Predictors Of Good Outcome Research Articles

Lung ultrasound score predicts outcomes in patients with acute respiratory failure secondary to COVID-19 treated with non-invasive respiratory support: a prospective cohort study

BackgroundLung ultrasound has demonstrated its usefulness in several respiratory diseases management. One derived score, the Lung Ultrasound (LUS) score, is considered a good outcome predictor in patients with Acute Respiratory Failure (ARF). Nevertheless, it has not been tested in patients undergoing non-invasive respiratory support (NIRS). Taking this into account, the aim of this study is to evaluate LUS score as a predictor of 90-day mortality, ETI (Endotracheal intubation) and HFNC (High Flow Nasal Cannula) failure in patients with ARF due to COVID-19 admitted to a Respiratory Intermediate Care Unit (RICU) for NIRS management.ResultsOne hundred one patients were admitted to the RICU during the study period. Among these 76% were males and the median age was 55 (45–64) years. Initial ARF management started with HFNC, the next step was the use of Continuous Positive Airway Pressure (CPAP) devices and the last intervention was ETI and Intensive Care Unit (ICU) admission. Of the total study population, CPAP was required in 40%, ETI in 26%, while 15% died. By means of a ROC analysis, a LUS ≥ 25 points was identified as the cut-off point for mortality(AUC 0.81, OR 1.40, 95% CI 1.14 to 1.71; p < 0.001), ETI (AUC 0.83, OR 1.43, 95% CI 1.20 to 1.70; p < 0.001) and HFNC failure (AUC 0.75, OR 1.25, 95% CI 1.12 to 1.41; p < 0.001). Kaplan-Meier survival curves also identified LUS ≥ 25 as a predictor of 90-days mortality (HR 4.16, 95% CI 1.27–13.6) and 30 days ETI as well.ConclusionIn our study, a ≥ 25 point cut-off of the Lung Ultrasound Score was identified as a good outcome prediction factor for 90-days mortality, ETI and HFNC failure in a COVID-19 ARF patients cohort treated in a RICU. Considering that LUS score is easy to calculate, a multicenter study to confirm our findings should be performed.

DNA methylation in long COVID

Long COVID (also termed Post-acute sequelae of COVID-19 [PASC]) refers to the chronic symptoms that survivors may experience after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute coronavirus disease 2019 (COVID-19) disease. Long COVID represents a global public health, medical, and nursing challenge that affects millions of people. As an emerging and evolving syndrome, long COVID manifests with many combinations of clinical signs and symptoms that healthcare providers and scientists are cataloging and struggling to understand. In this mini-review, we introduce the epigenetic battlefield of DNA methylation (DNAm) on which the virus and the host interact. We suggest ways in which DNAm phenomena and markers induced by this virus-host interaction may help clarify the pathology and prognosis of long COVID. Knowledge of DNAm characteristics of long COVID patients is limited as of this writing (early-2024), investigators have noted both the partial reversibility and the potential long-lasting persistence of the DNAm markers induced by acute COVID-19. Long-term sequelae seen in other coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are potential references for long COVID in an effort towards more precise diagnosis and disease characterization, better prediction of outcomes, and the use of epigenetic phenomena towards development of new drugs and immunotherapies.

Pre-intervention myocardial stress is a good predictor of aortic valvoluplasty outcome for fetal critical aortic stenosis and evolving HLHS.

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) causes biomechanical and functional aberrations, leading to a high risk of progression to hypoplastic left heart syndrome (HLHS) at birth. Fetal aortic valvuloplasty (FAV) can resolve outflow obstruction and may reduce progression risk. However, it is currently difficult to accurately predict which patients will respond to the intervention and become functionally biventricular (BV) at birth, as opposed to becoming functionally univentricular (UV). This prediction is important for patient selection, parental counselling, and surgical planning. Therefore, we investigated whether biomechanics parameters from pre-FAV image-based computations could robustly distinguish between CAS-eHLHS cases with BV or UV outcomes in a retrospective cohort. To do so we performed image-based finite element biomechanics modelling of nine CAS-eHLHS cases undergoing intervention and six healthy fetal control hearts, and found that a biomechanical parameter, peak systolic myofibre stress, showed a uniquely large difference between BV and UV cases, which had a larger magnitude effect than echocardiography parameters. A simplified equation was derived for quick and easy estimation of myofibre stress from echo measurements via principal component analysis. When tested on a retrospective cohort of 37 CAS-eHLHS cases, the parameter outperformed other parameters in predicting UV versus BV outcomes, and thus has a high potential of improving outcome predictions, if incorporated into patient selection procedures. Physiologically, high myocardial stresses likely indicate a healthier myocardium that can withstand high stresses and resist pathological remodelling, which can explain why it is a good predictor of BV outcomes. KEY POINTS: Predicting the morphological birth outcomes (univentricular versus biventricular) of fetal aortic valvuloplasty for fetal aortic stenosis with evolving HLHS is important for accurate patient selection, parental counselling and management decisions. Computational simulations show that a biomechanics parameter, pre-intervention peak systolic myofibre stress, is uniquely robust in distinguishing between such outcomes, outperforming all echo parameters. An empirical equation was developed to quickly compute peak systolic myofibre stress from routine echo measurements and was the best predictor of outcomes among a wide range of parameters tested.

