Citations

Abstract The syndrome of episodic angioedema and eosinophilia is characterized by cyclic edema, marked peripheral blood eosinophilia, and eosinophil degranulation in the dermis. Using a sensitive immunoenzymetric method, we measured serum interleukin (IL)-5 levels in four patients with this syndrome. We also determined the percentage of activated T cells in the peripheral blood of a new patient before and during an attack. In the patient presented, IL-5 levels peaked several days before maximal eosinophilia and then declined. This patient's lymphocytes showed an increased percentage, 28% (normal 2% to 3%), of activated T cells staining for both CD3 and HLA-DR 10 days before maximal eosinophilia, but no increase at the time of peak eosinophilia. In serum from three previously reported cases, elevated serum IL-5 levels were found during attacks. After glucocorticoid administration, IL-5 levels became undetectable in three of the four patients. Production of IL-5 is likely an important determinant of the pathophysiology of this syndrome.

The syndrome of episodic angioedema and eosinophilia is characterized by cyclic edema, marked peripheral blood eosinophilia, and eosinophil degranulation in the dermis. Using a sensitive immunoenzymetric method, we measured serum interleukin (IL)-5 levels in four patients with this syndrome. We also determined the percentage of activated T cells in the peripheral blood of a new patient before and during an attack. In the patient presented, IL-5 levels peaked several days before maximal eosinophilia and then declined. This patient's lymphocytes showed an increased percentage, 28% (normal 2% to 3%), of activated T cells staining for both CD3 and HLA-DR 10 days before maximal eosinophilia, but no increase at the time of peak eosinophilia. In serum from three previously reported cases, elevated serum IL-5 levels were found during attacks. After glucocorticoid administration, IL-5 levels became undetectable in three of the four patients. Production of IL-5 is likely an important determinant of the pathophysiology of this syndrome.

AbstractNerve growth factor (NGF ) can influence mast cell development and function in murine rodents by interacting with its receptors on mast cells. We now report the identification of mRNA transcripts of full-length tyrosine kinase-containing trkA, trkB, and trkC neurotrophin receptor genes in HMC-1 human mast cell leukemia cells. Although HMC-1 cells lacked p75 mRNA, they expressed transcripts for the exon-lacking splice variant of trkA (trkAI), truncated trkB (trkB.T1), and truncated trkC. By flow cytometry, HMC-1 cells exhibited expression of TrkA, TrkB, and TrkC receptor proteins containing full-length tyrosine kinase domains. NGF stimulation of HMC-1 cells induced tyrosine phosphorylation of TrkA protein, increased expression of the early response genes c-fos and NGF1-A, and activation of ERK-mitogen–activated protein (MAP) kinase, results which indicate that TrkA receptors in HMC-1 cells are fully functional. Highly purified populations of human lung mast cells expressed mRNAs for trkA, trkB and trkC, whereas preparations of human umbilical cord blood-derived mast cells expressed mRNAs for trkA and trkC, but not trkB. Moreover, preparations of human umbilical cord blood-derived immature mast cells not only expressed mRNA transcript and protein for TrkA, but exhibited significantly higher numbers of chymase-positive cells after the addition of NGF to their culture medium for 3 weeks. In addition, HMC-1 cells expressed mRNAs for NGF, brain-derived neurotrophic factor (BDNF ), and neurotrophin-3 (NT-3), the cognate ligands for TrkA, TrkB, and TrkC, whereas NGF and BDNF transcripts were detectable in human umbilical cord blood mast cell preparations. Taken together, our findings show that human mast cells express a functional TrkA receptor tyrosine kinase and indicate that NGF may be able to promote certain aspects of mast cell development and/or maturation in humans. Our studies also raise the possibility that human mast cells may represent a potential source for neurotrophins.

