Molecular classification improves risk assessment in adult BCR-ABL1-negative B-ALL.

Genomic classification has improved risk assignment of pediatric, but not adult B-lineage acute lymphoblastic leukemia (B-ALL). The international UKALLXII/ECOG-ACRIN E2993 (#NCT00002514) trial accrued 1229 adolescent/adult patients with BCR-ABL1- B-ALL (aged 14 to 65 years). Although 93% of patients achieved remission, 41% relapsed at a median of 13 months (range, 28 days to 12 years). Five-year overall survival (OS) was 42% (95% confidence interval, 39, 44). Transcriptome sequencing, gene expression profiling, cytogenetics, and fusion polymerase chain reaction enabled genomic subtyping of 282 patient samples, of which 264 were eligible for trial, accounting for 64.5% of E2993 patients. Among patients with outcome data, 29.5% with favorable outcomes (5-year OS 65% to 80%) were deemed standard risk (DUX4-rearranged [9.2%], ETV6-RUNX1/-like [2.3%], TCF3-PBX1 [6.9%], PAX5 P80R [4.1%], high-hyperdiploid [6.9%]); 50.2% had high-risk genotypes with 5-year OS of 0% to 27% (Ph-like [21.2%], KMT2A-AFF1 [12%], low-hypodiploid/near-haploid [14.3%], BCL2/MYC-rearranged [2.8%]); 20.3% had intermediate-risk genotypes with 5-year OS of 33% to 45% (PAX5alt [12.4%], ZNF384/-like [5.1%], MEF2D-rearranged [2.8%]). IKZF1 alterations occurred in 86% of Ph-like, and TP53 mutations in patients who were low-hypodiploid (54%) and BCL2/MYC-rearranged (33%) but were not independently associated with outcome. Of patients considered high risk based on presenting age and white blood cell count, 40% harbored subtype-defining genetic alterations associated with standard- or intermediate-risk outcomes. We identified distinct immunophenotypic features for DUX4-rearranged, PAX5 P80R, ZNF384-R/-like, and Ph-like genotypes. These data in a large adult B-ALL cohort treated with a non-risk-adapted approach on a single trial show the prognostic importance of genomic analyses, which may translate into future therapeutic benefits.

We need to do better: Readability analysis of online patient information on cancer survivorship and fertility preservation.

OBJECTIVE: National Institute of Health recommends that patient education material should be written at no greater than 6th-grade level. Cancer survivorship and fertility preservation discussion with patients is recommended by many national societies and being done more frequently. We sought to analyze online patient information on cancer survivorship and fertility preservation to see if they meet the criteria set by national guidelines. METHODS: Online patient information on cancer survivorship and fertility preservation was collected and analyzed by six of the most common readability tests. Only websites in English and free to access were used. RESULTS: A total of 15 separate websites for cancer survivorship and fertility preservation was used. All websites failed to meet national guidelines. Cancer survivorship information was written at a high school senior and a 12th-grade level. Fertility preservation information was written at a high school-senior and junior college level. CONCLUSION: Online patient information on cancer survivorship and fertility preservation did not meet national guidelines. Testing across six of the most used readability indexes showed that information is challenging to understand for the general patient population. POLICY STATEMENT: This article shares an insight into the complex and growing fields of cancer survivorship and fertility preservation. Educating patients about their condition is critical and improves outcomes and participation in shared decision making. Healthcare policy should focus on implementing a system that will provide culturally and linguistically appropriate information in the community for patients about their disease.

Undifferentiated Shock and Extreme Elevation of Procalcitonin Related to Kratom Use.