Abstract TMP76: Outcomes in Large Mostly Intraventricular Hemorrhage: From the Clear III Trial Public Use Dataset

Introduction: Intraventricular hemorrhage (IVH), a common complication of intracerebral hemorrhage (ICH), can occur with little or no associated ICH (mostly IVH, mIVH). mIVH is reported to have better outcomes than IVH associated with substantial ICH. Few data exist describing outcomes from mIVH, especially more severe cases. Hypothesis: Using the CLEAR III public use dataset, outcomes from large mIVH can be described and may be useful to providers and families making decisions about goals of care. Methods: Large mIVH was defined as CLEAR III patients with ICH volume &lt; 5 cc and IVH volume &gt; 30 cc. A backward stepwise logistic regression model identified baseline predictors of 180 day modified Rankin score 0-3 (good outcome), and a post-estimation probability was calculated for each patient. Descriptive nonparametric statistics are provided, including medians with interquartile range (IQR). Patients were divided into prognostic tertiles based on probability of a good outcome with corresponding 180 day modified Rankin scores (mRS) are displayed via a Sankey diagram. Results: Overall, 72/500 (14.4%) of CLEAR III patients had large mIVH. Among these 72, median (IQR) age was 59.5 (51-68) years, 39% were female, median (IQR) GCS 8 (6.5-10), IVH volume 48 cc (39-67) and 180 day mRS 4 (2-6). Age and IVH volume were final model independent predictors of good outcome. Baseline median (IQR) values for Age and IVH volume in each prognostic tertile with 180 day mRS distributions are shown in the Figure. Good outcome was possible despite large mIVH, especially with younger age and smaller IVH volumes. Conclusion: Focusing on the CLEAR III subset of patients with large mIVH, a simple regression model identified prognostic tertiles which combined with a Sankey diagram provide easily interpretable outcome distributions that may facilitate clinical decision-making.

Utility of Lean Body Mass Equations and Body Mass Index for Predicting Outcomes in Critically Ill Adults with Sepsis: A Retrospective Study.

Lean body mass is a significant component of survival from sepsis. Several equations can be used for calculating lean body mass based on age, sex, body weight, and height. We hypothesized that lean body mass is a better predictor of outcomes than the body mass index (BMI). This study used a multicenter cohort study database. The inclusion criteria were age ≥18 years and a diagnosis of sepsis or septic shock. BMI was classified into four categories: underweight (<18.5 kg/m2), normal (≥18.5-<25 kg/m2), overweight (≥25-<30 kg/m2), and obese (≥30 kg/m2). Four lean body mass equations were used and categorized on the basis of quartiles. The outcome was in-hospital mortality among different BMI and lean body mass groups. Among 85,558 patients, 3916 with sepsis were included in the analysis. Regarding BMI, in-hospital mortality was 36.9%, 29.8%, 26.7%, and 27.9% in patients who were underweight, normal weight, overweight, and obese, respectively (p < 0.01). High lean body mass did not show decreased mortality in all four equations. In critically ill patients with sepsis, BMI was a better predictor of in-hospital mortality than the lean body mass equation at intensive care unit (ICU) admission. To precisely predict in-hospital mortality, ICU-specific lean body mass equations are needed.

Neurological intervention transition model for dynamic prediction of good outcome in spontaneous subarachnoid haemorrhage.

Deterioration of neurovascular conditions can be rapid in patients with spontaneous subarachnoid haemorrhage (SAH) and often lead to poor clinical outcomes. Therefore, it is crucial to promptly assess and continually track the progression of the disease. This study incorporated baseline clinical conditions, repeatedly measured neurological grades and haematological biomarkers for dynamic outcome prediction in patients with spontaneous SAH. Neurological intervention, mainly aneurysm clipping and endovascular embolisation, was also incorporated as an intermediate event in developing a neurological intervention transition (NIT) joint model. A retrospective cohort study was performed on 701 patients in spontaneous SAH with a study period of 14days from the MIMIC-IV dataset. A dynamic prognostic model predicting outcome of patients was developed based on combination of Cox model and piecewise linear mixed-effect models to incorporate different types of prognostic information. Clinical baseline covariates, including cerebral oedema, cerebral infarction, respiratory failure, hydrocephalus and vasospasm, as well as repeated measured Glasgow Coma Scale (GCS), glucose and white blood cell (WBC) levels were covariates contributing to the optimal model. Incorporation of neurological intervention as an intermediate event increases the prediction performance compared with baseline joint modelling approach. The average AUC of the optimal model proposed in this study is 0.7783 across different starting points of prediction and prediction intervals. The model proposed in this study can provide dynamic prognosis for spontaneous SAH patients and significant potential benefits in critical care management.

