P0894OBESITY IMPAIRS THE ACUTE RESPONSE TO AN ORAL PHOSPHATE CHALLENGE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mandy Turner ◽  
Christine White ◽  
Patrick Norman ◽  
Corinne Babiolakis ◽  
Michael Adams ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Risk ◽  
Kidney Function ◽  
Area Under The Curve ◽  
Fractional Excretion ◽  
Low Risk ◽  
Normal Kidney ◽  
Phosphate Excretion ◽  
Fractional Excretion Of Phosphate ◽  
Age And Sex

Abstract Background and Aims T Obesity is an increasing health problem world-wide. People who are overweight or obese are at greater risk of developing chronic diseases including cardiovascular disease (CVD). Factors associated with dysregulated phosphate metabolism have been linked to the presence of vascular calcification in people with type 2 diabetes (T2D) with normal kidney function. Insulin resistance and abdominal obesity are associated with increased circulating levels of phosphaturic hormones including fibroblast growth factor 23 (FGF-23) and parathyroid hormone (PTH). Abnormalities in phosphate regulation may not be reflected in single circulating measurements of serum phosphate, but can be revealed by the acute circulating and mineral response to an oral challenge of phosphate. The aim of this study was to determine if obesity and insulin resistance impact the acute capacity to excrete an oral phosphate challenge. Method Community-dwelling people (N=78) free of T2D and symptomatic CVD (∼10 males and ∼10 females from each decade between 40 and 80 years) with normal kidney function were recruited from Kingston, Ontario, Canada. Following a 12-hour fast, participants consumed a 1250 mg phosphate drink (sodium phosphate) where blood and urine were collected at baseline, 1, 2 and 3 hours following the oral challenge. Participants with a high-risk metabolic profile characterized by an elevated waist-to-height ratio (WHtR) (> 0.58) were matched by age and sex to participants with a low risk WHtR (<0.5). Results The results reveal a significant impact of obesity on phosphate excretion in response to an oral phosphate challenge. There was an association between WHtR ratio and the level of iFGF-23 (R=-0.34 p<0.01) but not PTH. After adjustment for age and sex, WHtR ratio was inversely correlated with urinary phosphate excretion in response to the phosphate challenge (R=-0.29, p=0.02) and the change in fractional excretion of phosphate (r=-0.34, p=0.007). From the larger cohort, an age- and sex- matched subset was selected for 12 high risk and 12 low risk metabolic profiles with WHtR of 0.66±0.02 and 0.46±0.01, respectively. Kidney function was the same between the two groups (eGFR 92.3±13.1 versus 95.8±13.6 ml/min/1.73m2 respectively) but high risk participants had significantly higher homeostatic model assessment of insulin resistance (HOMA-IR) (1.61±0.81 versus 0.68±0.3, p<0.01). Participants with a high risk metabolic profile had a greater increase in serum phosphate from baseline (29% increase in the area under the curve, p=0.04) and a significantly blunted increase in the fractional excretion of phosphate in response to the oral phosphate challenge (35% reduction in area under the curve [AUC], p=0.03) compared to the matched low risk profile participants. Conclusion Overweight/obese individuals demonstrate impaired response to an oral phosphate challenge, whereby phosphate excretion was impaired and there was increased exposure to new circulating phosphate. An impaired acute phosphate response may contribute to the initiation or propagation of vascular calcification. Dysregulated phosphate homeostasis may be an under-recognized cardiovascular risk factor in obese people that could be modified by diet and weight loss. Whether insulin enhances renal phosphate reabsorption requires further study.

scholarly journals A Prediction Model for Metachronous Peritoneal Carcinomatosis in Patients with Stage T4 Colon Cancer after Curative Resection

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2808
Author(s):  
Tzong-Yun Tsai ◽  
Jeng-Fu You ◽  
Yu-Jen Hsu ◽  
Jing-Rong Jhuang ◽  
Yih-Jong Chern ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Prediction Model ◽  
Prediction Error ◽  
Area Under The Curve ◽  
Low Risk ◽  
Brier Score ◽  
Individual Risk ◽  
T4 Colon Cancer ◽  
Testing Set

