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Prospective Comparison of PET Imaging with PSMA-Targeted 18F-DCFPyL Versus Na18F for Bone Lesion Detection in Patients with Metastatic Prostate Cancer.
Rowe, SP, Li, X, Trock, BJ, Werner, RA, Frey, S, DiGianvittorio, M, Bleiler, JK, Reyes, DK, Abdallah, R, Pienta, KJ, et al
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2020;(2):183-188
Abstract
Bone metastases in prostate cancer (PCa) have important prognostic significance, and imaging modalities used for PCa staging should have high sensitivity for detecting such lesions. Prostate-specific membrane antigen (PSMA)-targeted PET radiotracers are promising new agents for imaging PCa. We undertook a head-to-head comparison of PSMA-targeted 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) PET to Na18F PET to determine which modality was more sensitive for the detection of lesions suggestive of bone metastases in a group of patients with metastatic PCa. Methods: Patients with progressive, metastatic PCa were prospectively imaged with both 18F-DCFPyL and Na18F PET/CT, with both scans occurring within 24 h of each other. A consensus 2-reader central review was performed to identify all bone lesions suggestive of sites of PCa involvement on both scans, and maximized SUVs corrected for body weight (SUVmax) and lean body mass (SULmax) were recorded. Soft-tissue lesions were also noted on both scans, and SUVmax, SULmax, and PSMA reporting and data system (RADS) version 1.0 scores were recorded. Data from the 2 scans were compared using a generalized estimating equation. Results: In total, 16 patients meeting all inclusion criteria were enrolled in this study, and 15 of the 16 (93.8%) were imaged with both PET radiotracers. In total, 405 bone lesions suggestive of sites of PCa were identified on at least 1 scan. On 18F-DCFPyL PET/CT, 391 (96.5%) were definitively positive, 4 (1.0%) were equivocally positive, and 10 (2.5%) were negative. On Na18F PET/CT, the corresponding values were 388 (95.8%), 4 (1.0%), and 13 (3.2%). Of the definitively negative lesions on 18F-DCFPyL PET, 8 of 10 (80.0%) were sclerotic and 2 of 10 (20.0%) were infiltrative or marrow-based. Additionally, 12 of 13 (92.3%) of the definitively negative lesions on Na18F PET were infiltrative or marrow-based and 1 of 13 (7.7%) was lytic. Also identified were 78 PSMA-RADS-4, 17 PSMA-RADS-5, and 1 PSMA-RADS-3C soft-tissue lesions. Conclusion: PET/CT imaging using 18F-DCFPyL and Na18F PET had nearly identical sensitivities for the detection of bone lesions in patients with metastatic PCa. As would be expected, PSMA-targeted PET provides more information on soft-tissue disease. There may be little additional value to imaging PCa patients with Na18F after a PSMA-targeted PET scan has already been performed.
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Bioelectrical Impedance Measurements for Assessment of Kidney Function in Critically Ill Patients.
de Jong, LAA, Otten-Helmers, AG, Spronk, PE, van Kan, HJM
Critical care medicine. 2019;(12):e984-e992
Abstract
OBJECTIVES To evaluate the use of multifrequency bioelectrical impedance analysis to predict creatinine/urea clearance based on 24 hours urine collection. A practical formula was developed, and its performance was compared with that of established formulas such as Cockcroft-Gault, Modification of Diet in Renal Disease, and Jelliffe's. DESIGN An open-label prospective observational cohort study. SETTING A 12-bed ICU at a nonuniversity major teaching hospital (Gelre ziekenhuizen Apeldoorn/Zutphen, The Netherlands). PATIENTS Adult critical care patients with an expected ICU length of stay at admission of at least 48 hours. INTERVENTIONS Each patient's body composition was assessed using a validated Quadscan 4000 analyzer (Bodystat, Isle of Man, British Isles). Twenty-four hours urine was collected, and laboratory variables in serum including creatinine, urea, and albumin were obtained at the beginning and end of the collection period. MEASUREMENTS AND MAIN RESULTS A total of 151 patients, stratified to an acute and nonacute ICU-group, were enrolled in the study over a 2-year period. A formula to predict creatinine/urea clearance based on 24 hours urine collection was developed using stepwise linear regression using a training data set of 75 patients. This formula was subsequently tested and compared with other relevant predictive equations using a validation data set of 76 patients. Serum creatinine values ranged from 40 to 446 µmol/L. With the predictive model based on estimated body cell mass and a "prediction marker" more than 71% of the observed variance in creatinine/urea clearance based on 24 hours urine collection could be explained. Predictive performance was superior to the other eight evaluated models (R = 0.39-0.55) and demonstrated to be constant over the whole range of creatinine/urea clearance based on 24 hours urine collection values. CONCLUSIONS Multifrequency bioelectrical impedance analysis measurements can be used to predict creatinine/urea clearance based on 24 hours urine collection with superior performance than currently established prediction models. This rapid, noninvasive method enables correction for influences of a patient's actual body composition and may prove valuable in daily clinical practice.