Predictors of good outcomes and mortality after thrombectomy for basilar artery occlusion within 12 hours of onset.

Patients with acute basilar artery occlusion (ABAO) who undergo combined standard medical treatment (SMT) and endovascular thrombectomy (EVT) may still have unsatisfactory outcomes. This study was conducted to identify the factors that may impact their outcomes. We retrospectively reviewed the data of all patients with ABAO combined with SMT and EVT in the endovascular treatment for acute basilar artery occlusion (ATTENTION) trial. A good outcome is defined as a modified Rankin Scale (mRS) score of 0-3, a poor outcome as mRS score of 4-6, and mortality as death at 90-day follow-up. The study analyzed various factors influencing the patients' good outcomes and mortality. The study included 221 patients (148 men and 73 women). Among these patients, 45.7% achieved an mRS score of 0-3, while the overall mortality rate was 37.1% (82/221). A good outcome was significantly associated with younger age (adjusted OR 0.96; 95% CI 0.93 to 0.99; P=0.019), a baseline posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) of 8-10 (adjusted OR 2.34; 95% CI 1.07 to 5.12; P=0.034), and post-procedure pc-ASPECTS of 8-10 (adjusted OR 1.40; 95% CI 1.07 to 1.84; P=0.013). Additionally, time from puncture to reperfusion (adjusted OR 2.02; 95% CI 1.2 to 3.41; P=0.008) and intracranial hemorrhage (adjusted OR 3.59; 95% CI 1.09 to 11.8; P=0.035) were associated with 90-day mortality. Younger age, baseline pc-ASPECTS of 8-10, and higher post-procedure pc-ASPECTS could effectively predict good outcomes for patients with ABAO undergoing EVT. Additionally, a prolonged time from puncture to reperfusion and intracranial hemorrhage can independently predict mortality. NCT04751708.

Diagnostic Efficacy of SOFA Score in Predicting Outcome and Mortality: An ICU Experience from Pakistan

Objective: To determine the cut-off value of Sequential Organ Failure Assessment score at the time of admission in Intensive Care Unit to predict mortality and outcome in critically ill patients.&#x0D; Materials and Methods: This cross-sectional, descriptive study was undertaken at Intensive Care Unit of Rawalpindi Teaching Hospital, Rawalpindi, Pakistan between April and August 2023. SOFA score of all critically ill patients at the time of admission in ICU and their outcome (expired or discharged) was recorded. Receiver Operator Characteristics Curve (ROC) was drawn for SOFA score and mortality. Cut off value for SOFA score was calculated. Outcome of patients above and below the cut off value for SOFA score was studied using Chi-square test.&#x0D; Results: A total of 100 patients (54% females and 46% males) were included in the study with mean patient age of 68.93±11.09 years. Out of 100 patients, 48 (48%) improved and 52 (52%) expired. The Mean initial SOFA score was 5.44±3.99 in patients who improved and 9.91±4.20 in patients who expired. Coordinates of the ROC curve showed that SOFA score cut off value 7.5 had best corresponding sensitivity (0.777) and specificity (0.740). The patients were categorized to Group I (SOFA score ≤7), and Group II (SOFA score ≥8). 34.04% of the Group I and 75.47% of the Group II patients expired (p-value 0.0000001)&#x0D; Conclusions: Mortality was higher in patients who had higher SOFA score at the time of admission in Intensive Care Unit. At admission SOFA scores (≤7 and &gt;8) are best predictor of outcome in critically ill patients.

Complete responses in AL amyloidosis are unequal: the impact of free light chain mass spectrometry in AL amyloidosis

AbstractAmyloidogenic serum free light chains (sFLCs) drive disease progression in AL amyloidosis. Matrix-assisted laser desorption/ionization time of flight mass spectrometry–based FLC assay (FLC-MS) has greater sensitivity than conventional sFLC assays allowing for the detection of serological residual disease. We report the utility of FLC-MS in a large series of patients with AL amyloidosis assessing the impact of FLC-MS negativity after treatment on overall survival (OS) and organ response rates. Serum samples were analyzed using FLC-MS at diagnosis and at 6 and 12 months after treatment. The impact of FLC-MS negativity over standard hematologic responses on survival and organ response was assessed. A total of 487 patients were included; 290 (59%) and 349 (71.5%) had cardiac and renal involvement, respectively. There was 100% concordance between the light chain (LC) fibril type and LC isotype identified by FLC-MS. At 6 and 12 months, 81 (16.6%) and 101 (20.7%) were FLC-MS negative. Of those achieving a conventional hematologic complete response (CR) at 6 and 12 months, 45 (27.7%) and 64 (39%) were FLC-MS negative. At 12 months, median OS for CR + FLC-MS negative was not reached vs 108 months in CR + FLC-MS positive (P = .024). At 12 months, 70% of patients with FLC-MS negativity (vs 50% FLC-MS positive) achieved a cardiac response (P = .015). In a multivariate analysis, FLC-MS negativity at 12 months was an independent predictor of better outcomes. FLC-MS can detect persistent monoclonal light chains in a significant proportion of patients in a conventional hematologic CR. FLC-MS assessment promises to be a new standard for response assessment in AL amyloidosis.

