors used a quasi-experimental study design that compared a historical control period (July-December 2017) to a prospective intervention arm. During the intervention period, patients admitted to a neurosurgery inpatient unit who were older than 65 years, suffered certain conditions, or were admitted from ICUs were included in the co-management program. Two hospitalists joined the surgical staff and intervened in the diagnostic and therapeutical plan of patients, participating in clinical decisions and coordinating patient navigation with neurosurgeons. The incidence of moderate or severe complications measured by the Accordion Severity Grading System, in-hospital mortality, and length of stay of the two cohorts were compared. Multivariate regression was used to adjust for confounders, and the average treatment effect was estimated using inverse probability of treatment weighting. RESULTS: The adjusted incidence of moderate or severe complications was lower among co-managed patients (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.39-0.91). Mortality was unchanged (OR 0.83, 95% CI 0.15-4.17). Length of stay was lower in co-managed patients, with a 1.3-day reduction observed after inverse probability of treatment weighting analysis. CONCLUSION: Hospitalist co-management was associated with a reduced incidence of complications and length of stay in neurosurgical patients, but there was no difference in in-hospital mortality.

Shock Index and Physiological Stress Index for reestratifying patients with intermediate-high risk pulmonary embolism.

OBJECTIVE: Study and Evaluation of Two Scores: Shock Index (SI) and Physiological Stress Index (PSI) as discriminators for proactive treatment (reperfusion before decompensated shock) in a population of intermediate-high risk pulmonary embolism (PE). DESIGN: Using a database from a retrospective cohort with clinical variables and the outcome variable of "proactive treatment", a comparison of the populations was conducted. Optimal cut-off for "proactive treatment" points were obtained according to the SI and PSI. Comparisons were carried out based on the cut-off points of both indices. SETTING: Patients admitted to a mixed ICU for PE. PARTICIPANTS: Patients >18 years old admitted to the ICU with intermediate-high risk PE recruited from January 2015 to October 2022. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Population comparison and metrics regarding predictive capacity when determining proactive treatment. RESULTS: SI and PSI independently have a substandard predictive capacity for discriminating patients who may benefit from an early reperfusion therapy. However, their combined use improves detection of sicker intermediate-high risk PE patients (Sensitivity = 0.66) in whom an early reperfusion therapy may improve outcomes (Specificity = 0.9). CONCLUSIONS: The use of the SI and PSI in patients with intermediate-high risk PE could be useful for selecting patients who would benefit from proactive treatment.

Postoperative Blood Pressure Deficit and Acute Kidney Injury After Liver Transplant.

OBJECTIVES: Acute kidney injury is a common cause of morbidity in liver transplant recipients. In critically ill patients who received an orthotopic liver transplant, we examined whether those with acute kidney injury had a greater deficit between pretransplant and posttransplant hemodynamic pressure-related parameters compared with those without acute kidney injury in the early postoperative period. MATERIALS AND METHODS: We included patients who underwent an orthotopic liver transplant during the study period. We obtained premorbid and intensive care unit time-weighted average values for hemodynamic pressure-related parameters (systolic, diastolic, and mean arterial pressure; central venous pressure; mean perfusion pressure; and diastolic perfusion pressure) and calculated deficits in those values. We defined acute kidney injury progression as an increase of ≥1 Kidney Disease: Improving Global Outcomes stage. RESULTS: We included 150 eligible transplantrecipients, with 88 (59%) having acute kidney injury progression. Acute kidney injury was associated with worse clinical outcomes. All achieved pressure-related values were similar between transplant recipients with or without acute kidney injury progression. However, those with acute kidney injury versus those without progression had greater diastolic perfusion pressure deficit at 12 hours (-8.33% vs 1.93%; P = .037) and 24 hours (-7.38% vs 5.11%; P = .002) and increased central venous pressure at 24 hours (46.13% vs 15%; P = .043) and 48 hours (40% vs 20.87%; P = .039). CONCLUSIONS: Patients with acute kidney injury progression had a greater diastolic perfusion pressure deficit and increased central venous pressure compared with patients without progression. Such deficits might be modifiable risk factors for the prevention of acute kidney injury progression.

