Search

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. The persistence of mutated NPM1 or FLT3 -ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoetic cell transplant (alloHCT) has been established as associated with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1 , at this treatment landmark however remains incompletely defined. We performed testing for residual IDH1 variants ( IDH1 m) in pre-transplant CR1 blood of 148 adult patients undergoing alloHCT for IDH1 -mutated AML at a CIBMTR site between 2013-2019. No post-transplant differences were observed between those testing IDH1 m positive (n=53, 36%) and negative pre-transplant (overall survival: p = 0.4; relapse: p = 0.5). For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3 -ITD, only detection of persistent mutated NPM1 and/or FLT3 -ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD or increased post-transplant relapse risk., Competing Interests: Conflicts of Interest Statements Hourigan: The National Heart, Lung, and Blood Institute receives research funding for the laboratory of Dr. Hourigan from the Foundation of the NIH AML MRD Biomarkers Consortium. Auletta: Advisory Committee: AscellaHealth and Takeda El Chaer: Consultant: SPD Oncology, Amgen, Association of Community Cancer Centers; Clinical Trial Grant Support (PI) to the University of Virginia: Amgen, BMS, Celgene, SPD Oncology, Sanofi, Bristol Myers Squibb, FibroGen, PharmaEssentia, BioSight, MEI Pharma, Novartis, Arog pharmaceuticals; Travel grant: DAVA Oncology E Chen: Consultant: Rigel Pharmaceuticals and AbbVie Corner: Employment: Bio-Rad Laboratories Jimenez Jimenez: Funding: Abbvie De Lima: Advisory Board: Pfizer, Bristol Myers Squibb; Data Safety Monitoring Board: Novartis, Abbvie; Research Funding: Miltenyi Biotec Kebriaei: Consultant: Pfizer, Jazz Pharmaceuticals

Two patients receiving oral etoposide therapy developed Pneumocystis jirovecii pneumonia during chemotherapy with significant lymphopenia without corticosteroid use. In this commentary we discuss cellular mechanisms by which etoposide induced CD4+ T lymphocyte dysfunction and reduced survival may lead to predisposition to P. jirovecii infection., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Inferior outcomes of Black patients with lung cancer compared with other racial groups are often linked to socioeconomic factors. It is crucial to determine whether a varying prevalence of targetable mutations limits treatments and contributes to disparities., Materials and Methods: We conducted a meta-analysis on the prevalence of lung cancer EGFR , ALK , ROS-1 , and BRAF mutations in Black patients compared with White, Hispanic, and Asian patients. We searched PubMed/MEDLINE, Cochrane Library, EMBASE, CENTRAL, Google Scholar, and clinicaltrials.gov databases. We selected studies reporting the prevalence of at least one mutation in the Black population. We calculated the pooled prevalence of mutations using fixed effects, exact binomial distributions, and Freeman-Turkey double arcsine transformation to stabilize the variances., Results: Twenty studies with 11,867 patients were included. In Black patients, EGFR was the most prevalent mutation (6%; 95% CI, 5 to 7), followed by BRAF (1%; 95% CI, 0 to 2), ALK (1%; 95% CI, 0 to 2), and ROS-1 (0%; 95% CI, 0 to 1). Black patients had a lower prevalence of EGFR mutations than White, Hispanic, and Asian patients ( P < .01). BRAF mutations were less prevalent in Black compared with White patients ( P < .05), and ALK mutations were less prevalent when compared with Hispanic patients ( P < .05)., Conclusion: EGFR is the most frequent mutation found in Black patients, although its prevalence is lower than that in other races. Black patients have a low overall prevalence of ALK , ROS-1 , and BRAF mutations. Given that disproportional eligibility for targeted therapies may be contributing to inferior outcomes, research focused on the Black population is needed to evaluate specific tumor characteristics and therapeutic strategies., Competing Interests: Gilberto LopesHonoraria: Boehringer IngelheimConsulting or Advisory Role: Pfizer, AstraZenecaResearch Funding: Merck Sharp & Dohme, EMD Serono, AstraZeneca, Blueprint Medicines, Tesaro, Bavarian Nordic, Novartis, G1 Therapeutics, Adaptimmune, BMS, GlaxoSmithKline, Abbvie, Rgenix, Pfizer, Roche, Genentech, Lilly, Janssen, LucenceTravel, Accommodations, Expenses: Boehringer Ingelheim, Pfizer, E.R. Squibb Sons, LLC, JanssenNo other potential conflicts of interest were reported.