Study of Treatment and Patient Factors of Hemoporfin‐Photodynamic Therapy for Port‐Wine Stains

Background. Port‐wine stains (PWS) affect a substantial number of people, and despite the use of pulsed dye laser as the gold standard therapy, some patients fail to respond, and new modalities are needed. Recently, hemoporfin‐photodynamic therapy (hemoporfin‐PDT) has shown good efficacy and safety in treating PWS, with increasing evidence. Objectives. To evaluate the efficacy and safety of hemoporfin‐PDT in the treatment of PWS and to analyze the factors that influence efficacy. Methods. The clinical data of 215 patients (79 men and 136 women aged 3–71 years) from a single center were retrospectively analyzed, out of which 173 were valid for efficacy analysis and 129 for safety analysis. Efficacy was rated as excellent (≥75% improvement), good (≥50% to &lt;75% improvement), fair (≥25% to &lt;50%), and poor (&lt;25% improvement) by two blinded dermatologists. The patient‐assessed efficacy was collected based on the aforementioned criteria using an electronic questionnaire. The association of efficacy with possible influential factors was investigated, namely, age, sex, history of previous treatment, combined scars caused by previous treatments, lesion site, lesion type, lesion size, degree of lip involvement, and number of hemoporfin‐PDT sessions. Adverse events were investigated to evaluate the safety profile. Results. Excellent, good, fair, and poor efficacy was achieved in 78 (45.1%), 38 (22.0%), 36 (20.8%), and 21 (12.1%) patients, respectively, after a variable number of sessions of hemoporfin‐PDT. More treatment sessions (p &lt; 0.001), age ≥18 years (p = 0.037), no previous treatments (p = 0.020), and head/neck location (p = 0.009) were associated with better outcomes. Pain, edema, exudation/crusting, and hyperpigmentation were common adverse events, with satisfactory recovery. Scarring occurred in 2.3% of the patients. Conclusions. For treating PWS with hemoporfin‐PDT, more treatment sessions and head/neck location are predictors of better outcomes, whereas previous treatment history is a predictor of poorer outcomes.

Predicting child development and school readiness, at age 5, for Aboriginal and non-Aboriginal children in Australia's Northern Territory.

Positive early development is critical in shaping children's lifelong health and wellbeing. Identifying children at risk of poor development is important in targeting early interventions to children and families most in need of support. We aimed to develop a predictive model that could inform early support for vulnerable children. We analysed linked administrative records for a birth cohort of 2,380 Northern Territory children (including 1,222 Aboriginal children) who were in their first year of school in 2015 and had a completed record from the Australian Early Development Census (AEDC). The AEDC measures early child development (school readiness) across five domains of development. We fitted prediction models, for AEDC weighted summary scores, using a Partial Least Square Structural Equation Model (PLS-SEM) considering four groups of factors-pre-pregnancy, pregnancy, known at birth, and child-related factors. We first assessed the models' internal validity and then the out-of-sample predictive power (external validity) using the PLSpredict procedure. We identified separate predictive models, with a good fit, for Aboriginal and non-Aboriginal children. For Aboriginal children, a significant pre-pregnancy predictor of better outcomes was higher socioeconomic status (direct, β = 0.22 and indirect, β = 0.16). Pregnancy factors (gestational diabetes and maternal smoking (indirect, β = -0.09) and child-related factors (English as a second language and not attending preschool (direct, β = -0.28) predicted poorer outcomes. Further, pregnancy and child-related factors partially mediated the effects of pre-pregnancy factors; and child-related factors fully mediated the effects of pregnancy factors on AEDC weighted scores. For non-Aboriginal children, pre-pregnancy factors (increasing maternal age, socioeconomic status, parity, and occupation of the primary carer) directly predicted better outcomes (β = 0.29). A technical observation was that variance in AEDC weighted scores was not equally captured across all five AEDC domains; for Aboriginal children results were based on only three domains (emotional maturity; social competence, and language and cognitive skills (school-based)) and for non-Aboriginal children, on a single domain (language and cognitive skills (school-based)). The models give insight into the interplay of multiple factors at different stages of a child's development and inform service and policy responses. Recruiting children and their families for early support programs should consider both the direct effects of the predictors and their interactions. The content and application of the AEDC measurement need to be strengthened to ensure all domains of a child's development are captured equally.