(1) Background: The aim of this study was to develop a prediction model for assessing individual mPC risk in patients with pT4 colon cancer. Methods: A total of 2003 patients with pT4 colon cancer undergoing R0 resection were categorized into the training or testing set. Based on the training set, 2044 Cox prediction models were developed. Next, models with the maximal C-index and minimal prediction error were selected. The final model was then validated based on the testing set using a time-dependent area under the curve and Brier score, and a scoring system was developed. Patients were stratified into the high- or low-risk group by their risk score, with the cut-off points determined by a classification and regression tree (CART). (2) Results: The five candidate predictors were tumor location, preoperative carcinoembryonic antigen value, histologic type, T stage and nodal stage. Based on the CART, patients were categorized into the low-risk or high-risk groups. The model has high predictive accuracy (prediction error ≤5%) and good discrimination ability (area under the curve >0.7). (3) Conclusions: The prediction model quantifies individual risk and is feasible for selecting patients with pT4 colon cancer who are at high risk of developing mPC.

scholarly journals Very similar cardiometabolic profile in the moderate and high cardiovascular risk classes: a population-based study

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Chlabicz ◽  
J Jamolkowski ◽  
W Laguna ◽  
P Sowa ◽  
M Paniczko ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
High Risk ◽  
Population Based ◽  
Low Risk ◽  
Public Institution ◽  
Population Based Study ◽  
The Metabolic Syndrome ◽  
Cardiometabolic Profile

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Bialystok, Poland Background Cardiovascular disease (CVD) is a major, worldwide problem and remain the dominant cause of premature mortality in the word. Simultaneously the metabolic syndrome is a growing problem. The aim of this study was to investigate the cardiometabolic profile among cardiovascular risk classes, and to estimate CV risk using various calculators. Methods The longitudinal, population-based study, was conducted in 2017-2020. A total of 931 individuals aged 20-79 were included. Anthropometric and biochemical profiles were measured according to a standardized protocols. The study population was divided into CV risk classes according to the latest recommendation. Comparisons variables between subgroups were conducted using Dwass-Steele-Critchlow-Fligner test. To estimate CV risk were used: the  Systematic Coronary Risk Estimation system, Framingham Risk Score and LIFEtime-perspective model for individualizing CardioVascular Disease prevention strategies in apparently healthy people (LIFE-CVD). Results The mean age was 49.1± 15.5 years, 43.2% were male. Percentages of low-risk, moderate-risk, high-risk and very-high CV risk were 46.1%, 22.8%, 13.5%, 17.6%, respectively. Most of the analyzed anthropometric, body composition and laboratory parameters did not differ between the moderate and high CV risk participants, whereas the low risk group differed significantly. In the moderate and high-risk groups, abdominal distribution of adipose tissue dominated with significantly elevated parameters of insulin resistance. Interestingly, estimating lifetime risk of myocardial infarction, stroke or CV death using LIFE-CVD calculator yielded similar results in moderate and high CV risk classes. Conclusion The participants belonging to moderate and high CV risk classes have a very similar unfavorable cardiometabolic profile which may result in the similar lifetime CV risk. This may imply the need for more aggressive pharmacological and non-pharmacological management of CV risk factors in the moderate CV risk population. It would be advisable to consider combining the moderate and high risk classes into one high CV risk class, or it may be worth adding one of the parameters of abdominal fat distribution to the CV risk calculators as an expression of increased insulin resistance. Abstract Figure 1.

scholarly journals Adiposity indices in the prediction of insulin resistance in prepubertal Colombian children

2012 ◽  
Vol 16 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Noel T Mueller ◽  
Mark A Pereira ◽  
Adriana Buitrago-Lopez ◽  
Diana C Rodríguez ◽  
Alvaro E Duran ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Waist Circumference ◽  
Area Under The Curve ◽  
Skinfold Thickness ◽  
Model Assessment ◽  
Height Ratio ◽  
Prepubertal Children ◽  
Stepwise Selection ◽  
Waist To Height Ratio ◽  
Age And Sex