Opinion Statement: Venous compression syndromes present a diagnostic and therapeutic challenge as the clinical presentation can be vague, diagnostic criteria are often not present, and high quality standardization of when and how to treat is not available in part due to the limited number of cases reported and also due to the limited literature available. Significant venous compression should be considered when clinical symptoms correlate to location of compression and there is evidence of hemodynamic changes including venous hypertension, collateral/variceal formation, and/or thrombus formation. In general, treatment of venous compression should address the etiology of the compression as opposed to just treating symptoms associated with it such as significant varices or anticoagulation for thrombus to avoid recurrence of symptoms.

Purpose: This study was designed to characterize the pharmacokinetic profile and to assess bioequivalence of the sponsor's test formulation (imatinib mesylate 400 mg tablets) with an innovator product (Gleevec 400 mg tablets, Novartis Pharmaceuticals) under fed conditions, in adult patients of Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) stabilized on imatinib mesylate 400 mg. In addition, the aim of this study was to monitor the safety profile of investigational medicinal products (IMPs)., Materials and Methods: A multicenter, randomized, open label, two-period, crossover, single dose bioequivalence study was designed for conduct under fed conditions in 42 adult Ph+ CML patients already stabilized on imatinib 400 mg tablets. Pharmacokinetic parameters Tmax, Cmax, and AUC0-24 were calculated using a non-compartmental model on validated WinNonlin software. Validated SAS software was used for statistical evaluation of data. The safety profile of investigational products was monitored during the course of study by applying a clinical process for recording observed untoward effects postadministration of investigational products., Results: The 90% confidence intervals for the test/reference mean ratios of the ln-transformed PK variables Cmax (99.0%) and AUC0-24 (99.2%) were within an acceptable range of 80%-125%, as per bioequivalence assumptions. Both formulations were well tolerated after oral administration of IMPs., Conclusion: The test product was found to be bioequivalent and safe, and thus can be used interchangeably in clinical practice.

Post-infarction ventricular septal defect (PI-VSD) is a devastating complication that carries a high mortality with or without surgical repair. Percutaneous closure is an attractive alternative in select patients though requires appropriate characterization of the PI-VSD as well as careful device and patient selection. We describe a multidisciplinary and multi-modality imaging approach to successful percutaneous closure of a PI-VSD.