Acute intracranial stenting in acute ischemic stroke with underlying atherosclerosis: A two-center retrospective study

Objective In patients with large vessel occlusion, successful reperfusion is a predictor of favorable outcome. However, patients with underlying intracranial atherosclerotic disease (ICAD) show higher rates of immediate reocclusion, frequently requiring rescue stenting. We aimed to investigate the safety, efficacy, and outcome of acute stenting in acute stroke patients with underlying ICAD. Methods Prospective databases from two centers between 2012 and 2021 were reviewed. Adult patients who underwent ICAD-related acute intracranial stenting, after mechanical thrombectomy (MT) were included. Clinical and procedural data, technical success measured by Modified Thrombolysis in Cerebral Infarction score, periprocedural complications, stent restenosis, and follow up mRS at three months were evaluated. Results During a 10-year period, a total of 96 patients with acute stroke and intracranial atherosclerotic steno-occlusive lesions underwent stenting after MT. Mean age was 63 (SD 14) and 54 patients were male (56.3%). Successful reperfusion (TICI ≥ 2b) was achieved in 86 patients (89.6%) following rescue stenting; favorable clinical outcome (mRS &lt; 3) was observed in 32 patients (37.6%). Symptomatic intracranial hemorrhage and mortality were observed in 9.5% and 22.4% of patients, respectively. Multivariate regression yielded older age (OR: 0.477, 95% CI: 0.933–0.999, p=0.046) as an independent negative predictor of favorable functional outcome after acute intracranial stenting. Conclusion Our results suggest that acute intracranial stenting is safe and effective as a rescue treatment after MT in acute stroke patients with underlying ICAD. Younger age was found as an independent predictor of good outcome. Nevertheless, ICAD still carries a high mortality and poor functional clinical outcome.

Long-Term Neurocognitive Outcomes in Pediatric Nonfatal Drowning: Results of a Family Caregiver Survey

BackgroundDrowning is a leading cause of brain injury in children. Long-term outcome data for drowning survivors are sparse. This study reports neurocognitive outcomes for 154 children hospitalized following drowning. MethodsA survey for parent caregivers was distributed online. Likert scale items assessed 10 outcome variables in four domains: motor (three), perception (three), language (three), and social/emotional (one). Cluster analysis, outcome relative risk, and descriptive statistics were applied. ResultsOf 208 surveys received, 154 met inclusion criteria. Coma was the most common admission status (n = 137). Cluster analysis identified three outcome groups: Mild (n = 39), Moderate (n = 75), and Severe (n = 40). Motor impairment with cognitive and perceptual sparing (deefferentation) was present in Moderate (P < 1 × 10−26) and Severe (P < 1 × 10−12) but absent in Mild. Locked-in state was endorsed in both Moderate (83%) and Severe (70%). The strongest predictor of good outcome (Mild) was hospitalization with no medical intervention (relative risk [RR] = 6.7). Responsivity on admission (RR = 4.2) or discharge (RR = 12.22) also predicted good outcome. In-hospital prognostication and counseling predicted outcome weakly (RR = 1.3) or not at all. ConclusionsLong-term outcomes in pediatric drowning ranged widely. Overall, motor impairments exceeded perceptual or cognitive (P < 1 × 10−18), with “locked-in state” endorsed in most (93 of 154). The strongest predictors of good outcome were the lack of necessity for interventions and responsivity on admission or discharge. The eponym “Conrad syndrome” is proposed for locked-in state following nonfatal drowning in children.

Treatment of Pineal Region Lesions in Children.

Pineal region lesions are more common in children than adults; however, therapeutic strategies for pineal region lesions in children are controversial. A retrospective study involving 54 pediatric with pineal region lesions was conducted. The therapeutic strategies for lesions and hydrocephalus were classified and analyzed. Radiotherapy of pineal region lesions was shown to result in better postoperative recovery and fewer complications in the short-term compared with lesion resection. Total resection was related to smaller lesion size, endoscopic procedures, and a better prognosis. Cerebrospinal fluid (CSF) diversion before the resection reduced hydrocephalus recurrences, whereas further lesion resection had a negative short-term influence on CSF diversion. Among the 4 therapeutic strategies to manage hydrocephalus, a third ventriculostomy (ETV) was reasonable and further resection did not have a negative impact on the ETV. The relief of hydrocephalus was also related to better postoperative recovery, a higher total resection rate, fewer complications, and a better prognosis. Logistical regression analysis indicated that lesion size and intracranial complications were predictors of outcome. For lesion treatment, total resection and radiotherapy are essential components in children. Total resection and CSF diversion before resection were beneficial, whereas further lesion resection had a negative impact on CSF diversion. For hydrocephalus treatment, ETV was shown to be the best therapeutic strategy for management of pediatric hydrocephalus. Total resection and better preoperative health status were associated with greater hydrocephalus relief. For the overall prognosis, a lack of hydrocephalus relief was associated with poor outcomes. Lesion size and intracranial complications may be the best predictors of outcome.

