scholarly journals Pheochromocytoma Catecholamine Phenotypes and Prediction of Tumor Size and Location by Use of Plasma Free Metanephrines

2005 ◽  
Vol 51 (4) ◽  
pp. 735-744 ◽  
Author(s):  
Graeme Eisenhofer ◽  
Jacques WM Lenders ◽  
David S Goldstein ◽  
Massimo Mannelli ◽  
Gyorgy Csako ◽  
...  
Keyword(s):  
Tumor Size ◽  
Clinical Decision Making ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
High Plasma ◽  
Adrenal Tumors ◽  
Tumor Diameter ◽  
Urinary Catecholamines ◽  
Additional Information ◽  
Plasma Free Metanephrines

Abstract Background: Measurements of plasma free metanephrines (normetanephrine and metanephrine) provide a useful test for diagnosis of pheochromocytoma and may provide other information about the nature of these tumors. Methods: We examined relationships of tumor size, location, and catecholamine content with plasma and urinary metanephrines or catecholamines in 275 patients with pheochromocytoma. We then prospectively examined whether measurements of plasma free metanephrines could predict tumor size and location in an additional 16 patients. Results: Relative proportions of epinephrine and norepinephrine in tumor tissue were closely matched by relative increases of plasma or urinary metanephrine and normetanephrine, but not by epinephrine and norepinephrine. Tumor diameter showed strong positive relationships with summed plasma concentrations or urinary outputs of metanephrine and normetanephrine (r = 0.81 and 0.77; P <0.001), whereas relationships with plasma or urinary catecholamines were weaker (r = 0.41 and 0.44). All tumors in which increases in plasma metanephrine were >15% of the combined increases of normetanephrine and metanephrine either had adrenal locations or appeared to be recurrences of previously resected adrenal tumors. Measurements of plasma free metanephrines predicted tumor diameter to within a mean of 30% of actual diameter, and high plasma concentrations of free metanephrine relative to normetanephrine accurately predicted adrenal locations. Conclusions: Measurements of plasma free metanephrines not only provide information about the likely presence or absence of a pheochromocytoma, but when a tumor is present, can also help predict tumor size and location. This additional information may be useful for clinical decision-making during tumor localization procedures.

scholarly journals Plasma metanephrines and prospective prediction of tumor location, size and mutation type in patients with pheochromocytoma and paraganglioma

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Graeme Eisenhofer ◽  
Timo Deutschbein ◽  
Georgiana Constantinescu ◽  
Katharina Langton ◽  
Christina Pamporaki ◽  
...  
Keyword(s):  
Tumor Size ◽  
Clinical Decision Making ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Tumor Location ◽  
Other Information ◽  
Catecholamine Metabolites ◽  
Plasma Metanephrines ◽  
Plasma Free Metanephrines ◽  
Mutation Type

AbstractObjectivesPlasma free metanephrines are commonly used for diagnosis of pheochromocytoma and paraganglioma (PPGLs), but can also provide other information. This multicenter study prospectively examined whether tumor size, location, and mutations could be predicted by these metabolites.MethodsPredictions of tumor location, size, and mutation type, based on measurements of plasma normetanephrine, metanephrine, and methoxytyramine were made without knowledge of disease in 267 patients subsequently determined to have PPGLs.ResultsPredictions of adrenal vs. extra-adrenal locations according to increased plasma concentrations of metanephrine and methoxytyramine were correct in 93 and 97% of the respective 136 and 33 patients in who these predictions were possible. Predicted mean tumor diameters correlated positively (p<0.0001) with measured diameters; predictions agreed well for pheochromocytomas but were overestimated for paragangliomas. Considering only patients with mutations, 51 of the 54 (94%) patients with NF1 or RET mutations were correctly predicted with those mutations according to increased plasma metanephrine, whereas no or minimal increase in metanephrine correctly predicted all 71 patients with either VHL or SDHx mutations; furthermore, among the latter group increases in methoxytyramine correctly predicted SDHx mutations in 93% of the 29 cases for this specific prediction.ConclusionsExtents and patterns of increased plasma O-methylated catecholamine metabolites among patients with PPGLs allow predictions of tumor size, adrenal vs. extra-adrenal locations and general types of mutations. Predictions of tumor location are, however, only possible for patients with clearly increased plasma methoxytyramine or metanephrine. Where possible or clinically relevant the predictions are potentially useful for subsequent clinical decision-making.