AbstractObjectiveTo compare BMI with abdominal skinfold thickness (ASF), waist circumference and waist-to-height ratio in the prediction of insulin resistance (IR) in prepubertal Colombian children.DesignWe calculated age- and sex-specific Z-scores for BMI, ASF, waist circumference, waist-to-height ratio and three other skinfold-thickness sites. Logistic regression with stepwise selection (P = 0·80 for entry and P = 0·05 for retention) was performed to identify predictors of IR and extreme IR, which were determined by age- and sex-specific Z-scores to identify the ≥ 90th and ≥ 95th percentile of homeostasis model assessment (HOMAIR), respectively. We used receiver operating characteristic curves to compare the area under the curve between models.SettingBucaramanga, Colombia.SubjectsChildren (n 1261) aged 6–10 years in Tanner stage 1 from a population-based study.ResultsA total of 127 children (seventy girls and fifty-seven boys) were classified with IR, including sixty-three children (thirty-three girls and thirty boys) classified with extreme IR. Only ASF and BMI Z-scores were retained as predictors of IR by stepwise selection. Adding ASF Z-score to BMI Z-score improved the area under the curve from 0·794 (95 % CI 0·752, 0·837) to 0·811 (95 % CI 0·770, 0·851; P for contrast = 0·01). In predicting extreme IR, the addition of ASF Z-score to BMI Z-score improved the area under the curve from 0·837 (95 % CI 0·790, 0·884) to 0·864 (95 % CI 0·823, 0·905; P for contrast = 0·01).ConclusionsASF Z-score predicted IR independent of BMI Z-score in our population of prepubertal children. ASF and BMI Z-scores together improved IR risk stratification compared with BMI Z-score alone, opening new perspectives in the prediction of cardiometabolic risk in prepubertal children.

scholarly journals Development and Validation of Two Self-Reported Tools for Insulin Resistance and Hypertension Risk Assessment in A European Cohort: The Feel4Diabetes-Study

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 960
Author(s):  
Spyridon Kanellakis ◽  
Christina Mavrogianni ◽  
Kalliopi Karatzi ◽  
Jaana Lindstrom ◽  
Greet Cardon ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Risk Assessment ◽  
High Risk ◽  
Sensitivity And Specificity ◽  
Low Cost ◽  
Area Under The Curve ◽  
Assessment Tools ◽  
Screening Tools ◽  
Model Assessment ◽  
Sugary Drinks

Early identification of type 2 diabetes mellitus (T2DM) and hypertension (HTN) risk may improve prevention and promote public health. Implementation of self-reported scores for risk assessment provides an alternative cost-effective tool. The study aimed to develop and validate two easy-to-apply screening tools identifying high-risk individuals for insulin resistance (IR) and HTN in a European cohort. Sociodemographic, lifestyle, anthropometric and clinical data obtained from 1581 and 1350 adults (baseline data from the Feel4Diabetes-study) were used for the European IR and the European HTN risk assessment index respectively. Body mass index, waist circumference, sex, age, breakfast consumption, alcohol, legumes and sugary drinks intake, physical activity and sedentary behavior were significantly correlated with Homeostatic Model Assessment of IR (HOMA-IR) and/or HTN and incorporated in the two models. For the IR index, the Area Under the Curve (AUC), sensitivity and specificity for identifying individuals above the 75th and 95th of HOMA-IR percentiles were 0.768 (95%CI: 0.721–0.815), 0.720 and 0.691 and 0.828 (95%CI: 0.766–0.890), 0.696 and 0.778 respectively. For the HTN index, the AUC, sensitivity and specificity were 0.778 (95%CI: 0.680–0.876), 0.667 and 0.797. The developed risk assessment tools are easy-to-apply, valid, and low-cost, identifying European adults at high risk for developing T2DM or having HTN.

