Citations

PURPOSE Electronic health records (EHRs) are created primarily for nonresearch purposes; thus, the amounts of data are enormous, and the data are crude, heterogeneous, incomplete, and largely unstructured, presenting challenges to effective analyses for timely, reliable results. Particularly, research dealing with clinical notes relevant to patient care and outcome is seldom conducted, due to the complexity of data extraction and accurate annotation in the past. RECIST is a set of widely accepted research criteria to evaluate tumor response in patients undergoing antineoplastic therapy. The aim for this study was to identify textual sources for RECIST information in EHRs and to develop a corpus of pharmacotherapy and response entities for development of natural language processing tools. METHODS We focused on pharmacotherapies and patient responses, using 55,120 medical notes (n = 72 types) in Mayo Clinic’s EHRs from 622 randomly selected patients who signed authorization for research. Using the Multidocument Annotation Environment tool, we applied and evaluated predefined keywords, and time interval and note-type filters for identifying RECIST information and established a gold standard data set for patient outcome research. RESULTS Key words reduced clinical notes to 37,406, and using four note types within 12 months postdiagnosis further reduced the number of notes to 5,005 that were manually annotated, which covered 97.9% of all cases (n = 609 of 622). The resulting data set of 609 cases (n = 503 for training and n = 106 for validation purpose), contains 736 fully annotated, deidentified clinical notes, with pharmacotherapies and four response end points: complete response, partial response, stable disease, and progressive disease. This resource is readily expandable to specific drugs, regimens, and most solid tumors. CONCLUSION We have established a gold standard data set to accommodate development of biomedical informatics tools in accelerating research into antineoplastic therapeutic response.

Purpose: To evaluate spectral domain optical coherence tomography (SD-OCT) features of vitreoretinal lymphoma (VRL). Methods: Review of records and SD-OCT images of vitreoretinal lymphoma evaluated at Ocular Oncology Service, Wills Eye Hospital between July 1, 2000, and April 1, 2019. Results: There were 55 eyes of 32 patients included. At presentation, SD-OCT features included vitreous opacities (n = 36, 65%), preretinal deposits (n = 7, 13%), intraretinal deposits (n = 8, 15%), subretinal deposits (n = 20, 36%), retinal pigment epithelium abnormalities (n = 35, 64%), and subretinal pigment epithelium deposits (n = 35, 64%). Of 36 eyes with observed tumor progression, comparison (initial visit vs. time of progression) revealed more intraretinal deposits (17% vs. 50%, P = 0.005) at progression. Of 15 eyes with tumor recurrence, comparison (initial visit vs. time of recurrence) revealed more intraretinal deposits (7% vs. 47%, P = 0.04) at recurrence. At last visit, 39 eyes demonstrated tumor regression. By comparison (initial presentation vs. regression), there were less frequent vitreous opacities (67% vs. 0%, P < 0.001), intraretinal deposits (15% vs. 0%, P = 0.03), subretinal deposits (36% vs. 0%, P < 0.001), and subretinal pigment epithelium deposits (69% vs. 21%, P < 0.001) at regression. Conclusion: Using SD-OCT in patients with vitreoretinal lymphoma, local tumor regression correlated with a reduction in vitreous opacities, intraretinal deposits, subretinal deposits, and subretinal pigment epithelium deposits. SD-OCT is useful in judging vitreoretinal lymphoma response to therapy.

The relationship between selenium and metabolic syndrome (MetS) has been discussed controversially, and limited studies have examined the associations of single nucleotide polymorphisms in selenoproteins genes with MetS. Hence, to examine the associations of plasma selenium concentrations and selenoprotein P rs7579 polymorphism with MetS, a case-control study of 1279 MetS cases and 1279 sex- and age- (±2 years) matched controls was conducted based on the baseline data of the Tongji-Ezhou Cohort study. Plasma selenium concentrations were measured by inductively coupled plasma mass spectrometry. MetS was defined using the definition of the Joint Interim Statement, adjusted for the Chinese population. In addition, the rs7579 polymorphism was genotyped by the Agena MassARRAY System. Plasma selenium concentrations in the MetS group were higher than in the control group (93.88 μg/L (83.17-107.41) vs. 92.66 μg/L (82.36-103.53), P<0.05). Compared with quartile 4 (≥103.53 μg/L), the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) associated with MetS were 0.79 (0.59-1.06) for quartile 1 (<82.36 μg/L), 0.75 (0.56-1.01) for quartile 2 (82.37-92.66 μg/L), and 0.61 (0.45-0.83) for quartile 3 (92.67-103.52 μg/L). The cubic spline analyses revealed a U-shaped association between plasma selenium and MetS, with the lowest risk at around 93.69 μg/L. Moreover, in cubic spline analyses, plasma selenium showed U-shaped associations with central obesity and high blood pressure, positive associations with hypertriglyceridemia and hyperglycemia, and a negative association with low high-density lipoprotein cholesterol. Additionally, both the GA and GA+AA genotype carriers were associated with increased ORs of MetS comparing with the GG genotype carriers. Our findings suggested a U-shaped association between plasma selenium and MetS and diverse associations between plasma selenium and components of MetS. Furthermore, our study found that the A allele of rs7579 was associated with higher odds of MetS. Further studies are needed to confirm our findings and elucidate the underlying mechanisms.