Single-dose pharmacokinetics of orally administered terbinafine in bearded dragons (Pogona vitticeps) and the antifungal susceptibility patterns of Nannizziopsis guarroi

2021 ◽  
pp. 1-8
Author(s):  
Michael S. McEntire ◽  
Jennifer M. Reinhart ◽  
Sherry K. Cox ◽  
Krista A. Keller
Keyword(s):  
Single Dose ◽  
High Performance ◽  
Clinical Decision Making ◽  
Peak Plasma ◽  
Antifungal Susceptibility ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Oral Solution ◽  
Susceptibility Data ◽  
Pogona Vitticeps

Abstract OBJECTIVE To identify the antifungal susceptibility of Nanniziopsis guarroi isolates and to evaluate the single-dose pharmacokinetics of orally administered terbinafine in bearded dragons. ANIMALS 8 healthy adult bearded dragons. PROCEDURES 4 isolates of N guarroi were tested for antifungal susceptibility. A compounded oral solution of terbinafine (25 mg/mL [20 mg/kg]) was given before blood (0.2 mL) was drawn from the ventral tail vein at 0, 4, 8, 12, 24, 48, 72, and 96 hours after administration. Plasma terbinafine concentrations were measured with high-performance liquid chromatography. RESULTS The antifungal minimum inhibitory concentrations against N guarroi isolates ranged from 4,000 to > 64,000 ng/mL for fluconazole, 125 to 2,000 ng/mL for itraconazole, 125 to 2,000 ng/mL for ketoconazole, 125 to 1,000 ng/mL for posaconazole, 60 to 250 ng/mL for voriconazole, and 15 to 30 ng/mL for terbinafine. The mean ± SD peak plasma terbinafine concentration in bearded dragons was 435 ± 338 ng/mL at 13 ± 4.66 hours after administration. Plasma concentrations remained > 30 ng/mL for > 24 hours in all bearded dragons and for > 48 hours in 6 of 8 bearded dragons. Mean ± SD terminal half-life following oral administration was 21.2 ± 12.40 hours. CLINICAL RELEVANCE Antifungal susceptibility data are available for use in clinical decision making. Results indicated that administration of terbinafine (20 mg/kg, PO, q 24 to 48 h) in bearded dragons may be appropriate for the treatment of dermatomycoses caused by N guarroi. Clinical studies are needed to determine the efficacy of such treatment.

Serial plasma and CSF cell-free tumor DNA (cf-tDNA) tracking in diffuse midline glioma patients undergoing treatment with ONC201.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2012-2012
Author(s):  
Evan Cantor ◽  
Kyle Wierzbicki ◽  
Rohinton Tarapore ◽  
Chase Thomas ◽  
Rodrigo Cartaxo ◽  
...  
Keyword(s):  
Tumor Size ◽  
Clinical Decision Making ◽  
Phase 1 ◽  
Complete Response ◽  
Clinical Decision ◽  
Experimental Therapy ◽  
Plasma Samples ◽  
Mri Scans ◽  
Tumor Dna ◽  
Diffuse Midline Glioma