Reactivity of complex communities can be more important than stability

Understanding stability—whether a community will eventually return to its original state after a perturbation—is a major focus in the study of various complex systems, particularly complex ecosystems. Here, we challenge this focus, showing that short-term dynamics can be a better predictor of outcomes for complex ecosystems. Using random matrix theory, we study how complex ecosystems behave immediately after small perturbations. Our analyses show that many communities are expected to be ‘reactive’, whereby some perturbations will be amplified initially and generate a response that is directly opposite to that predicted by typical stability measures. In particular, we find reactivity is prevalent for complex communities of mixed interactions and for structured communities, which are both expected to be common in nature. Finally, we show that reactivity can be a better predictor of extinction risk than stability, particularly when communities face frequent perturbations, as is increasingly common. Our results suggest that, alongside stability, reactivity is a fundamental measure for assessing ecosystem health.

Discordance between Next Generation Sequencing and BCR-ABL PCR Measurable Residual Disease in Adult Patients with Ph+ Acute Lymphoblastic Leukemia

Background: It remains unclear whether measurable residual disease (MRD) detected by next-generation sequencing (NGS) or BCR-ABL RT-PCR is more accurate in predicting relapse and guiding clinical management in patients with Ph+ acute lymphoblastic leukemia (ALL). In this multi-center retrospective study, we examine the discordance between BCR-ABL PCR and NGS MRD to better characterize practice patterns for disease monitoring for patients with Ph+ ALL. Methods: We included Ph+ ALL patients from five academic hospitals in the United States who were monitored with both BCR-ABL PCR and NGS-based clonoSEQ (Adaptive Biotechnologies) between 2015 and 2023. Patients were included if they had both baseline BCR-ABL PCR and NGS MRD assessments and at least 1 follow-up MRD assessment using both modalities. BCR-ABL PCR and NGS MRD results were only included if they were taken less than 1 month apart. Patient demographics, BCR-ABL isoform (p190 or p210), and IKZF1, CDK2NA, and PAX5 copy number alterations were also collected. We used frequency counts, median, and interquartile range (IQR) to describe our data. Univariable logistic regression was performed to quantify associations between diagnostic patient features and any post-diagnosis MRD discrepancy (i.e., MRD positive vs. MRD negative) between the two modalities. Results: 93 patients had both BCR-ABL PCR (p190 n=61 [66%], p210 n=21 [23%], both n=8 [9%]) and NGS MRD assessments. Descriptive statistics are shown in Table 1. Figure 1 is a Sankey diagram illustrating the trajectory of BCR-ABL PCR and NGS concordance at 3, 6, and 12 months following diagnosis. 60 patients (64%) had a discrepancy between qPCR and NGS at any time after Ph+ ALL diagnosis while 24 patients (26%) had a discrepancy within the first 3 months. For the 54 patients (58%) receiving transplant, 38 (70.4%) had a post-diagnosis MRD discrepancy. Among all patients, median time from diagnosis to first discrepancy was 3.9 (IQR, 2.3-7.3) months. The most common discrepancy was BCR-ABL PCR detectable / NGS undetectable (n=39, 42% of included patients). In 12 patients (20% of patients with an MRD discrepancy at any time), clinical decision making was changed due to this observed discrepancy in MRD status. While a persistently positive PCR result with negative NGS led to a change in treatment regimen for 8 of these patients (75%), one patient's positive PCR with negative NGS led to the decision to continue current therapy. Further, a positive NGS with negative PCR led to change of treatment in 3 patients. BCR-ABL isoform and copy number variation of target genes were not associated with increased risk of MRD discrepancy, although sample size was limited for the genetic alterations (Table 1). Conclusion: We found a considerable degree of discordance between BCR-ABL PCR and NGS in Ph+ ALL patients. The most common discrepancy was PCR detectable / NGS undetectable, and in case of discordance, PCR positive results are most frequently given precedence in guiding clinical management. In the discordant patients, the presence of MRD positivity via either test drove changes to treatment rather than MRD negativity in one of the two tests. Future studies should investigate whether BCR-ABL PCR or NGS is a better predictor of outcome in Ph+ ALL.