Abstract We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.

Abstract Background Hypothyroidism is known to be associated with adverse clinical outcomes in heart failure. The association between hypothyroidism and cardiac resynchronization therapy outcomes in patients with severe heart failure is not clear. Methods The study included 1,316 patients who received cardiac resynchronization therapy between 2002 and 2015. Baseline demographics and cardiac resynchronization therapy outcomes, including left ventricular ejection fraction, New York Heart Association class, appropriate implantable cardioverter-defibrillator therapy, and all-cause mortality, were collected from the electronic health record. Results Of the study cohort, 349 patients (26.5%) were classified as the hypothyroidism group. The median duration of follow-up was 3.6 years (interquartile range, 1.7-6.2). Hypothyroidism was associated with a greater all-cause mortality than euthyroidism (hazard ratio, 1.19; 95% CI, 1.01-1.38; P=0.04). In this group, the risk of appropriate implantable cardioverter-defibrillator therapy significantly increased in association with increased baseline thyroid-stimulating hormone level (hazard ratio, 1.27 per 5 mIU/L increase, 95% CI, 1.00-1.53, P=0.04). Conclusions Cardiac resynchronization therapy improves cardiac function in hypothyroid patients. Hypothyroidism has adverse effects on cardiac resynchronization therapy outcomes with reduced survival and increased implantable cardioverter-defibrillator therapies for ventricular arrhythmic events.

Abstract BACKGROUND. Several studies have recently reported on the occurrence of a JAK2 V617F mutation in myeloid cells from the majority of patients with polycythemia vera (PV). The clinical relevance of this novel observation is currently under study. Similarly, there is limited information regarding the correlation of JAK2 V617F mutational status and neutrophil PRV-1 transcript level in PV, secondary polycythemia (SP) and other myeloproliferative disorders (MPD). METHODS. In a single institutional study, mutation screening for JAK2 V617F was performed in DNA derived from archived blood granulocytes from 63 consecutive patients with PV in whom current diagnostic criteria were strictly applied and diagnosis confirmed by bone marrow histology. Concomitant quantitative analysis of neutrophil PRV-1 expression was performed in 28 of the 63 patients and the results of both JAK2 V617F and PRV-1 analysis in these 28 patients were compared with those from another 22 patients with essential thrombocythemia (ET), 10 with myelofibrosis with myeloid metaplasia (MMM), 19 with SP, and 11 healthy volunteers. RESULTS. The 63 patients with PV were followed for a median of 33 months (range 3–324) from the time of initial diagnosis. During this period, 3 patients have died including 2 from acute myeloid leukemia (AML). Disease transformation into either AML or MMM has occurred in 2 and 4 patients, respectively. The median time from diagnosis to the time of mutation analysis was 12 months (range 0–306). JAK2 V617F was detected in 58 of the 63 patients with PV (92%; homozygous in 21%). The clinical phenotype of the 5 patients with wild-type allele was otherwise typical for the disease. A statistical comparison between JAK2 V617F heterozygotes (n=45) and homozygotes (n=13) in PV did not reveal significant associations in regards to age, gender, leukocyte or platelet count at diagnosis, disease duration, or the incidences of thrombosis or bleeding. However, JAK2 V617F homozygotes, compared to their heterozygote counterparts, displayed significantly higher hemoglobin level at diagnosis (p=0.001), increased incidence of pruritus (69% vs. 38%; p=0.04), and a higher rate of fibrotic transformation (23% vs. 2%; p=0.009). The overall (homozygous) JAK2 V617F mutational frequencies in the other study patients with ET, MMM, SP, and healthy controls were 55% (0%), 30% (0%), 0%, and 0%, respectively. The corresponding figures for increased PRV-1 expression in these patients were 18%, 20%, 21%, and 9% as compared to 89% in PV. In patients with either ET or MMM, the likelihood of detecting JAK2 V617F was significantly higher in the presence of an increased PRV-1 expression (83% vs. 38%; p=0.05). Similarly, in patients with PV, homozygous as compared to heterozygous JAK2 V617F correlated with higher levels of PRV-1 expression (p=0.07). CONCLUSIONS. The current clinical study demonstrates a mutant allele dose effect on erythrocytosis, PV-characteristic clinical features, and granulocyte PRV-1 expression in PV. Furthermore, compared to the PRV-1 assay, mutation screening for JAK2 V617F displayed greater specificity in distinguishing PV from SP.