2012 Background: Diffuse midline glioma (DMG) with the H3K27M mutation is a lethal childhood brain cancer, with patients rarely surviving 2 years from diagnosis. There are few available means of monitoring the disease beyond serial MRI scans, making clinical decision making slow, difficult, and often reactive. Methods: We conducted a multi-site phase 1 trial of the imipridone ONC201 for children with H3K27M-mutant glioma (NCT03416530). Patients enrolled on Arm D of the trial (n=24) underwent serial lumbar puncture (baseline, 2 and 6 months) for cell-free tumor DNA (cf-tDNA) analysis at time of MRI. Additionally, patients on all arms of the trial at the University of Michigan underwent serial plasma collection. CSF collection was feasible in this cohort, with no procedural complications. We collected a total of 96 plasma samples and 53 CSF samples from 29 patients, including those with H3F3A (H3.3) (n=13), HIST13HB (H3.1) (n= 4), and unknown H3 status/not biopsied (n=12) [range of 0-8 CSF samples and 0-10 plasma samples]. We performed digital droplet polymerase chain reaction (ddPCR) analysis and/or amplicon-based electronic sequencing (Oxford Nanopore) of cf-tDNA samples and compared variant allele fraction (VAF) to radiographic change (maximal 2D tumor area on MRI). Results: Preliminary analysis of samples (n=58) demonstrates a correlation between changes in tumor size and H3K27M cf-tDNA VAF, when removing samples with concurrent bevacizumab. Analysis of remaining CSF and plasma samples is ongoing, including analysis of novel biomarkers of response. In multiple cases, early reduction in CSF cf-tDNA predicts long-term clinical response (>1 year) to ONC201 and does not increase in cases of later-defined pseudo-progression (radiation necrosis). For example, a now 9-year old patient with thalamic H3K27M-mutant DMG underwent treatment with ONC201 after initial radiation and developed an increase in tumor size at 4 months post-radiation (124% baseline) of unclear etiology at the time. Meanwhile, her ddPCR declined from baseline 6.76% VAF to <1%, which has persisted, with now near complete response (85% tumor reduction) at 30 months on treatment from diagnosis. Conclusions: In summary, we present the feasibility and utility of serial CSF/plasma monitoring of a promising experimental therapy for DMG.

scholarly journals Influence of psychiatric or social backgrounds on clinical decision making: a randomized, controlled multi-centre study

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yosuke Yamauchi ◽  
Takashi Shiga ◽  
Kiyoshi Shikino ◽  
Takahiro Uechi ◽  
Yasuaki Koyama ◽  
...  
Keyword(s):  
Decision Making ◽  
Repeated Measures ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Background Information ◽  
Accuracy Score ◽  
Multi Centre Study ◽  
Additional Information ◽  
Free Care ◽  
History Of

Abstract Background Frequent and repeated visits from patients with mental illness or free medical care recipients may elicit physicians’ negative emotions and influence their clinical decision making. This study investigated the impact of the psychiatric or social background of such patients on physicians’ decision making about whether to offer recommendations for further examinations and whether they expressed an appropriate disposition toward the patient. Methods A randomized, controlled multi-centre study of residents in transitional, internal medicine, or emergency medicine was conducted in five hospitals. Upon randomization, participants were stratified by gender and postgraduate year, and they were allocated to scenario set 1 or 2. They answered questions pertaining to decision-making based on eight clinical vignettes. Half of the eight vignettes presented to scenario set 1 included additional patient information, such as that the patient had a past medical history of schizophrenia or that the patient was a recipient of free care who made frequent visits to the doctor (biased vignettes). The other half included no additional information (neutral vignettes). For scenario set 2, the four biased vignettes presented to scenario set 1 were neutralized, and the four neutral vignettes were rendered biased by providing additional information. After reading, participants answered decision-making questions regarding diagnostic examination, interventions, or patient disposition. The primary analysis was a repeated-measures ANOVA on the mean management accuracy score, with patient background information as a within-subject factor (no bias, free care recipients, or history of schizophrenia). Results A total of 207 questionnaires were collected. Repeated-measures ANOVA showed that additional background information had influence on mean accuracy score (F(7, 206) = 13.84, p <  0.001 partial η2 = 0.063). Post hoc pairwise multiple comparison test, Sidak test, showed a significant difference between schizophrenia and no bias condition (p <  0.05). The ratings for patient likability were lower in the biased vignettes compared to the neutral vignettes, which was associated with the lower utilization of medical resources by the physicians. Conclusions Additional background information on past medical history of schizophrenia increased physicians’ mistakes in decision making. Patients’ psychiatric backgrounds should not bias physicians’ decision-making. Based on these findings, physicians are recommended to avoid being influenced by medically unrelated information.