Impact of “Cell-of-Origin” on Outcome after Axicabtagene-Ciloleucel CAR-T Cell Therapy in Relapsed/Refractory Aggressive Non-Hodgkin B-Cell Lymphomas

Introduction: Despite significant advances in characterizing aggressive B-cell non-Hodgkin lymphomas (aNHL) based on molecular and genetic signatures, the Hans algorithm, determined by immunohistochemistry, remains the most commonly used approach to differentiate aNHLs based on the cell-of-origin (COO) into germinal center B-cell (GCB) and non-GCB types. Although the Hans algorithm has demonstrated reliability as a predictor of better outcomes in newly diagnosed GCB cases, conflicting evidence has emerged, particularly in the relapsed/refractory (R/R) setting, and there are no definitive data about the impact of COO in patients (pts) receiving CAR-T cells. Thus, we conducted a retrospective analysis to evaluate the impact of COO extended to R/R aNHLs who underwent treatment with axicabtagene-ciloleucel (axi-cel). Methods: We retrospectively collected data from pts with R/R aNHLs treated with axi-cel at Fred Hutchinson Cancer Center between February 2018 and August 2022. The Hans algorithm, using CD10, BCL6 and MUM1 markers, was employed to stratify the pts into two cohorts: GCB and non-GCB. Paired biopsies of diagnosis and relapse before CAR-T eligibility were reviewed at our institution. Response to CAR-T was assessed at one month per Lugano PET/CT criteria. Univariate cox proportional hazard regression was used to estimate associations between baseline factors and outcomes. Statistically significant factors ( p&amp;lt;.05) in univariate analysis were further evaluated by multivariate analysis. Continuous variables were compared by Mann-Whitney U test and categorical variables by Fischer's exact test. Progression-free survival (PFS) was calculated from the date of CAR-T cell infusion to the date of death from any cause, disease progression or relapse. Overall survival (OS) was calculated from the date of CAR-T cell infusion to the date of death from any cause. Results: Sixty-four pts were included in this analysis, with an equal distribution of pts in the two cohorts: 32 with GCB subtype and 32 with non-GCB subtype. Baseline pts' characteristics and histology subtypes are listed in Table 1. Transformed follicular lymphoma and primary mediastinal B-cell lymphoma were not included in this analysis. The presence of bulky disease (defined as &amp;gt;5cm diameter) was higher in the GCB subtype (56% vs 22%, p&amp;lt;.001). Although primary refractory cases were more frequent in the GCB cohort (87.5 vs 66%), statistical significance was not reached (NR)( p=.07). The same proportion of pts received bridging therapy in the two groups (53% vs 53%, p=.99). Pts evaluable for response assessment were 62. Median time to best response was 29 days (range, 21-186) for GCB pts and 31 days (range, 22-182) for non-GCB pts ( p=.91). The overall response rate was 70% for GCBs (34.5% complete response [CR], 34.5% partial response [PR]) and 75% for non-GCBs (44% CR, 31% PR). After a median follow-up of 24.5 months (range, 9-121), comparable outcomes were observed for both the COO groups: despite the estimated median OS of 14 months (95% CI, 4.73-NR) for GCB vs 40 months (95% CI, 12.55-67.46) for non-GCB, we did not find any significant differences ( p=.73) (Figure 1A). Estimated median PFS was 10 months (95% confidence interval [CI], 3.5-16) for GCB and 11 months (95% CI, 0-24) for non-GCB ( p=.57) (Figure 1B). The 2-year OS and PFS were: GCB, 45% (95% CI, 30-69) and 44% (95% CI, 29-67) respectively; non-GCB, 55% (95% CI, 38-79) and 29% (95% CI, 16-55), respectively. Treatment-related toxicities did not differ between GCB and non-GCB, with cytokine-release syndrome rates of 97% vs 94% ( p=.99) and neurotoxicity rates of 53% vs 62.5% ( p=.61), respectively. The incidence of infectious complications was 25% vs 19% ( p=.76). On univariate analysis, the impact of COO on OS (HR=0.82, 95% CI 0.39-1.73, p=.60) and PFS (HR=1.18, 95% CI 0.61-2.28, p=.62) was undetermined. After adjusting for bulky disease, elevated LDH, absolute lymphocyte count≤1000/uL, performance status≥2, &amp;gt;2 lines of therapy and response status before axi-cel infusion, the impact of COO on OS (adjusted HR [aHR]=1.73, 95% CI 0.71-4.22, p=.23) and PFS (aHR=2.01, 95% CI 0.93-4.35, p=.08), remained undetermined. Conclusion: We could not confirm an association between COO, as determined by Hans algorithm, and outcomes in R/R aNHLs who received axi-cel at our center. Prospective analyses on larger datasets and other types of CAR-T products are needed.

