Prediction of early (4-week) mortality in acute myeloid leukemia with intensive chemotherapy

The progress with intensive chemotherapy and supportive care measures has improved survival in patients with newly diagnosed acute myeloid leukemia (AML). Given the recent development of effective low intensity therapies, an optimal decision on the therapy intensity may improve survival through the avoidance of early mortality. We reviewed the outcome of 3728 patients with newly diagnosed AML who received intensive chemotherapy between August 1980 and May 2020. Intensive chemotherapy was defined as a cumulative cytarabine dose ≥ 700 mg/m² during induction therapy. We divided the whole cohort into a training and validation group at a 3:1 ratio. The population was divided into a training (2790 patients) and a validation cohort (938 patients). The median age was 55 years (range, 15-99). Among them, 442 patients (12%) had core-binding factor AML. Binary logistic regression identified older age, worse performance status, hyperbilirubinemia, elevated creatinine, hyperuricemia, cytogenetic abnormalities other than CBF and -Y, and pneumonia as adverse prognostic factors for an early 4-week mortality. This risk classification for early mortality was verified in the validation cohort of patients. In the validation cohort of more recently treated patients from 2000 to 2017, the 4-week mortality rates with intensive chemotherapy were 2%, 14%, and 50% in the low-, high-, and very high-risk group, respectively. The mortality rates with low intensity therapies were 3%, 9%, and 20%, respectively. The risk classification guides treatment intensity by the assessment of age, frailty, organ dysfunction, cytogenetic abnormality, and infection to avoid early mortality.     

Stakeholder-Generated Implementation Strategies to Promote Evidence-Based ADHD Treatment in Community Mental Health

Community implementation of evidence-based practices (EBPs) for Attention Deficit/Hyperactivity Disorder (ADHD) is greatly lacking. A recent randomized community-based trial of an EBP for ADHD (Supporting Teens’ Autonomy Daily; STAND) demonstrated suboptimal implementation and effectiveness outcomes. In the present study, we conducted an Innovation Tournament (IT) with agency staff stakeholders (N?=?26) to identify barriers to successful implementation of STAND and implementation strategies for a revised service delivery model. We conducted member-checking of agency staff-generated ideas with parents (N?=?226) and subsequent querying of additional parent (N?=?226) and youth-generated (N?=?205) strategies to improve care. Go-Zone plots were utilized to identify strategies with the highest feasibility and importance. Practical barriers (i.e., transportation, scheduling difficulties) and parent/youth engagement were the most commonly cited obstacles to successful implementation of STAND in community contexts. Eighteen “winning” implementation strategies were identified that survived member checking. These were classified as train and educate stakeholders (n?=?5; e.g., train agency supervisors to deliver supervision, digitize treatment materials and trainings), engage consumers (n?=?9; e.g., begin treatment with rapport building sessions, increase psychoeducation), provide interactive assistance (n?=?2; e.g., add group supervision, increase roleplay in supervision), and use of evaluative/iterative strategies (n?=?2; e.g., perform fidelity checks, supervisor review of session recordings). Parents and youth desired longer duration of treatment and increased focus on maintenance. Strategies will be developed and tested as part of a pilot effectiveness trial designed to refine STAND’s service delivery model.

Trial Registration NCT02694939 www.clinicaltrials.gov

     

Criteria for Emergency Brain MRI During Stroke-Alert

ObjectivesIntravenous (IV) tissue plasminogen activator (tPA) should be given to patients with acute ischemic stroke (AIS) and avoided in stroke mimics (SM). Select use of emergency brain magnetic resonance imaging (eMRI-brain) in stroke-alerts aids diagnosis, but accepted utilization criteria for eMRI-brain do not currently exist. We developed criteria for eMRI-brain and report the yield of eMRI-brain in stroke-alert patients.Materials and MethodsWe developed three history-based criteria for performing eMRI-brain during stroke-alerts: (1) history of previous similar deficits, (2) change in consciousness at onset of symptoms, (3) symptom presentation consistent with migraine aura. We then performed a retrospective chart review of patients who presented as a stroke-alert over a 5-year period and determined how these criteria affected administration of IV tPA to AIS and SM patients.ResultsAmong 3,512 stroke-alerts, 230 (8.1%) patients met our criteria for eMRI-brain exams: 217 (92.6%) had SM and 17 (7.4%) had AIS. Our IV tPA decision-making analysis showed that based on eMRI-brain IV tPA was less frequently administered to SM patients (PCC-0.841, p=0.036) with less failures to administer IV tPA to patients with AIS (PCC -0.907, p-value=0.013, Pearson correlation coefficient). No patients became ineligible for IV tPA due to MRI-related time delays.ConclusionsOur history based criteria for performing eMRI-brain during stroke-alerts show a high yield of stroke mimics. Selective eMRI-brain improves decision-making accuracy regarding IV tPA administration.     

Enhanced UV-Induced Skin Carcinogenesis in Transgenic Mice Overexpressing Proprotein Convertases

The proprotein convertases (PCs) furin and PACE4 process numerous substrates involved in tumor growth, invasion, and metastasis. We have previously shown that PCs increase the susceptibility to chemical skin carcinogenesis. Because of the human relevancy of UV radiation in the etiopathogenesis of human skin cancer, we investigated whether or not transgenic mice overexpressing either furin alone or both furin and PACE4 show increased susceptibility to UV carcinogenesis. After backcrossing our previously described furin and PACE4 transgenic lines, targeted to the epidermis, into a SKH-1 background, we exposed both single and double transgenic mice to UV radiation for 34 weeks. The results showed an increase in squamous cell carcinoma (SCC) multiplicity of approximately 70% in the single furin transgenic mouse line SF47 (P < .002) and a 30% increase in the other single transgenic line SF49 when compared to wild-type (WT) SKH-1 mice. Interestingly, there was also an increase in the percentage of high histologic grade SCCs in the transgenic lines compared to the WT mice, i.e., WT = 9%, SF47 = 15%, and SF49 = 26% (P < .02). Targeting both furin and PACE4 to the epidermis in double transgenic mice did not have an additive effect on tumor incidence/multiplicity but did enhance the tumor histopathologic grade, i.e., a significant increase in higher grade SCCs was seen in the bigenic mouse line SPF47 (P < .02). Thus, we observed an increased susceptibility to UV in single furin transgenic mice that was not substantially enhanced in the double furin/PACE4 transgenic mice.     

Combined Multichannel Intraluminal Impedance-pH (MII-pH): Multicenter Report of Normal Values from 117 Children

Pancreatic cancer is the fourth leading cause of cancer deaths in the USA. Although some patients will present with premalignant pancreatic lesions (i.e., intraductal papillary mucinous neoplasms) or localized tumors amenable to curative resection, the majority of patients will unfortunately present with technically unresectable or metastatic disease. This review of the recent medical literature will discuss the optimal work-up and management of premalignant pancreatic lesions and the surgical management of localized, borderline resectable, and locally advanced (i.e., unresectable) pancreatic tumors. It will focus on new criteria used to define surgical “resectability,” the significance and clinical impact of surgical margins, the role of multimodality therapy in the management of patients with borderline resectable or locally advanced tumors, the role of surgery for local or distant recurrence, and minimally invasive surgical approaches.