An 18-year-old male with history of polysubstance abuse presented to the emergency department with intractable vomiting, diarrhea, and abdominal pain for one day after the consumption of kratom. Examination revealed arterial hypotension, tachycardia, and prolonged capillary refill. Laboratory studies showed white blood cell count (WBC) of 23.6 × 109/L, serum creatinine 4.0 mg/dL, lactate 6 mmol/L, and procalcitonin >200 ng/mL. Urine and blood drug screen were unremarkable. Radiology and echocardiogram were noncontributory. He received fluid resuscitation and broad spectrum antibiotics. Vasopressors were subsequently added to manage persistent shock. He remained afebrile, and his blood cultures were negative. His shock and associated organ dysfunctions improved over the next 72 hours. On discharge, his procalcitonin level decreased to 9.55 ng/mL, leukocytosis resolved, and the creatinine returned to baseline. This case describes an extremely rare presentation related to kratom, an herb marketed as an opioid alternative, with significant potential for addiction and withdrawal syndrome. How to cite this article: Zuberi M, Guru PK, Bansal V, Diaz-Gomez J, Grieninger B, Alejos D. Undifferentiated Shock and Extreme Elevation of Procalcitonin Related to Kratom Use. Indian J Crit Care Med 2019;23(5):239-241.

Adult Presentation of Ornithine Transcarbamylase Deficiency: 2 Illustrative Cases of Phenotypic Variability and Literature Review.

Ornithine transcarbamylase (OTC) deficiency is an X-linked recessive disorder that usually presents in the neonatal period. Late-onset presentation of OTC can cause mild to severe symptoms. We describe laboratory and clinical findings of late-onset presentations of OTC deficiency. We conducted a literature search using search terms "ornithine transcarbamylase deficiency," "late onset presentation," and "hyperammonemia" from January 1, 1987, to December 31, 2016, was performed. Only papers published in English were included. We searched on PubMed, MEDLINE, and Google Scholar. We also present 2 OTC deficiency cases. A total of 30 adult cases had late-onset presentation of OTC deficiency reported. The majority were women (57%) with a median age of 37 years. The median level of ammonia was 308 mmol/L and the mortality rate was 30%. Our case 1 was a 40-year-old woman who succumbed to neurologic complications after a hyperammonemia crisis following an increased protein intake. Our case 2 was a 43-year-old woman with seizures associated with increased ammonia levels. Our 2 case reports show the wide phenotypic variability and severity in late-onset presentation of OTC ranging from seizures to cerebral herniation. Our literature review is the first to detail published laboratory and neurologic sequelae of late-onset OTC deficiency.

Evaluation of Hospital-wide Readmission Risk Calculator to Predict 30-Day Readmission in Neurocritical Care Patients.

BACKGROUND AND PURPOSE: Thirty-day hospital readmissions have been shown to be a measure of quality and result in higher mortality and increased costs. Readmissions are a target for hospitals and payers; thus, several centers have developed predictive readmission scores to identify high-risk patients. The purpose of this study was to evaluate the current hospital-wide readmission risk calculator and the ability of this tool to predict 30-day readmissions in the neurocritical care population. METHODS: A retrospective chart review was performed that included 340 consecutive patients admitted to our neuroscience critical care unit. Data including readmission scores, reason for admission, length of stay, and whether they were readmitted were recorded. RESULTS: After removing patients without readmission scores or who died at the end of the original admission, the records of N = 279 patients were analyzed. Patients were more likely to be readmitted if they were initially emergently hospitalized or if there was a history of malignancy. Readmitted patients had a longer original hospital length of stay. Furthermore, 65.8% of the patients who were given a "low risk" for readmission were readmitted within 30 days. CONCLUSIONS: This small set of data in a specific patient population found that the current risk prediction score was inaccurate in predicting readmission in the neuroscience intensive care unit population. Further evaluation is needed of a larger patient population to generalize these results for all neuroscience intensive care unit patients. To design an accurate readmission risk tool, centers should create unique readmission scores based on less heterogeneous patient populations.

Sleep Apnea in Patients Hospitalized With Acute Ischemic Stroke: Underrecognition and Associated Clinical Outcomes.