Ejection fraction, B-lines, and global longitudinal strain evaluated with rest transthoracic echocardiography to assess prognosis in patients with chronic coronary syndromes

Aim: Transthoracic echocardiography (TTE) is the first-line imaging test for patients with chronic coronary syndrome (CCS) and the cornerstone of risk stratification is left ventricular (LV) ejection fraction (EF). Aim of the study was to investigate the value of TTE supplemented with strain echocardiography (STE) and lung ultrasound (LUS) to assess the risk of patients with CCS. Methods: In a prospective, single-center, observational study, from November 2020 to December 2022, 529 consecutive patients with CCS were recruited. All patients were evaluated at rest. A single vendor machine (GE Vivid E95) was used. EF with biplane Simpson’s method (abnormal cut-off &lt; 50%), LV global longitudinal strain (GLS%, abnormal cut-off ≤ 16.2% by receiver-operating characteristics analysis) by STE, and B-line score (abnormal cut-off ≥ 2) by LUS (4-site simplified scan) were assessed. Integrated TTE score ranged from 0 (all 3 parameters normal) to 3 (all parameters abnormal). All patients were followed-up and a composite endpoint was considered, including all-cause death, acute coronary syndrome (ACS), and myocardial revascularization. Results: During a follow-up of 14.2 months ± 8.3 months, 72 events occurred: 10 deaths, 11 ACSs, and 51 myocardial revascularizations. In multivariable analysis, B lines [hazard ratio (HR) 1.76, 95% confidence Interval (CI) 1.05–2.97; P = 0.03], and GLS ≤ 16.2% (HR 2.0, 95% CI 1.17–3.45; P = 0.01) were independent predictors of events. EF &lt; 50% was a significant predictor in univariate, but not in multivariable analysis. Event rate at 2 years increased from score 0 (8%), to score 1 (21%), 2 (23%), and 3 (40%), P &lt; 0.0001. Conclusions: TTE with left ventricular ejection fraction (LVEF) can be usefully integrated with STE for GLS, and LUS for B-lines, for better prediction of outcome in CCS. The 3 parameters can be obtained in every echo lab with basic technology, no harm, no risk, and no stress.

Prognostic Value of Venous Outflow Profiles on Multiphase CT Angiography for the Patients with Acute Ischemic Stroke After Endovascular Thrombectomy.

To evaluate the prognostic value of venous outflow (VO) profiles evaluated on multiphase CTA (mCTA) for the patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). We retrospectively collected 150 patients with AIS who underwent pre-treatment CT perfusion (CTP) evaluation and subsequent EVT from April 2018 to April 2022. Three-phases (peak arterial phase, peak venous phase, late venous phase) CTA was reconstructed from CTP raw data, and VO was evaluated on three-phases CTA, respectively. Favorable VO was regarded as a cortical vein opacification score of 3-6, and unfavorable VO as a score of 0-2. Good outcome was defined as modified Rankin Scale score of 0-2 at 90 days after EVT. Multivariate logistic regression analysis was performed to explore the predictors of good outcome. Prognostic value was assessed and compared using receiver operating characteristic (ROC) curves and Delong test. We found that good outcome was achieved in 85 (56.7%) patients. Among the mCTA-derived VO profiles, only favorable peak venous phase VO was found to be independently associated with good outcome (P < 0.001). After integrating favorable peak venous phase VO with lower post-treatment National Institute of Health Stroke Scale score at 24 hours, successful recanalization and favorable hypoperfusion intensity ratio, the predictive ability for a good outcome was significantly improved than before (area under the ROC curve; 0.947 vs 0.881; P = 0.002). This study supports that favorable peak venous VO profiles on mCTA might be a promising biomarker in predicting the good outcome in patients with AIS after EVT.

Outcomes Based on Angiographic vs Functional Significance of Complex 3-Vessel Coronary Disease: FAME 3 Trial

BackgroundThe functional SYNTAX score (FSS), which incorporates functional information as assessed by fractional flow reserve (FFR), is a better predictor of outcome after percutaneous coronary intervention (PCI) in patients with less complex coronary artery disease (CAD). ObjectivesThis study sought to test the prognostic value of the FSS in patients with complex CAD eligible for coronary artery bypass grafting (CABG). MethodsThe FAME 3 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3) trial compared FFR-guided PCI with CABG in patients with angiographic 3-vessel CAD. In this prespecified substudy, the angiographic core laboratory calculated the SYNTAX score (SS) and then the FSS by eliminating lesions that were not significant based on FFR. Outcomes in the PCI patients based on the FSS and the SS were compared to each other and to the patients treated with CABG. ResultsThe FSS reclassified more than one-quarter of patients from an SS >22 to an FSS ≤22. In the 50% of PCI patients who had an FSS ≤22, the primary endpoint occurred at a similar rate to patients treated with CABG (P = 0.77). The primary endpoint in patients without functionally significant 3-vessel CAD was similar to the CABG group (P = 0.97). The rate of myocardial infarction and revascularization among all deferred lesions was 0.5% and 3.2%, respectively. ConclusionsBy measuring the FSS, one can identify 50% of patients who have a similar outcome at 1 year with PCI compared with CABG. Lesions deferred from PCI based on FFR have a low event rate.