Background: We sought to determine the association between cigarette smoking and carotid plaque ultrasound morphology in a multiethnic cohort., Methods: We analyzed 1,743 stroke-free participants (mean age 65.5 ± 8.9 years; 60% women; 18% white, 63% Hispanic, 19% black; 14% current and 38% former smokers, 48% never smoked) from the Northern Manhattan Study using an ultrasound index of plaque echodensity, the Gray-Scale Median (GSM). Echolucent plaque (low GSM) represents soft plaque and echodense (high GSM) more calcified plaque. The mean GSM weighted by plaque area for each plaque was calculated for those with multiple plaques. Quintiles of GSM were compared to no plaque. Multinomial logistic regression models were used to assess associations of cigarette smoking with GSM, adjusting for demographics and vascular risk factors., Results: Among subjects with carotid plaque (58%), the mean GSM scores for quintiles 1-5 were 48, 72, 90, 105, and 128, respectively. Current smokers had over a two fold increased risk of having GSM in quintile 1 (odds ratio (OR) = 2.17; 95% confidence interval (CI), 1.34-3.52), quintile 2 (OR = 2.33; 95% CI, 1.42-3.83), quintile 4 (OR = 2.05; 95% CI, 1.19-3.51), and quintile 5 (OR = 2.13; 95% CI, 1.27-3.56) but not in quintile 3 (OR = 1.18; 95% CI, 0.67-2.10) as compared to never smokers in fully adjusted models. Former smokers had increased risk in quintile 2 (OR = 1.46; 95% CI, 1.00-2.12), quintile 3 (OR = 1.56; 95% CI, 1.09-2.24), quintile 4 (OR = 1.66; 95% CI, 1.13-2.42), and quintile 5 (OR = 1.73; 95% CI, 1.19-2.51), but not in quintile 1 (OR = 1.05; 95% CI, 0.72-1.55)., Conclusions: A nonlinear, V-shaped-like relationship between current cigarette smoking and plaque echodensity was observed. Former smokers were at the highest risk for plaques in high GSM quintiles. Thus, current smokers were more likely to have either soft or calcified plaques and former smokers were at greater risk of having only echodense plaques when compared to those who have never smoked. Further research is needed to determine if plaque morphology mediates an association between smoking and clinical vascular events., (© 2015 S. Karger AG, Basel.)

Liver transplantation (LT) has not traditionally been offered to patients with intracardiac shunts (ICSs) or pulmonary hypertension (PH). There is a paucity of data regarding cardiac structural characteristics in LT candidates. We examined echocardiographic characteristics and their role in managing LT candidates diagnosed with ICS and PH. We identified 502 consecutive patients (318 men, mean age 55 ± 11 years) who underwent LT and had preoperative echocardiogram. Demographics, cardiovascular risk factors, and echocardiographic variables were recorded and data were analyzed for end-stage liver disease diagnosis. ICSs were diagnosed with contrast echocardiography and PH was defined as estimated pulmonary artery systolic pressure >40 mm Hg. Primary end points included short-term (30-day) and long-term (mean 41-month) mortalities and the correlation between pre- and perioperative stroke. In our studied population >50% had >2 cardiovascular risk factors and with increasing frequency ICSs were diagnosed in 16%, PH in 25%, and intrapulmonary shunts in 41% of LT candidates. There was no correlation between short- and long-term mortality and ICS (p = 0.71 and 0.76, respectively) or PH (p = 0.79 and 0.71). Importantly, in those with ICS, no strokes occurred. In conclusion, structural differences exist between various end-stage liver disease diagnoses. ICSs diagnosed by echocardiography are not associated with an increased risk of perioperative stroke or increased mortality. A diagnosis of mild or moderate PH on baseline echocardiogram is not associated with worse outcomes and requires further assessment. Based on these findings, patients should not be excluded from consideration for LT based solely on the presence of an ICS or PH., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The number of foods available at a meal has been suggested as a major determinant of the amount consumed. Two studies conducted in humans test this idea by altering the number of foods available at a meal where participants eat the available foods ad libitum. In Study 1, dinner intake of twenty-seven young adults was measured. The amount consumed was measured when subjects were served either: (a) a composite meal (a protein rich food, a carbohydrate rich food, and a vegetable), (b) a low carbohydrate meal (protein rich food and vegetable), or (c) a vegetarian meal (carbohydrate rich food and vegetable). In Study 2, twenty-four subjects were given two different meals presented either as individual foods or as a composite meal (stir-fry or stew). Both studies show that the greater the number of foods offered at a meal, the greater the total intake. Study 2 demonstrated that the effects observed in Study 1 could not be attributed to different nutrient compositions, but was rather due to the presentation of the individual foods because the same foods that were offered as individual foods were combined to make the composite meal. The results demonstrate that the greater the number of foods offered at a meal, the greater the spontaneous intake of those foods. This finding is important because not only does it expand the concept of variety from the kinds of foods to the number of foods, but it presents an environmental variable that might contribute to overeating and obesity., (Copyright © 2012 Elsevier Ltd. All rights reserved.)