Abstract Background: Blood eosinophilia results either from autonomous expansion of a myeloid stem/progenitor cell, or as a response to cytokines that promote growth and differentiation of eosinophil progenitors. A subset of patients with hypereosinophilic syndrome/idiopathic eosinophilia (HES/IE) display abnormal T-cell immunophenotype and/or clonal rearrangements of the T-cell receptor (TCR), operationally assigned the term “lymphocyte variant” HES/IE. Information on the prevalence, FIP1L1-PDGFRA status, and clinical course of such patients is limited. Methods: Consecutive patients with eosinophilia were identified by querying our institutional electronic database from 1995 to 2004. Clonal rearrangements of the γchain of the TCR were identified by polymerase chain reaction followed by gel electrophoresis in all cases, and confirmed by Southern Blot analysis of the gene coding for the β chain of the TCR, using standard methods. FIP1L1-PDGFRA was screened by fluorescence in situ hybridization. Results: We studied a total of 205 consecutive patients with eosinophilia defined as an absolute eosinophil count (AEC) of > 600/μL, who also had a bone marrow study performed. Of these, TCR gene rearrangements studies were performed in 99 patients (AEC range of 650 to 38,000/μL) including 3 children and 96 adults (age range 18 to 88 years; 58 males). Among these 99 patients, 14 (~14%) had a demonstrable T-cell clone in peripheral blood, bone marrow aspirate, lymph node, and/or skin. Six of the 14 patients with a demonstrable T-cell clone were found to have a concurrent T-cell malignancy at the time of evaluation including T-cell large granular lymphocytic (T-LGL) leukemia - 1 case and peripheral T-cell lymphoma - 5 cases. The other 8 (~8%) patients otherwise fulfilled the working diagnosis of “lymphocyte variant” HES/IE (median AEC=2045/μL, range 720/μL to 9600/μL). The median duration of eosinophilic prodrome, prior to identification of the occult T-cell clone was 5 years (range 3 months to 11 years), and virtually all had dominant skin involvement presenting as dermatitis (5 cases) or episodic angioedema with eosinophilia (EAE) (2 cases). Five of 7 patients tested had an elevated serum IgE level, and a similar proportion displayed an abnormal T-cell immunophenotype (most commonly, aberrant CD5 and/or CD7 expression). Six of the 8 patients with an occult T-cell clone were evaluated for FIP1L1-PDGFRA and tested negative. Two patients were effectively treated with low-dose oral cyclophosphamide or methotrexate (follow-up duration of 3+ and 6+ years, respectively) whereas imatinib treatment was ineffective in another 2 patients. Two patients (25%) transformed into cutaneous T-cell lymphoma after 3 to 8 years of eosinophilic prodrome. Conclusion: The current study suggests that the presence of a T-cell clone in idiopathic eosinophilia is a marker/harbinger of a primarily skin-based peripheral T-cell lymphoma that responds to T cell-directed therapy but not imatinib therapy, which is consistent with the absence of FIP1L1-PDGFRA in such cases.

Background Health care disparities in Appalachia are well documented. However, no previous studies have examined possible differences in the utilization of breast reconstruction (BR) in Appalachia. This study aims to determine if a disparity in BR utilization exists in women from Appalachia Kentucky. Methods A retrospective, population-based cohort study was conducted from January 1, 2006, to December 31, 2015. The Kentucky Cancer Registry was queried to identify population-level data for female patients diagnosed with breast cancer and treated with mastectomy. A multivariate logistic regression model controlling for patient, disease, and treatment characteristics was constructed to predict the likelihood of BR. Results Bivariate testing showed differences (P < 0.0001) in BR utilization between Appalachian and non-Appalachian women in Kentucky (15.0% and 26.3%, respectively). Multivariate analysis showed that women from Appalachia (odds ratio, 0.54; confidence interval (95), 0.48–0.61; P < 0.0001) were less likely to undergo BR than non-Appalachian women. Interestingly, the rate of BR increased over time in both Appalachian (r = 0.115; P < 0.0001) and non-Appalachian women (r = 0.148; P < 0.0001). Conclusions Despite the benefits of BR, women from Appalachia undergo BR at lower rates and are less likely to receive BR than non-Appalachian Kentuckians. Although the rates of BR increased over time in both populations, access to comprehensive breast cancer care remains a challenge for women from Kentucky's Appalachian region.

Objectives (1) To perform a systematic literature review to evaluate associations between post‐dural puncture headache (PDPH) and opening pressure (OP), closing pressure (CP), and volume of cerebrospinal fluid (V) removed. (2) To perform a case‐control study to evaluate pressure‐volume index (PVI) as a novel risk factor for PDPH. Background According to the International Classification of Headache Diagnoses, 3rd Edition (ICHD‐3), the diagnosis of PDPH requires documentation of intracranial hypotension. However, this remains an unproven concept. Methods A systematic literature review was conducted, searching Cochrane Database of Systematic Reviews, Ovid EMBASE, OVID MEDLINE, Scopus, and Web of Science. Study inclusion required a comparison of headache incidence following a LP as a function of OP, CP, and/or V. A retrospective, case‐control study with 1:1 matching was conducted utilizing ICHD‐3 criteria. Patients with factors that could influence CSF pressure were excluded. Results In our case‐control study, we did not identify a paired difference in either median (95% CI) elastance (0.05 [−0.09, 0.11], P = .503) or PVI (4.53 [−7.98, 19.97], P = .678). We identified 22 references, evaluating V (n = 14), OP (n = 11), and/or CP (n = 4). There was no convincing evidence for an association of PDPH with either OP or CP. A minority of studies documenting an association with V included patients with high‐volume CSF removal, and/or stratified patients by the timing of the headache onset. Conclusions The overall risk of PDPH does not appear to be influenced by OP, CP, V or PVI. PDPH may be related to V in instances of high‐volume removal, and depend on the timing of outcome assessment. Future revision of criteria should consider the existence of immediate and delayed PDPH subtypes, and not presume intracranial hypotension as a mandatory feature.