Therapeutic Drug Monitoring of Imatinib and Impact on Clinical Decision Making.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4820-4820 ◽  
Author(s):  
Carolyn Blasdel ◽  
Yanfeng Wang ◽  
Theodore Lagattuta ◽  
Brian Druker ◽  
Laurie Letvak ◽  
...  
Keyword(s):  
Decision Making ◽  
Drug Monitoring ◽  
Dose Adjustment ◽  
Clinical Decision Making ◽  
Plasma Concentrations ◽  
Clinical Decision ◽  
Therapeutic Drug ◽  
Dose Increase ◽  
Qrt Pcr ◽  
Drug Concentrations

Abstract OBJECTIVES: Imatinib (IM) has demonstrated durable clinical efficacy in the majority of chronic myeloid leukemia (CML) patients. Optimal response may be influenced by multiple innate and external factors, some of which may be controlled by monitoring plasma concentrations of the drug. This abstract reports 6 cases where analyzing plasma IM trough concentrations (Cmin) in patients treated with three commonly used IM doses (400, 600, and 800 mg daily) influenced clinical decision making. METHODS: IM trough blood samples were collected at a time before that day’s IM dosing. Plasma concentrations of IM were determined by a validated LC/MS/MS method. RESULTS: In large population studies of CML patients enrolled in Phase I, II, and III clinical trials, the mean Cmin levels of IM at 400 mg qd, 600 mg qd, and 400 mg bid doses were: 981 (±543, 55%, n=394), 1572 (±1032, 66%, n=14), and 3479 (±1264, 36%, n=14) ng/mL, respectively. Large inter-patient variability was shown at all three doses. Of the 6 cases detailed in the table below, 4 (ID 1, 3, 4, and 5) had dose reduction due to tolerability concerns with subsequent improvement of symptoms following dose adjustment. One patient (ID 2) had a dose increase because of a poor qRT-PCR response. Another (ID 6) had a dose increase due to low plasma IM exposure resulting from drug-drug interaction with phenytoin, a known inducer of CYP3A4 (the major metabolizing isozyme for IM). After dose adjustment, all six patients showed good clinical response to IM treatment. The new mean Cmin value in these patients was 2000 (±471) ng/mL, representing a 24% coefficient of variability. CONCLUSIONS: Although the data is limited, IM drug monitoring proved useful in managing tolerability, lack of efficacy, adherence or potential drug interactions that modulate imatinib drug concentrations. More prospective studies are needed to demonstrate the value of IM drug monitoring in routine clinical practice. Patient ID Age, Sex CML Stage IM Daily Dose 1st Cmin (ng/mL) Reason for Dose Change New Dosing Regimen New Cmin (ng/mL) CP, chronic phase1 1 54, f CP 200 mg bid, Jan 03 3048, Sep 05 transfusion-dependent, anemia, Sep 05 300 mg, Oct 05 2130, Jan 06 2 9, f CP 300 mg, Jan 05 not done qRT-PCR 0.016, Jan 06 400 mg, Jan 06 2341, Jul 06 3 13, f CP 300 mg bid, May 05; 700 mg, Aug 05; 600 mg, Sep 05 1966, Feb 06 nausea, fatigue, arthralgias, myalgia, ongoing 400 mg, Mar 06 1222, May 06 4 67, f CP 400 mg, Feb 05 not done myelosuppression, Mar 05 200 mg, Mar 05 1928, May 06 5 53, f CP 400 mg, Apr 03; 600 mg, May 03; 800 mg, Jul 04 not done inflammatory pulmonary reaction with shortness of breath; dose held, Mar 05 400 mg, Oct 05 2378, May 06 6 73, m CP 350 mg, on phenytoin, Apr 99 35, Jun 99 stopped phenytoin, Jul 99 500 mg, Jul 99 not done; qRT-PCR negative, Jul 06