Effect of acute hypoxia on phosphate excretion in rats

1994 ◽  
Vol 266 (2) ◽  
pp. R578-R583
Author(s):  
Y. Mimura ◽  
F. G. Knox
Keyword(s):  
Acute Hypoxia ◽  
Fractional Excretion ◽  
Respiratory Alkalosis ◽  
Renal Handling ◽  
Arterial Pco2 ◽  
Phosphate Excretion ◽  
Fractional Excretion Of Phosphate ◽  
Spontaneously Breathing ◽  
Arterial Po2 ◽  
Hypoxic Group

This study evaluated the effect of acute hypoxia on renal handling of phosphate in rats in the presence and absence of parathyroid hormone (PTH). Hypoxia causes respiratory alkalosis in spontaneously breathing humans and animals. Respiratory alkalosis has been reported to induce a blunted phosphaturic response to PTH. In this study, to avoid the confounding effect of hypocapnia accompanying the hypoxia on phosphate excretion, the rats were ventilated mechanically, and arterial PCO2 levels were controlled. Rats were divided into two main groups depending on the arterial PO2 levels: a hypoxic group (n = 16) and a normoxic group (n = 18). Hypoxia was produced by ventilating with 10% oxygen, and hypocapnia was produced by hyperventilation. In response to PTH, the hypoxic rats without hypocapnia showed a greater increase in fractional excretion of phosphate (FEPi; 37.7 +/- 2.6%, mean +/- SE) compared with normoxic rats (27.4 +/- 2.5%, P < 0.02). During hypocapnia, there was no difference in FEPi between hypoxic and normoxic groups (21.2 +/- 1.5 and 19.5 +/- 1.2%, respectively), and both groups showed a significantly blunted phosphaturic response to PTH compared with normocapnia (P < 0.05 and P < 0.01, respectively). Urinary adenosine 3',5'-cyclic monophosphate (cAMP) increased similarly after PTH infusion between each group. To test whether the phosphaturic effect of PTH in hypoxia and the blunted phosphaturic effect of PTH in hypocapnia are due to steps beyond the generation of cAMP, the phosphaturic response to cAMP infusion was evaluated in 1) hypoxic and normocapnic rats (n = 6), 2) normoxic and normocapnic (control) rats (n = 6), and 3) normoxic and hypocapnic rats (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Phosphate excretion in uremic rats: effects of parathyroidectomy and phosphate restriction

1985 ◽  
Vol 248 (2) ◽  
pp. F175-F182
Author(s):  
E. Kraus ◽  
G. Briefel ◽  
L. Cheng ◽  
B. Sacktor ◽  
D. Spector
Keyword(s):  
Fractional Excretion ◽  
Tubular Reabsorption ◽  
Sprague Dawley ◽  
Dietary Regimen ◽  
Phosphate Excretion ◽  
Sprague Dawley Rats ◽  
Dietary Phosphate ◽  
Phosphate Loading ◽  
Fractional Excretion Of Phosphate ◽  
Renal Phosphate Excretion