ABO Blood System and COVID-19 Susceptibility: Anti-A and Anti-B Antibodies Are the Key Points.

The implication of the ABO blood group in COVID-19 disease was formulated early, at the beginning of the COVID-19 pandemic more than 2 years ago. It has now been established that the A blood group is associated with more susceptibility and severe symptoms of COVID-19, while the O blood group shows protection against viral infection. In this review, we summarize the underlying pathophysiology of ABO blood groups and COVID-19 to explain the molecular aspects behind the protective mechanism in the O blood group. A or B antigens are not associated with a different risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than that of other antigens. In this case, the cornerstone is natural anti-A and anti-B antibodies from the ABO system. They are capable of interfering with the S protein (SARS-CoV-2) and angiotensin-converting enzyme 2 (ACE2; host cell receptor), thereby conferring protection to patients with sufficient antibodies (O blood group). Indeed, the titers of natural antibodies and the IgG isotype (specific to the O blood group) may be determinants of susceptibility and severity. Moreover, older adults are associated with a higher risk of bad outcomes due to the lack of antibodies and the upregulation of ACE2 expression during senescence. A better understanding of the role of the molecular mechanism of ABO blood groups in COVID-19 facilitates better prognostic stratification of the disease. Furthermore, it could represent an opportunity for new therapeutic strategies.

Plasmapheresis in the Treatment of Refractory Myoclonic Status. A Case Report.

A case of myoclonic status treated with plasmapheresis in a patient of 63 years of age who was admitted to a Spanish intensive care unit is reported. The patient showed clinical and radiological evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; molecular tests did not verify this.

Can the Cytokine Profile According to ABO Blood Groups Be Related to Worse Outcome in COVID-19 Patients? Yes, They Can.

Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank: p = 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064-8.665), p < 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540-50.878), p = 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.

Combination of arterial lactate levels and Cv-aCO2/Da-vO2 ratio to predict early allograft dysfunction after liver transplantation.

PURPOSE: We examined the ability of the P(v-a)CO2/Da-vO2 ratio combined with elevated lactate levels to predict early allograft dysfunction (EAD). MATERIALS AND METHODS: Patients were classified into four groups according to lactate levels and P(v-a)CO2/Da-vO2 ratio: Group 1; lactate >2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio >1.0; Group 2; lactate >2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio <1.0; group 3; lactate<2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio >1.0; group 4; lactate<2.0 mmol/L and P(v-a)CO2/Da-vO2 ratio <1.0. We defined EAD according to Olthoff criteria. RESULTS: One-hundred and fifty patients were included. EAD occurred in 41 patients (27.3%), and was associated with worse graft survival at 1 year (92% vs. 73%; P = ,003) as well as a higher re-transplantation rate (4,6% vs. 17,1%; P = ,019). The multivariate analysis revealed that P(v-a)CO2/Da-vO2 ratio at T6 [OR 7.05(CI95% 2.77-19.01, P<.001)] was an independent predictor for EAD. Belonging to group 1 at 6 h was associated with worse clinical outcomes but no association was found with 1-year graft survival or 1-year patient survival. CONCLUSIONS: In this single center, prospective, observational study in patients who received an OLT, we found that elevated lactate levels combined with a high Cv-aCO2/Da-vO2 after 6 h was associated with the development of EAD and worse clinical outcomes in the early postoperative period.

Evaluation of Cytokines as Robust Diagnostic Biomarkers for COVID-19 Detection.