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3.
Intraindividual Comparison of 18F-PSMA-1007 and 18F-DCFPyL PET/CT in the Prospective Evaluation of Patients with Newly Diagnosed Prostate Carcinoma: A Pilot Study.
Giesel, FL, Will, L, Lawal, I, Lengana, T, Kratochwil, C, Vorster, M, Neels, O, Reyneke, F, Haberkon, U, Kopka, K, et al
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018;(7):1076-1080
Abstract
The introduction of 18F-labeled prostate-specific membrane antigen (PSMA)-targeted PET/CT tracers, first 18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) and more recently 18F-PSMA-1007 (((3S,10S,14S)-1-(4-(((S)-4-carboxy-2-((S)-4-carboxy-2-(6-18F-fluoronicotinamido)butanamido)butanamido)methyl)phenyl)-3-(naphthalen-2-ylmethyl)-1,4,12-trioxo-2,5,11,13-tetraazahexadecane-10,14,16-tricarboxylic acid)), have demonstrated promising results for the diagnostic workup of prostate cancer. This clinical study presents an intraindividual comparison to evaluate tracer-specific characteristics of 18F-DCFPyL versus 18F-PSMA-1007. Methods: Twelve prostate cancer patients, drug-naïve or before surgery, received similar activities of about 250 MBq of 18F-DCFPyL and 18F-PSMA-1007 48 h apart and were imaged 2 h after injection on the same PET/CT scanner using the same reconstruction algorithm. Normal-organ biodistribution and tumor uptake were quantified using SUVmaxResults: PSMA-positive lesions were detected in 12 of 12 prostate cancer patients. Both tracers, 18F-DCFPyL and 18F-PSMA-1007, detected the same lesions. No statistical significance could be observed when comparing the SUVmax of 18F-DCFPyL and 18F-PSMA-1007 for local tumor, lymph node metastases, and bone metastases. With regard to normal organs, 18F-DCFPyL had statistically significant higher uptake in kidneys, urinary bladder, and lacrimal gland. Vice versa, significantly higher uptake of 18F-PSMA-1007 in muscle, submandibular and sublingual gland, spleen, pancreas, liver, and gallbladder was observed. Conclusion: Excellent imaging quality was achieved with both 18F-DCFPyL and 18F-PSMA-1007, resulting in identical clinical findings for the evaluated routine situations. Nonurinary excretion of 18F-PSMA-1007 might present some advantage with regard to delineation of local recurrence or pelvic lymph node metastasis in selected patients; the lower hepatic background might favor 18F-DCFPyL in late stages, when rare cases of liver metastases can occur.
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Plaque pH in caries-free and caries-active young individuals before and after frequent rinses with sucrose and urea solution.
Hassan, H, Lingström, P, Carlén, A
Caries research. 2015;(1):18-25
Abstract
OBJECTIVE To examine pH in the approximal dental biofilm after acid and alkali formation from sucrose and urea, after an adaptation period to these substances, in caries-free (CF) and caries-active (CA) individuals. Saliva flow and buffer capacity, and aciduric bacteria in saliva and plaque were also examined. MATERIAL AND METHODS Twenty adolescents and young adults (15-21 years) with no caries (n = 10, D(m + i)MFS = 0) or ≥1 new manifest lesions/year (n = 10, DmMFS = 3.4 ± 1.8) participated. After plaque sampling, interproximal plaque pH was measured using the strip method before (baseline) and up to 30 min (final pH) after random distribution of a 1-min rinse with 10 ml of 10% sucrose or 0.25% urea. This procedure was repeated after a 1-week adaptation period of rinsing 5 times/day with 10 ml of the selected solution. After a 2-week washout period the second solution was similarly tested. Mutans streptococci, lactobacilli and pH 5.2-tolerant bacteria were analyzed by culturing. RESULTS In the CF group, acid adaptation resulted in lowering of baseline and final plaque pH values after a sugar challenge, and in increased numbers of bacteria growing at pH 5.2, which was increased also after alkali adaptation. In the CA group, the final pH was decreased after acid adaptation. No clear effects of alkali adaptation were seen in this group. CONCLUSION One-week daily rinses with sucrose and urea had the most pronounced effect on the CF group, resulting in increased plaque acidogenicity from the sugar rinses and increased number of acid-tolerant plaque bacteria from both rinses.
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Mapisal Versus Urea Cream as Prophylaxis for Capecitabine-Associated Hand-Foot Syndrome: A Randomized Phase III Trial of the AIO Quality of Life Working Group.