As progressive renal failure develops, phosphate excretion per functioning nephron increases, thus preserving homeostasis. To test whether dietary phosphate supply might contribute to the regulation of renal phosphate excretion in the uremic setting, groups of male Sprague-Dawley rats that were either parathyroidectomized (PTX) or sham PTX (S-PTX) and either five-sixths nephrectomized (Nx) or sham Nx (S-Nx) were studied following a 4-wk dietary regimen consisting of 0.1 or 0.7% phosphate. For Nx rats fed the 0.7% phosphate diet the fractional excretion of phosphate (FEPi) was enhanced (47 +/- 6 vs. 21 +/- 3%) and the maximum tubular reabsorption of phosphate per milliliter GFR (TmPi/GFR) was suppressed (1.65 +/- 0.19 vs. 2.33 +/- 0.19 mumol/ml). FEPi was unchanged by PTX in these Nx animals (42 +/- 6 vs. 47 +/- 6%). TmPi/GFR remained suppressed in PTX, NX animals when compared with S-Nx, PTX controls (3.38 +/- 0.33 vs. 5.07 +/- 0.41 mumol/ml). For rats fed the 0.1% phosphate diet Nx did not affect TmPi/GFR in either S-PTX (5.40 +/- 0.43 vs. 4.97 +/- 0.34 mumol/ml) or PTX (7.03 +/- 0.23 vs. 6.98 +/- 0.21 mumol/ml) animals. For both S-Nx and Nx animals the effects of PTX and dietary phosphate restriction on TmPi/GFR were independent and additive. In all groups of animals, tubular reabsorption of phosphate per milliliter GFR (TRPi/GFR) dropped acutely with continued infusion of phosphate once TmPi/GFR was achieved. Thus, a resetting of TRPi/GFR occurs among Nx rats in response to both chronic dietary phosphate deprivation and acute intravenous phosphate loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence and Prevalence of Patients with Myelodysplastic Syndromes (MDS) in Düsseldorf 1996-2005.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1774-1774 ◽  
Author(s):  
Judith Neukirchen ◽  
W. Marieke Schoonen ◽  
Carlo Aul ◽  
Rainer Haas ◽  
Norbert Gattermann ◽  
...  
Keyword(s):  
High Risk ◽  
Myelodysplastic Syndromes ◽  
Research Funding ◽  
Population Based ◽  
Low Risk ◽  
High Risk Disease ◽  
Population Counts ◽  
Incident Cases ◽  
The Town ◽  
Age And Sex

Abstract Abstract 1774 Poster Board I-800 Background Population-based data on myelodysplastic syndromes (MDS) are scarce. Since its inception in 1982, the Düsseldorf MDS Registry has captured 3598 patients with MDS, of whom 21 % live in the town district of Düsseldorf. Between 1996-2005 we are confident that all MDS patients residing in the town district of Düsseldorf were entered and followed in the registry through regular follow-ups. As yearly age- and sex-specific population counts are also available for Düsseldorf, the Registry provides a unique opportunity to estimate MDS disease frequency. Here we aim to quantify the incidence and prevalence of MDS disease subtypes. Methods Patients were identified from the MDS Registry. Age- and sex-specific yearly population counts were obtained from the Statistical Office of North-Rhine Westphalia. The number of residents in Düsseldorf minimally increased during the study period from 1996 to 2005 (mean: 571,000 residents). The number of patients with a first-time MDS diagnosis in a given calendar year (incident cases) was divided by the total Düsseldorf population in that year to estimate incidence. Prevalence was estimated by dividing the number of existing plus incident MDS patients in a given year by the total population of Düsseldorf that year. Incidence (per 100,000 person-years (PY) and prevalence per 100,000 persons are presented with corresponding 95% confidence intervals (CI) calculated using the delta and Wilson methods, respectively. Low-risk MDS was defined as WHO subtypes RA, RCMD or MDS with del(5q). High-risk included subtypes RAEB-I and RAEB-II. Results 344 MDS patients were included in our analyses (279 incident patients). Incidence and prevalence of low-risk MDS was 2.87 (95%CI 2.46–3.35) per 100,000PY and 12.4 (95%CI 11.5–13.4) per 100,000 persons, respectively, with no difference between men and women (Table). High-risk disease was less common. The incidence of high-risk disease in men appeared to be higher (1.22 (95%CI 0.87–1.72) per 100,000PY) than in women (0.63 (95%CI 0.40–0.99) per 100,000PY). Prevalence of high-risk disease among men was statistically significantly higher in men compared to women (2.93 (95%CI 2.35 – 3.65) per 100,000 persons) and 1.56 (95%CI 1.17 – 2.08) per 100,000 persons), respectively (Table). Conclusion In this population-based study we found that MDS more common in men than in women. The majority of MDS cases had low-risk disease. Incidence and prevalence of high risk disease (but not low risk) is higher in men compared to women. Financial disclosures: This study was supported by Amgen Inc. Disclosures Neukirchen: Amgen Inc.: Research Funding. Schoonen:Amgen Inc.: Research Funding. Aul:Amgen Inc.: Research Funding. Haas:Amgen Inc.: Research Funding. Gattermann:Amgen Inc., Celgene, Novartis: Honoraria, Research Funding. Germing:Amgen Inc., Celgene, Novartis: Honoraria, Research Funding.