Antigen tests or polymerase chain reaction (PCR) amplification are currently COVID-19 diagnostic tools. However, developing complementary diagnosis tools is mandatory. Thus, we performed a plasma cytokine array in COVID-19 patients to identify novel diagnostic biomarkers. A discovery-validation study in two independent prospective cohorts was performed. The discovery cohort included 136 COVID-19 and non-COVID-19 patients recruited consecutively from 24 March to 11 April 2020. Forty-five cytokines' quantification by the MAGPIX system (Luminex Corp., Austin, TX, USA) was performed in plasma samples. The validation cohort included 117 patients recruited consecutively from 15 to 25 April 2020 for validating results by ELISA. COVID-19 patients showed different levels of multiple cytokines compared to non-COVID-19 patients. A single chemokine, IP-10, accurately identified COVID-19 patients who required hospital admission (AUC: 0.962; 95%CI (0.933-0.992); p < 0.001)). The results were validated in an independent cohort by multivariable analysis (OR: 25.573; 95%CI (8.127-80.469); p < 0.001) and AUROC (AUC: 0.900; 95%CI (0.846-0.954); p < 0.001). Moreover, showing IP-10 plasma levels over 173.35 pg/mL identified COVID-19 with higher sensitivity (86.20%) than the first SARS-CoV-2 PCR. Our discover-validation study identified IP-10 as a robust biomarker in clinical practice for COVID-19 diagnosis at hospital. Therefore, IP-10 could be used as a complementary tool in clinical practice, especially in emergency departments.

HGF, IL-1α, and IL-27 Are Robust Biomarkers in Early Severity Stratification of COVID-19 Patients.

Pneumonia is the leading cause of hospital admission and mortality in coronavirus disease 2019 (COVID-19). We aimed to identify the cytokines responsible for lung damage and mortality. We prospectively recruited 108 COVID-19 patients between March and April 2020 and divided them into four groups according to the severity of respiratory symptoms. Twenty-eight healthy volunteers were used for normalization of the results. Multiple cytokines showed statistically significant differences between mild and critical patients. High HGF levels were associated with the critical group (OR = 3.51; p < 0.001; 95%CI = 1.95-6.33). Moreover, high IL-1α (OR = 1.36; p = 0.01; 95%CI = 1.07-1.73) and low IL-27 (OR = 0.58; p < 0.005; 95%CI = 0.39-0.85) greatly increased the risk of ending up in the severe group. This model was especially sensitive in order to predict critical status (AUC = 0.794; specificity = 69.74%; sensitivity = 81.25%). Furthermore, high levels of HGF and IL-1α showed significant results in the survival analysis (p = 0.033 and p = 0.011, respectively). HGF, IL-1α, and IL 27 at hospital admission were strongly associated with severe/critical COVID-19 patients and therefore are excellent predictors of bad prognosis. HGF and IL-1α were also mortality biomarkers.

Comprehensive Custom NGS Panel Validation for the Improvement of the Stratification of B-Acute Lymphoblastic Leukemia Patients.

BACKGROUND: B-acute lymphoblastic leukemia (B-ALL) is a hematological neoplasm of the stem lymphoid cell of the B lineage, characterized by the presence of genetic alterations closely related to the course of the disease. The number of alterations identified in these patients grows as studies of the disease progress, but in clinical practice, the conventional techniques frequently used are only capable of detecting the most common alterations. However, techniques, such as next-generation sequencing (NGS), are being implemented to detect a wide spectrum of new alterations that also include point mutations. METHODS: In this study, we designed and validated a comprehensive custom NGS panel to detect the main genetic alterations present in the disease in a single step. For this purpose, 75 B-ALL diagnosis samples from patients previously characterized by standard-of-care diagnostic techniques were sequenced. RESULTS: The use of the custom NGS panel allowed the correct detection of the main genetic alterations present in B-ALL patients, including the presence of an aneuploid clone in 14 of the samples and some of the recurrent fusion genes in 35 of the samples. The panel was also able to successfully detect a number of secondary alterations, such as single nucleotide variants (SNVs) and copy number variations (CNVs) in 66 and 46 of the samples analyzed, respectively, allowing for further refinement of the stratification of patients. The custom NGS panel could also detect alterations with a high level of sensitivity and reproducibility when the findings obtained by NGS were compared with those obtained from other conventional techniques. CONCLUSIONS: The use of this custom NGS panel allows us to quickly and efficiently detect the main genetic alterations present in B-ALL patients in a single assay (SNVs and insertions/deletions (INDELs), recurrent fusion genes, CNVs, aneuploidies, and single nucleotide polymorphisms (SNPs) associated with pharmacogenetics). The application of this panel would thus allow us to speed up and simplify the molecular diagnosis of patients, helping patient stratification and management.