Hofheinz, RD, Gencer, D, Schulz, H, Stahl, M, Hegewisch-Becker, S, Loeffler, LM, Kronawitter, U, Bolz, G, Potenberg, J, Tauchert, F, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2015;(22):2444-9
Abstract
PURPOSE Hand-foot syndrome (HFS) is a frequently occurring adverse event associated with anticancer drugs. This study compares a newly introduced ointment containing several antioxidants and exhibiting high radical protection factor, which has been available on the German market since 2011, with urea cream for prevention of HFS in patients treated with capecitabine. PATIENTS AND METHODS Patients with GI tumors or breast cancer treated with capecitabine were included in this randomized phase III study. The primary end point was prevention of HFS of any grade within 6 weeks of treatment as indicated by a standardized patient diary. The study had 80% power to show a 20% reduction of the incidence of HFS with the new ointment. Secondary end points included time to development of HFS greater than grade 1, evaluation of capecitabine dose intensity, and quality of life analyses. RESULTS A total of 152 patients were evaluable. In total, 47 of 152 patients experienced HFS (30.9%), 39.5% with the new ointment and 22.4% in the urea arm (stratified odds ratio, 2.37; P = .02). Time to HFS greater than grade 1 was comparable, but time to any-grade HFS was significantly longer in the urea group (P = .03). Capecitabine dose intensity, time under study, and percentage of days with correct administration of study medication were identical, as were adverse events except for HFS. Skin-related quality of life was significantly worse in the group treated with the new ointment at the end of study treatment. CONCLUSION This trial demonstrated that 10% urea cream was superior to the new ointment at preventing HFS over the first 6 weeks of treatment with capecitabine.
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Use of a urea, arginine and carnosine cream versus a standard emollient glycerol cream for treatment of severe xerosis of the feet in patients with type 2 diabetes: a randomized, 8 month, assessor-blinded, controlled trial.
Federici, A, Federici, G, Milani, M
Current medical research and opinion. 2015;(6):1063-9
Abstract
BACKGROUND No long-term data are available regarding the effects of emollients in treating severe foot skin xerosis in patients with diabetes. STUDY AIM We evaluated the efficacy of 8 month urea, arginine and carnosine cream (UC) in comparison with a glycerin-based emollient cream (SEC) in type 2 patients with diabetes who had severe foot xerosis. SUBJECTS AND METHODS We assessed the effect of UC and SEC on skin hydration in a randomized, assessor-blinded study in 50 patients treated with UC (N = 25) or SEC (N = 25) for 32 weeks with a twice daily application. Primary outcomes were a 9 point Xerosis Assessment Scale (XAS) score and a 4 point Overall Cutaneous Score (OCS), evaluated at baseline and after 4, 12 and 32 weeks. Skin hydration and desquamation were also objectively evaluated by means of a bio-impedance skin analysis device (Hydr8 * ) at baseline and at week 32. RESULTS UC induced greater hydration than SEC (p = 0.001) with a 91% reduction at week 32 in XAS score vs. baseline. After 4 weeks, compared with the SEC treated group, the XAS score in the UC treated group was significantly lower. OCS was reduced by 27% from baseline to end of the study in the UC group, and increased by 8% in the SEC group (p = 0.02; between groups). At month 8, skin hydration and desquamation evaluated by the digital skin analysis system statistically improved in UC treated subjects in comparison with baseline and SEC group values. This study was not double-blind. In order to overcome this problem we performed an assessor-blinded evaluation of the primary endpoints and used an objective measurement tool for skin hydration and desquamation assessment. CONCLUSION Using a urea, arginine and carnosine cream for 8 months increases skin hydration and improves skin dryness in type 2 diabetic patients in comparison with a glycerol-based emollient cream, with a greater efficacy observed as early as 4 weeks into treatment.
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Finding the cause of acute kidney injury: which index of fractional excretion is better?
Gotfried, J, Wiesen, J, Raina, R, Nally, JV
Cleveland Clinic journal of medicine. 2012;(2):121-6
Abstract
The fractional excretion of urea (FEU) is a useful index for differentiating the main categories of causes of acute kidney injury, ie, prerenal causes and intrinsic causes. It may be used in preference to the more widely used fractional excretion of sodium (FENa) in situations in which the validity of the latter is limited, such as in patients taking a diuretic.
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Clinical evaluation of 35% urea in a water-lipid-based foam containing lactic acid for treatment of mild-to-moderate xerosis of the foot.