STUDY OBJECTIVES: To evaluate clinical recognition of sleep apnea and related outcomes in patients hospitalized with acute ischemic stroke. METHODS: A retrospective study of all patients hospitalized with acute ischemic stroke from April 2008 to December 2014. The primary predictor and outcome variables were sleep apnea and hospital mortality, respectively. Secondary outcomes were mechanical ventilation, hospital length of stay, and the survivor's functional level by the modified Rankin scale. A sensitivity multivariate regression analysis included the propensity score for cardiovascular comorbidities and sleep apnea. RESULTS: Of 989 patients, 190 (19%) were considered to have sleep apnea. Only 42 patients (22%) received any treatment for sleep apnea during the hospital stay. Despite higher prevalence of cardiovascular comorbidities, the patients with sleep apnea had lower hospital mortality, 1% versus 5.6% in patients without sleep apnea (odds ratio [OR] 0.18; 95% confidence interval [CI], 0.03-0.58, P = .002). Only the National Institutes of Health Stroke Scale (NIHSS) and the Glasgow coma scale (GCS) were significant predictors of adjusted hospital mortality (OR 1.06, 95% CI 1.01-1.11, P = .01 and OR 0.61, 95% CI 0.51-0.69, P ≤ .001, respectively). A composite clinical propensity score for sleep apnea and cardiovascular comorbidities was significantly associated with decreased mortality, independent to either NIHSS (OR 0.11, 95% CI 0.017-0.71; P = .02) or GCS (OR 0.07, 95% CI 0.01-0.52; P = .01). CONCLUSIONS: Prevalence of sleep apnea in our study was low, likely because of clinical underrecognition. Despite having more cardiovascular disease, the patients with acute stroke and sleep apnea had less severe neurological injury and lower unadjusted mortality than those without a history of sleep apnea.

A Preliminary Observational Study of Anovulatory Uterine Bleeding After Aneurysmal Subarachnoid Hemorrhage.

INTRODUCTION: It was observed that women with aneurysmal subarachnoid hemorrhage (aSAH) tended to have earlier menses than a typical 21- to 28-day cycle. The goal was to determine whether there is an association between aSAH and early onset of menses. METHODS: All cases of aSAH in women aged 18 to 55 years who were admitted to our facility's neuroscience intensive care unit from June 1, 2011, to June 30, 2012, were reviewed. The electronic healthcare record for each of these patients was examined for documentation of menses onset, computed tomography of the head, brain aneurysm characteristics, modified Fisher score and Glasgow Coma Scale on admission, presence/absence of vasospasm, medical/surgical history, and use of medications that affect the menstrual cycle. The mean onset of menses in this study population was compared with the mean of 21 to 28 days with the 1-sample t test. RESULTS: During the study period, 103 patients with subarachnoid hemorrhage were admitted. Sixty-one were women, and 15 were aged 18 to 55 years. Nine of the 15 (60%) had documentation of menses occurring during their initial week of hospitalization; 1 patient had documentation of menses on hospital day 12. There is a significant difference when the mean onset of menses in our patient population is compared with the approximate normal menstrual cycle of 21 to 28 days (P < .01). CONCLUSION: Early onset of menses or abnormal uterine bleeding after SAH may occur in women with aSAH and typically within the first 7 to 10 days after intracranial aneurysm rupture. The physiologic cause of early onset of menses after aSAH, whether primary or secondary, remains unknown.

Neurological outcomes of patients with history of obstructive sleep apnea after a cardiac arrest.