Risk factors and outcome of COVID-19 in patients with hematological malignancies.

BACKGROUND: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined. PATIENTS AND METHODS: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. RESULTS: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p = 0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age > 70 years [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.8, p = 0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p < 0.0001); ECOG 3-4 (OR, 2.56, 95% CI 1.4-4.7, p = 0.003); neutropenia (< 0.5 × 109/L) (OR 2.8, 95% CI 1.3-6.1, p = 0.01); and a C-reactive protein (CRP) > 20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p < 0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p = 0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P = 0.1). CONCLUSIONS: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19.

Aplicación de la nueva definición Sepsis-3 en una cohorte de pacientes con sepsis grave y shock séptico ingresados en unidad de cuidados intensivos desde el Servicio de Urgencias / Application of the new Sepsis-3 definition in a cohort of patients with severe sepsis and septic shock admitted to Intensive Care Unit from the Emergency Department

Antecedentes y objetivo: Tras la publicación de la nueva definición de sepsis y shock séptico, nuestro objetivo es analizar la evolución de los pacientes que ingresan en UCI por enfermedad infecciosa utilizando la definición clásica y los nuevos criterios. Material y métodos: Subanálisis de un estudio observacional y prospectivo. Incluye a 98 pacientes ingresados en UCI por enfermedad infecciosa desde Urgencias durante 18 meses. Se estudió la evolución clínica en UCI y la mortalidad hospitalaria. Resultados: El 78% de los pacientes tuvieron shock séptico con la definición Sepsis-2 y el 52% con los criterios Sepsis-3. La mortalidad hospitalaria fue del 29 y del 41%, respectivamente. El RR de mortalidad hospitalaria de los pacientes con shock séptico fue 10,3 (IC 95%: 2,8-37,5) respecto a los pacientes sin shock. La probabilidad de supervivencia a los 30 días de los pacientes con sepsis y shock séptico fue del 78 y 68%, respectivamente (long Rank < 0,001). Conclusiones: En nuestra experiencia, la incorporación de la puntuación SOFA y el lactato a la nueva definición puede mejorar la valoración del riesgo de muerte hospitalaria

Background and objectives: After the publication of the new definition for sepsis and septic shock, our objective is to analyse the evolution of patients admitted to ICU with an infection process using the previous and new recommendations. Materials and methods: This is a sub-analysis of a previous observational prospective study. We included 98 patients admitted to ICU from the emergency department due to infection during an 18-month period. We studied the clinical evolution during ICU admission and hospital mortality. Results: According to Sepsis-2 definition, 78% percent had septic shock and using Sepsis-3 criteria, 52%; hospital mortality was 29 and 41%, respectively. The RR of hospital mortality of septic shock was 10.3 (95% CI: 2.8-37.5) compared to patients without shock. The 30-day probability survival of patients with sepsis and septic shock were 78% and 68%, respectively (long rank < 0.001). Conclusions: In our experience, the incorporation of the SOFA score and lactate levels to the new definition could help improve the evaluation of risk of hospital death

Application of the new Sepsis-3 definition in a cohort of patients with severe sepsis and septic shock admitted to Intensive Care Unit from the Emergency Department. / Aplicación de la nueva definición Sepsis-3 en una cohorte de pacientes con sepsis grave y shock séptico ingresados en unidad de cuidados intensivos desde el Servicio de Urgencias.