Abstract Background: Allogeneic hematopoietic stem cell transplantation is potentially curative in agnogenic myeloid metaplasia (AMM) but is associated with substantial mortality and morbidity that necessitates accurate identification of patients in whom benefit outweighs risk. The current single institutional study investigates prognostic variables in transplant-eligible patients with AMM with the main objective of improved discrimination between intermediate- and high-risk patient categories. Methods: Patients diagnosed with AMM before the age of 60 years and seen at Mayo Clinic were identified and the diagnosis confirmed. Relevant demographic, clinical and laboratory characteristics were abstracted and the impact of various parameters on overall survival was evaluated with univariate and multivariate analysis. Results: A cohort of 159 patients (median age 52 years, range 18–60; 89 males) with AMM is described. Median follow-up from initial diagnosis was 63 months (range 0–300). During this period, 102 patients have died; overall median survival 79 months. Multivariate analysis of parameters measured in all study patients at diagnosis identified thrombocytopenia (platelet count &lt; 100 x 109/L) as the strongest predictor of inferior survival (p=0.002). In addition, a hemoglobin level of &lt;10 g/dL (p=0.003), white blood cell count of either &lt;4 or &gt;30 x 109/L (p=0.03), and older age (p=0.02) were also found to be independent indicators of poor prognosis. However, when the analysis included parameters that were measured in variable proportion of the study population, the independent prognostic factors for poor survival were thrombocytopenia (p=0.0001), anemia (p=0.01), and the presence of unfavorable cytogenetic abnormalities (0.001). Based on the above findings, we constructed a new complete blood count (CBC)-based prognostic scoring system (Figure 1) that performed better than the Dupriez scoring system in discriminating intermediate- from high-risk patient categories(Figure 2). Figure Figure Conclusions: Thrombocytopenia is a strong predictor of poor survival in transplant-eligible patients with AMM. The incorporation of platelet count into the Dupriez prognostic scoring system might allow the construction of an improved, CBC-based scoring system that can accurately identify high-risk as well as intermediate-risk patients with AMM.

Abstract Post-polycythemic (PPMM) and post-thrombocythemic (PTMM) myeloid metaplasia are consensually referred to as secondary myelofibrosis (sMF). Prognostic variables in sMF are not as well defined as they are for agnogenic myeloid metaplasia (AMM). Such information is particularly crucial for management decisions in transplant-eligible patients. Accordingly, we examined the prognostic impact of several clinical and laboratory variables in 66 young patients (age &lt; 60 years) with sMF including 37 with PPMM and 29 with PTMM. Multivariate analysis of parameters other than cytogenetics identified older age (p=0.02), anemia (hemoglobin level &lt; 10 g/dL; p=0.007), and PPMM (p=0.009) as independent risk factors for shortened survival. However, when such analysis was restricted to patients in whom cytogenetic studies were performed (n=31), the presence of unfavorable cytogenetic abnormalities (i.e. clones other than 20q- and 13q-) became the one and only adverse prognostic factor for survival (p=0.001). Figure Figure The prognostic value of cytogenetics was independent of the Dupriez prognostic score (p=0.003). Figure Figure A similar analysis in a temporal cohort of 50 age-matched patients with AMM also identified unfavorable cytogenetics as an independent predictor of poor survival along with thrombocytopenia and anemia. The current study suggests an important prognostic role for cytogenetics in both de novo and secondary myelofibrosis.