Abstract Background Guidelines to provide recommendations about driving restrictions for patients with brain metastases are lacking. We aim to determine whether clinical neurologic examination is sufficient to predict suitability to drive in these patients by comparison with an occupational therapy driving assessment (OTDA). Methods We prospectively evaluated the concordance between neurology assessment of suitability to drive (pass/fail) and OTDA in 41 individuals with brain metastases. Neuro-oncology evaluation included an interview and neurological examination. Participants subsequently underwent OTDA during which a battery of objective measures of visual, cognitive, and motor skills related to driving was administered. Results The mean age of patients who failed OTDA was age 68.9 years vs 59.3 years in the group members who passed (P = .0046). The sensitivity of the neurology assessment to predict driving fitness compared with OTDA was 16.1% and the specificity 90%. The 31 patients who failed OTDA were more likely to fail Vision Coach, Montreal Cognitive Assessment, and Trail Making B tests. Conclusions There was poor association between the assessment of suitability to drive by neurologists and the outcome of the OTDA in patients with brain metastases. Subtle deficits that may impair the ability to drive safely may not be evident on neurologic examination. The positive predictive value was high to predict OTDA failure. Age could be a factor affecting OTDA performance. The results raise questions about the choice of assessments in making recommendations about driving fitness in people with brain metastases. OTDA should be strongly considered in patients with brain metastases who wish to continue driving.

5063 Background: The systemic therapies available to patients with metastatic prostate cancer (mPC) have improved dramatically over the past decade. Prior to 2010, the only agents with a proven survival benefit for patients with metastatic disease were androgen deprivation therapy and docetaxel. Since then, five new agents have been FDA approved and have proven survival benefit in phase III trials. Anecdotal experience suggests that the increased available lines of therapy have changed the profile of mPC to include a higher prevalence of visceral metastases. Methods: A retrospective review of 474 patients with prostate cancer who died in 2009 and in 2016 was performed. Patients with metastatic disease who had imaging within 6 months of death were included. A total of 164 patients were eligible for analysis. Results: Mean age at death overall was 77.4 years (SD 9.5) and did not differ signifiantly by cohort. Overall rates of visceral and distant metastases to include lung, liver, adrenal, brain, renal, spleen, and thyroid, were higher in patients who died in 2016 as compared to those who died in 2009 (40.0% and 26.1%, respectively, p = 0.07). Lung metastases were more prevalent in patients who died in 2016 versus in 2009 at 26.3% and 13.0%, respectively (p = 0.05). Patients who died in 2009 received a median of 3 (range 1-10) systemic treatments versus 4 (range 0-13) in those who died in 2016 (p = 0.005). Forty-four percent of patients who died in 2016 used five or more lines of systemic treatments compared to 26.1% of patients in 2009. Conclusions: The emergence of new systemic therapies for mPC is changing the natural history of the disease. Forty percent of patients now develop visceral metastases compared to 26% in the past. These changes will drive the need for new treatment approaches targeting visceral metastases. [Table: see text]

Abstract Background Women may benefit from radial artery access (RAA) for percutaneous coronary interventions (PCI) due to a higher risk of bleeding compared to men; however, RAA may be underutilized in women. We sought to determine the frequency and predictors of RAA use in patients undergoing PCI. Methods We studied 21,123 (29.0% female) participants in the Mayo Clinic PCI Registry from January 1, 2006–December 31, 2016. Data were analyzed as a cohort and by time tertiles. Frequency of RAA versus femoral access and bleeding events were recorded. Logistic regression was used to identify predictors of RAA. Results In the overall cohort, women compared to men were older (69.6 ± 12.6 vs. 65.6 ± 11.9; p < .001), more likely to present with acute coronary syndrome (82.0% in women vs. 80.0% in men; p = .0008) and had more comorbidities. RAA increased from tertile one (3.5% for women vs. 4.0% for men; p = .3) through tertile three (46.8% for women vs. 50.3% for men; p = .01), but remained lower in women. In multivariable analysis, female sex is associated with 22% less RAA use (OR 0.78, 95% CI 0.72–0.84; p < .0001). Women compared to men experienced more bleeding (6.3 vs. 3.0%; p < .0001) but bleeding was less likely in RAA (OR 0.45, 95% CI 0.36–0.56; p < .0001). Conclusion Women undergoing PCI are less likely to receive RAA compared to men despite having a higher risk of bleeding. This trend persists despite increase in RAA use. Given the potential benefit of RAA in women, sex should be considered in patient selection for RAA.