BACKGROUND AND OBJECTIVES: After the publication of the new definition for sepsis and septic shock, our objective is to analyse the evolution of patients admitted to ICU with an infection process using the previous and new recommendations. MATERIALS AND METHODS: This is a sub-analysis of a previous observational prospective study. We included 98 patients admitted to ICU from the emergency department due to infection during an 18-month period. We studied the clinical evolution during ICU admission and hospital mortality. RESULTS: According to Sepsis-2 definition, 78% percent had septic shock and using Sepsis-3 criteria, 52%; hospital mortality was 29 and 41%, respectively. The RR of hospital mortality of septic shock was 10.3 (95% CI: 2.8-37.5) compared to patients without shock. The 30-day probability survival of patients with sepsis and septic shock were 78% and 68%, respectively (long rank < 0.001). CONCLUSIONS: In our experience, the incorporation of the SOFA score and lactate levels to the new definition could help improve the evaluation of risk of hospital death.

Utility of SOFA and Δ-SOFA scores for predicting outcome in critically ill patients from the emergency department.

OBJECTIVE: The condition of critically ill patients in the emergency department (ED) varies from moment to moment. The aims of this study are to quantify sequential organ failure assessment (SOFA) and changes in SOFA scores over time and determine its prognostic impact. PATIENTS AND METHODS: This is a prospective observational cohort study. We included 269 patients consecutively admitted to the ICU from the ED over 18 months. The SOFA scores at ED admission (ED-SOFA) and ICU admission (ICU-SOFA) were obtained. Relative changes in SOFA scores were calculated as follows: Δ-SOFA=ICU-SOFA-ED-SOFA. Patients were divided into two groups depending on the Δ-SOFA score: (a) Δ-SOFA=0-1; and (b) Δ-SOFA more than or equal to 2. RESULTS: The median ED-SOFA score was two points (interquartile range: 1-4.5) and the Δ-SOFA score was 2 points (interquartile range: 0-3). The Δ-SOFA score was more powerful (area under the curve: 0.81) than the ED-SOFA score (area under the curve: 0.75) in predicting hospital mortality. Sixteen (6%) patients had a Δ-SOFA score less than 0, 116 (43%) patients had a Δ-SOFA=0-1, and 137 (51%) patients had a Δ-SOFA of at least 2 points. The probability of being alive at hospital discharge was 51 and 86.5% in Δ-SOFA of at least 2 and Δ-SOFA=0-1 groups, respectively (P<0.001). Risk factors for an increase of two or more SOFA points were age, cirrhosis, a diagnosis of sepsis, and a prolonged ED stay. CONCLUSION: SOFA and changes in the SOFA score over time are potentially useful tools for risk stratification when applied to critically ill patients admitted to ICUs from the ED.

Genome-Wide DNA Copy Number Analysis of Acute Lymphoblastic Leukemia Identifies New Genetic Markers Associated with Clinical Outcome.

UNLABELLED: Identifying additional genetic alterations associated with poor prognosis in acute lymphoblastic leukemia (ALL) is still a challenge. AIMS: To characterize the presence of additional DNA copy number alterations (CNAs) in children and adults with ALL by whole-genome oligonucleotide array (aCGH) analysis, and to identify their associations with clinical features and outcome. Array-CGH was carried out in 265 newly diagnosed ALLs (142 children and 123 adults). The NimbleGen CGH 12x135K array (Roche) was used to analyze genetic gains and losses. CNAs were analyzed with GISTIC and aCGHweb software. Clinical and biological variables were analyzed. Three of the patients showed chromothripsis (cth6, cth14q and cth15q). CNAs were associated with age, phenotype, genetic subtype and overall survival (OS). In the whole cohort of children, the losses on 14q32.33 (p = 0.019) and 15q13.2 (p = 0.04) were related to shorter OS. In the group of children without good- or poor-risk cytogenetics, the gain on 1p36.11 was a prognostic marker independently associated with shorter OS. In adults, the gains on 19q13.2 (p = 0.001) and Xp21.1 (p = 0.029), and the loss of 17p (p = 0.014) were independent markers of poor prognosis with respect to OS. In summary, CNAs are frequent in ALL and are associated with clinical parameters and survival. Genome-wide DNA copy number analysis allows the identification of genetic markers that predict clinical outcome, suggesting that detection of these genetic lesions will be useful in the management of patients newly diagnosed with ALL.