scholarly journals Utility of radiomics for predicting patient survival in hepatocellular carcinoma with portal vein tumor thrombosis treated with stereotactic body radiotherapy

2020 ◽  
Author(s):  
Kui Wu ◽  
Yongjie Shui ◽  
Wenzheng Sun ◽  
Sheng Lin ◽  
Haowen Pang
Keyword(s):  
High Risk ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Patient Survival ◽  
Risk Group ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Risk Groups ◽  
High Risk Group ◽  
Low Risk

Abstract Objective This study aimed to develop and validate the combination of radiomic features and clinical characteristics that can predict patient survival in HCC with PVTT treated with SBRT. Materials and Methods The prediction model was developed in a primary cohort of 70 patients with HCC and PVTT treated with SBRT, using data acquired between December 2015 and June 2017. The radiomic features were extracted from computed tomography (CT) scans. A least absolute shrinkage and selection operator regression model was used to build the radiomic feature. Multivariate Cox-regression hazard models were created for analyzing survival outcomes and the radiomic features and clinical characteristics were presented with a nomogram. The area under the curve (AUC) of the receiver operating characteristic curve was used to evaluate the model. Participants were divided into a high-risk group and a low-risk group based on the radiomic features. Results A total of seven radiomic features and five clinical characteristics were extracted for survival analysis. A combination of the radiomic features and clinical characteristics resulted in better performance for the estimation of overall survival (OS) [AUC = 0.859 (CI: 0.770–0.948)] than that with clinical characteristics alone [AUC = 0.761 (CI: 0.641–0.881)]. These patients were divided into high-risk and low-risk groups according to the radiomic features. Conclusion This study demonstrated that a nomogram of combined radiomic features and clinical characteristics can be conveniently used to facilitate individualized preoperative prediction of OS in patients with HCC with PVTT before SBRT.

scholarly journals 3,023 Mayo Clinic Patients with Myeloproliferative Neoplasms: Risk-Stratified Comparison of Survival and Outcomes Data Among Disease Subgroups

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3035-3035
Author(s):  
Natasha Szuber ◽  
Mythri Mudireddy ◽  
Maura Nicolosi ◽  
Domenico Penna ◽  
Rangit Vallapureddy ◽  
...  
Keyword(s):  
High Risk ◽  
Life Expectancy ◽  
Risk Stratification ◽  
Survival Data ◽  
Mayo Clinic ◽  
Large Scale ◽  
Myeloproliferative Neoplasms ◽  
Low Risk ◽  
Age And Sex