BACKGROUND: Cardiac arrest survivors may have disabilities due to hypoxic brain injury. Patients with obstructive sleep apnea are exposed to intermittent hypoxemia that may lead to ischemic preconditioning. We have hypothesized that patients with obstructive sleep apnea have better neurological outcomes following a cardiac arrest due to preconditioning of the brain. METHODS: We retrospectively analyzed all the survivors of in-hospital cardiac arrest from January 2006 to September 2016. Patients with confirmed or suspected obstructive sleep apnea were selected for further analysis and those without were used as comparison. Primary outcome was neurological functionality on hospital discharge by the Cerebral Performance Category. RESULTS: A total of 739 patients had cardiac arrest within the study period. The immediate mortality rate was 59% (N=43) in patients with obstructive sleep apnea and 94% (N=623) in those without (p<0.001). Approximately 10% (N=73) were discharged alive and these were selected for further analysis. Patients without obstructive sleep apnea had more frequently "Poor" outcomes compared to those with obstructive sleep apnea (OR 2.91; 95% CI, 1.11-7.66; p=0.03). After adjusting in a multivariate analysis, obstructive sleep apnea was "protective" of "Poor" neurological outcomes: adjusted OR 0.21; 95% CI, 0.06-0.64; p=0.01. CONCLUSION: Patients with obstructive sleep apnea had better unadjusted survival rates, and favorable adjusted neurological outcomes at discharge compared to those without obstructive sleep apnea. These results suggest that obstructive sleep apnea patients may tolerate better acute brain ischemia due to preconditioning.

Update on Neurocritical Care of Stroke.

PURPOSE OF REVIEW: This review will highlight the recent advancements in acute ischemic stroke diagnosis and treatment, with special attention to new features and recommendations of stroke care in the neurocritical care unit. RECENT FINDINGS: New studies suggest that pre-hospital treatment of stroke with mobile stroke units and telestroke technology may lead to earlier stroke therapy with intravenous tissue plasminogen activator (tPA), and recent studies show tPA can be given in previously contraindicated situations. More rapid automated CT perfusion and angiography may demonstrate a vascular penumbra for neuroendovascular intervention. Further, the greatest advance in acute stroke treatment since 2014 is the demonstration that neuroendovascular catheter-based thrombectomy with stent retrievers recanalizing intracranial large vessel occlusion (LVO) improves both recanalization and long-term outcomes in several trials. Hemorrhagic transformation and severe large infarct cerebral edema remain serious post-stroke challenges, with new guidelines describing who and when patients should get medical or surgical intervention. The adage "time is brain" directs the most evidence-based approach for rapid stroke diagnosis for tPA eligible and LVO recanalization using an orchestrated team approach. The neurocritical care unit is the appropriate location to optimize stroke outcomes for the most severely affected stroke patients.

Cerebral Venous Thrombosis Associated with Intracranial Hemorrhage and Timing of Anticoagulation after Hemicraniectomy.

BACKGROUND: Cerebral venous thrombosis (CVT) is a rare cerebrovascular event that can present with headache, seizure, and focal neurological deficits. Approximately 30%-40% of patients with CVT also present with intracranial hemorrhage. Current guidelines recommend anticoagulation after CVT even in the setting of intracranial hemorrhage, but the timing of initiation is unclear. We present a case of CVT where timing of anticoagulation was unclear by current guidelines. METHODS: We conducted a literature search with search terms of "cerebral venous thrombosis," "intracranial hemorrhage," and "anticoagulation." Abstracted information included anticoagulation status and time of initiation of anticoagulation. We present a 30-year-old woman with sudden onset of right hemiplegia, global aphasia, and new-onset seizures diagnosed with left transverse and sigmoid sinus thrombosis with intraparenchymal hemorrhage. The patient was treated with endovascular thrombectomy and decompressive hemicraniectomy due to hemorrhage expansion, and anticoagulation was restarted 8 days after hemicraniectomy. RESULTS: The literature review demonstrated a wide variation of timing for anticoagulation initiation in patients with CVT and intracranial hemorrhage. Most started anticoagulation within 24 hours of admission with similar functional neurological recovery. Current guidelines on the treatment of CVT, even with intracranial hemorrhage, recommend anticoagulation. Most reports in the literature state initiation of anticoagulation within 24 hours. However, the literature does not definitively state when to initiate anticoagulation in a patient with CVT, intracranial hemorrhage, thrombectomy, and decompressive hemicraniectomy. CONCLUSION: This case illustrates the challenge of determining when to resume anticoagulation for CVT.