Total Amylase and Pancreatic Isoamylase in Serum and Urine: Considerations from Data on Biological Variation

1989 ◽  
Vol 26 (4) ◽  
pp. 335-340 ◽  
Author(s):  
Steven T Cummings ◽  
Callum G Fraser
Keyword(s):  
Clinical Decision Making ◽  
Amylase Activity ◽  
Clinical Decision ◽  
Population Based ◽  
Reference Intervals ◽  
Similar Data ◽  
Creatinine Ratio ◽  
Additional Information ◽  
Pancreatic Isoamylase ◽  
Urine Amylase

The analytical, within-subject and between-subject components of variation were estimated for amylase activity and pancreatic isoamylase activity in serum measured using newer analytical methods. Desirable analytical imprecisions based on within-subject variation were CV ≤ 4·4% and CV ≤ 7·0%, respectively. Conventional population-based reference intervals were not useful because of marked individuality; clinical decision-making points should be derived from the desired sensitivity and specificity. Serial results must change more than about 30% and 40% respectively before significance (P ≤ 0·05) can be claimed. Similar data on total amylase and pancreatic isoamylase activities in random and first morning urines showed that the use of conventional reference intervals was appropriate. Very large changes (> 100%) were required before a difference in serial results was significant. Calculation of the urine amylase/creatinine ratio appeared to confer no advantage. Derivation of the ratio of pancreatic isoamylase to total amylase activity in serum or urine was unlikely to provide additional information of value in either diagnosis or monitoring.

scholarly journals Utility and Acceptability of Influenza Surveillance amongst Emergency Providers

2015 ◽  
Vol 7 (1) ◽  
Author(s):  
Andrea F. Dugas ◽  
Howard Burkom ◽  
Anna L. DuVal ◽  
Richard Rothman
Keyword(s):  
Decision Making ◽  
Emergency Department ◽  
Real Time ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Surveillance Data ◽  
Influenza Surveillance ◽  
Additional Information ◽  
Provider Surveys

We provided emergency department providers with a real-time laboratory-based influenza surveillance tool, and evaluated the utility and acceptability of the surveillance information using provider surveys. The majority of emergency department providers found the surveillance data useful and indicated the additional information impacted their clinical decision making regarding influenza testing and treatment.

scholarly journals Prolactin ≤1 ng/mL predicts macroprolactinoma reduction after cabergoline therapy

2020 ◽  
Vol 182 (2) ◽  
pp. 177-183
Author(s):  
Daham Kim ◽  
Cheol Ryong Ku ◽  
Kyungwon Kim ◽  
Hyein Jung ◽  
Eun Jig Lee
Keyword(s):  
Tumor Size ◽  
Prolactin Level ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Post Treatment ◽  
Size Reduction ◽  
Multivariable Logistic Regression Analysis ◽  
High Dose ◽  
Pituitary Hormone ◽  
Level 1

Objective The association between prolactin level variation and prolactinoma size reduction remains unclear. This study aimed to determine the prolactin level cut-off predictive of a tumor size reduction. Design Retrospective cohort study. Methods We reviewed medical records of patients with prolactinoma who received primary cabergoline therapy and for whom complete data on pituitary hormone assays and sellar MRI at baseline and 3 months post treatment were available. We tested whether the certain prolactin level after 3 months post treatment predicted better response. Results Prolactin levels normalized in 109 (88.6%) of 123 included macroprolactinoma patients. The mean tumor size reduction was 22.9%, and patients in the lowest prolactin tertile (≤0.7) had the highest frequency of tumor size reductions of ≥20% (73.7 vs 52.9% and 45.9% in tertiles 2 (>0.7 to 2.6) and 3 (>2.6 to 20), P = 0.015). Patients with prolactin levels ≤1 ng/mL exhibited larger tumor size reductions vs those with prolactin levels of 1–20 (27.2 ± 18.3% vs 19.5 ± 13.9%, P = 0.014), 1–10 (19.3 ± 13.7%, P = 0.017) and 1–5 ng/mL (19.2 ± 14.3%, P = 0.039). A multivariable logistic regression analysis revealed that a prolactin level ≤1 ng/mL at 3 months and high-dose cabergoline therapy were significantly associated with tumor size reductions of ≥20% (odds ratio (OR): 2.8, 95% confidence interval (CI): 1.2–6.7, P = 0.017; OR: 2.0, 95% CI: 1.0–3.9, P = 0.043). Conclusions A prolactin level ≤1 ng/mL at 3 months after cabergoline treatment was correlated with a significant tumor size reduction in patients with macroprolactinoma. This finding may help clinical decision making when treating macroprolactinoma patients.