Grossman, AB
Journal of the American Podiatric Medical Association. 2011;(2):153-8
Abstract
BACKGROUND We evaluated 35% urea in a water-lipid-based foam delivery system containing lactic acid in participants with mild-to-moderate xerosis of the foot. METHODS This 4-week open-label study enrolled 12 participants with xerosis of the foot; six participants were diabetic and six were nondiabetic. Study medication was applied to the affected area twice daily. All adverse events were recorded. Disease severity was measured at baseline and at the end of treatment by Investigator's Global Assessment, and investigator's and participant's signs and symptoms scores. At 4 weeks, compliance and participant satisfaction were determined from participant diaries and a 16-item survey instrument, respectively. RESULTS Ten participants completed the study. No adverse reactions were noted with application of the foam. All of the participants who completed the study experienced an improvement in xerosis. The median Investigator's Global Assessment score decreased significantly from baseline to the end of treatment (P = .005). The investigator and participants observed significant improvement (P < .05) in redness, scaling, and cracking from baseline to the end of treatment. Compliance with the regimen was good, and participants expressed satisfaction with the product. CONCLUSIONS Thirty-five percent urea in a water-lipid-based foam delivery system containing lactic acid can be an appropriate treatment option for mild-to-moderate xerosis of the foot.
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Ammonia control in children with urea cycle disorders (UCDs); phase 2 comparison of sodium phenylbutyrate and glycerol phenylbutyrate.
Lichter-Konecki, U, Diaz, GA, Merritt, JL, Feigenbaum, A, Jomphe, C, Marier, JF, Beliveau, M, Mauney, J, Dickinson, K, Martinez, A, et al
Molecular genetics and metabolism. 2011;(4):323-9
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Abstract
UNLABELLED Twenty four hour ammonia profiles and correlates of drug effect were examined in a phase 2 comparison of sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB or HPN-100), an investigational drug being developed for urea cycle disorders (UCDs). STUDY DESIGN Protocol HPN-100-005 involved open label fixed-sequence switch-over from the prescribed NaPBA dose to a PBA-equimolar GPB dose with controlled diet. After 7 days on NaPBA or GPB, subjects underwent 24-hour blood sampling for ammonia and drug metabolite levels as well as measurement of 24-hour urinary phenyacetylglutamine (PAGN). Adverse events (AEs), safety labs and triplicate ECGs were monitored. RESULTS Eleven subjects (9 OTC, 1 ASS, 1 ASL) enrolled and completed the switch-over from NaPBA (mean dose=12.4 g/d or 322 mg/kg/d; range=198-476 mg/kg/d) to GPB (mean dose=10.8 mL or 0.284 mL/kg/d or 313 mg/kg/d; range=192-449 mg/kg/d). Possibly-related AEs were reported in 2 subjects on NaPBA and 4 subjects on GPB. All were mild, except for one moderate AE of vomiting on GPB related to an intercurrent illness. No clinically significant laboratory or ECG changes were observed. Ammonia was lowest after overnight fast, peaked postprandially in the afternoon to early evening and varied widely over 24h with occasional values >100 μmol/L without symptoms. Ammonia values were ~25% lower on GPB vs. NaPBA (p≥0.1 for ITT and p<0.05 for per protocol population). The upper 95% confidence interval for the difference between ammonia on GPB vs. NaPBA in the ITT population (95% CI 0.575, 1.061; p=0.102) was less than the predefined non-inferiority margin of 1.25 and less than 1.0 in the pre-defined per-protocol population (95% CI 0.516, 0.958; p<0.05). No statistically significant differences were observed in plasma phenylacetic acid and PAGN exposure during dosing with GPB vs. NaPBA, and the percentage of orally administered PBA excreted as PAGN (66% for GPB vs. 69% for NaPBA) was very similar. GPB and NaPBA dose correlated best with urinary-PAGN. CONCLUSIONS These findings suggest that GPB is at least equivalent to NaPBA in terms of ammonia control, has potential utility in pediatric UCD patients and that U-PAGN is a clinically useful biomarker for dose selection and monitoring.
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[Topically applied arginine hydrochloride. Effect on urea content of stratum corneum and skin hydration in atopic eczema and skin aging].
Nenoff, P, Donaubauer, K, Arndt, T, Haustein, UF
Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete. 2004;(1):58-64
Abstract
BACKGROUND AND OBJECTIVE Currently, there are no data on how the topical application of amino acids influences the complex moisture retaining system of the skin in vivo. PATIENTS/METHODS An open study was performed to investigate the effects of topical application of arginine hydrochloride on epidermal stratum corneum urea content, transepidermal water loss, skin hydration, and clinical status of patients with atopic dermatitis and dry elderly skin. RESULTS Treatment of patients with atopic dermatitis with 2.5% arginine hydrochloride ointment over 4 weeks showed a significant increase in urea in the stratum corneum as well as a continuous increase in skin moisture. CONCLUSIONS The urea deficit in the stratum corneum in atopic dermatitis and elderly skin was corrected not by applying the moisturizer urea itself but instead by using arginine - its precursor in the Krebs-Henseleit urea cycle. This topical treatment also improved the clinical symptoms of dry skin.