The impact of tumor size on survival in T3 non-small cell lung-cancer with direct extension.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20033-e20033
Author(s):  
Clara H. Kim ◽  
Michelle C. Salazar ◽  
Jessica R. Hoag ◽  
Joshua E. Rosen ◽  
Brian N. Arnold ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Tumor Size ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Adjuvant Chemoradiation ◽  
Direct Extension ◽  
Cox Proportional Hazard Models ◽  
N Stage ◽  
The Impact

e20033 Background: Tumor size is an important prognostic variable that affects clinical decision-making in NSCLC including the use of adjuvant therapy. However, the association between tumor size and survival in a subset of patients who have T3 NSCLC with direct extension into nearby structures (T3dx) has not been explicitly characterized. We hypothesize that tumor size impacts survival and prognosis within this cohort. Methods: Patients with T3dxin 2006-2013 who underwent lobectomy or pneumonectomy were identified in the National Cancer Database. Patients who received neoadjuvant therapy or had positive margins were excluded. Tumor size was categorized based on cutoffs used by current staging guidelines and patients were stratified by pathologic N stage (see table). Cox proportional hazard models were used to measure the independent impact of tumor size on survival. Results: Overall, 0.1-3cm tumors exhibit superior 5-year survival compared to 3.1-5cm and >5cm tumors. Tumor size is significantly associated with survival in N0 patients but not in N1 and N2 patients. Use of adjuvant chemotherapy is associated with improved survival in the overall cohort and all subgroups; however, use of adjuvant chemoradiation may be associated with inferior survival in the overall cohort. Conclusions: Larger tumor size is associated with inferior survival in T3dx in the absence of nodal disease. T3dx requires a more tailored approach to adjuvant therapy than other T3 subgroups. Adjuvant chemotherapy appears to benefit all patients with T3dx; however, the role of adjuvant chemoradiation is less clear. [Table: see text]

scholarly journals Using daily monitoring of psychiatric symptoms to evaluate hospital length of stay

BJPsych Open ◽  
2016 ◽  
Vol 2 (6) ◽  
pp. 341-345 ◽  
Author(s):  
Andrew C. Page ◽  
Nadia K. Cunningham ◽  
Geoffrey R. Hooke
Keyword(s):  
Hospital Stay ◽  
Clinical Decision Making ◽  
Psychiatric Symptoms ◽  
Clinical Decision ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Significant Treatment ◽  
Daily Monitoring ◽  
Additional Information ◽  
Clinically Significant

BackgroundRoutine symptom monitoring and feedback improves out-patient outcomes, but the feasibility of its use to inform decisions about discharge from in-patient care has not been explored.AimsTo examine the potential value to clinical decision-making of monitoring symptoms during psychiatric in-patient hospitalisation.MethodA total of 1102 in-patients in a private psychiatric hospital, primarily with affective and neurotic disorders, rated daily distress levels throughout their hospital stay. The trajectories of patients who had, and had not, met a criterion of clinically significant improvement were examined.ResultsTwo-thirds of patients (n=604) met the clinically significant improvement criterion at discharge, and three-quarters (n=867) met the criterion earlier during their hospital stay. After meeting the criterion, the majority (73.2%) showed stable symptoms across the remainder of their hospital stay, and both classes showed substantially lower symptoms than at admission.ConclusionsMonitoring of progress towards this criterion provides additional information regarding significant treatment response that could inform clinical decisions around discharge readiness.

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