Abstract Background: While several population-based studies have reported on adverse outcomes and life expectancy in myeloproliferative neoplasms (MPN) (JCO. 2015;33:2288; AJH. 1999;61:10; Leukemia. 2013;27:1874; JCO. 2012;30:2995), large-scale studies reporting mature data have been rare and important questions remain unanswered. The current study documents the Mayo Clinic (MC) decades-long experience with over 3,000 consecutive MPN patients including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) with the majority of patients followed until death. Herein, we provide mature, and importantly, risk-stratified survival data and disease complication estimates. Methods: Study patients were recruited from MC, Rochester, MN, USA between 10/27/1967 and 12/29/2017. All MPN diagnoses and documentation of fibrotic/leukemic transformations were in accordance with the 2016 World Health Organization criteria (Blood. 2016;127:2391). Clinical and laboratory data were abstracted from medical records. Risk-stratification used conventional risk models considering age, leukocytes, and venous thrombosis for PV (Leukemia. 2013;27:1874), international prognostic score for ET (Blood. 2012;120:1197), and dynamic international prognostic scoring system for PMF (Blood. 2010;115:1703). Statistical analyses were based on parameters obtained at the time of referral to MC which, in the majority of cases, coincided with or was within 1 year of diagnosis. All patients were followed from diagnosis until death or date of last follow-up/contact. Recipients of allogeneic stem cell transplants were censored at the time of transplant. Standard statistical methods and time-to-event curves prepared using the Kaplan-Meier method were used to compare MPN subgroups. Survival data for low-risk ET/PV were compared with age- and sex-matched controls from Olmstead County, MN, USA. JMP® Pro 13.0.0 software (SAS Institute, Cary, NC, USA) was used for all analyses. Results: 3,023 consecutive patients (median age 62 years, range 18-96; 51% males) were considered, including 89% diagnosed within the year: 665 PV, 1076 ET and 1282 PMF. Conventional risk stratification in 2925 evaluable patients revealed low, intermediate, and high-risk status in 26%, 29%, and 45% of PV and 30%, 42%, and 28% of ET patients, respectively, while PMF cases were attributed low (14%), intermediate-1 (38%) -2 (40%) and high (8%) risk (Table 1). After a median follow-up of 8.2 years for PV (range 0-39), 9.9 for ET (range 0-47), and 3.2 for PMF (range 0-31), 1631 (54%) deaths, 183 (6%) leukemic transformations, 244 (14%) fibrotic progressions, and 516 (17%) thrombotic events were recorded (Table 1). Median overall survival (OS) was 18 years for ET, 15 for PV and 4.4 for PMF (p<0.05 for all inter-group comparisons) (Figure 1A). Leukemia-free survival was similar for ET and PV (p=0.22) and significantly worse for PMF (p<0.001) (Figure 1B). PV, compared to ET, was associated with higher risk of fibrotic progression (p<0.001) (Figure 1C). Thrombosis risk after diagnosis was highest in PV and lowest in PMF (p=0.002 for PV vs ET; 0.56 for ET vs PMF; and 0.001 for PV vs PMF) (Figure 1D). Following risk stratification, median OS in low-risk ET (28 years) and low-risk PV (27 years) were superimposed (p=0.89) (Figure 2). Similarly, intermediate or high-risk PV and ET patients had comparable OS within each risk strata (p=0.23 and 0.11, respectively). Low-risk PMF survival was analogous to that of intermediate-risk PV (p=0.06). All other risk-stratified categories disclosed significantly different inter- and intra-group survival patterns (p<0.001) (Figure 2). Despite their categorization as favorable-risk disease, both low-risk ET and low-risk PV displayed excess mortality relative to age- and sex-matched controls with median survival of 26.7 and 28.1 years respectively, compared to the expected 37.5 and 39.2 years (p<0.001) (Figure 3). Conclusions: The current study provides large-scale and uniquely mature survival and outcomes data in MPN and highlights MPN subgroup risk categorization as cardinal in appraising disease natural history. Interestingly, OS was only marginally better in ET, compared to PV, while the latter clearly displayed a higher risk of thrombosis and fibrotic progression. Moreover, data disclosed shortened life expectancy relative to matched controls even in MPN with favorable risk attribution. Disclosures Busque: BMS: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Paladin: Consultancy.

Developmental changes in the phosphaturic response to parathyroid hormone in the rat

1985 ◽  
Vol 249 (2) ◽  
pp. F251-F255 ◽  
Author(s):  
S. K. Webster ◽  
A. Haramati
Keyword(s):  
Parathyroid Hormone ◽  
Fractional Excretion ◽  
Developmental Changes ◽  
High Dose ◽  
Kidney Weight ◽  
Phosphate Excretion ◽  
Immature Rats ◽  
Glomerular Filtrate ◽  
Old Rats ◽  
Fractional Excretion Of Phosphate

The need for young, immature rats to maintain positive phosphate balance for growth is well recognized. However, whether this process is associated with a resistance to the phosphaturic effect of parathyroid hormone (PTH) is not clear. In these experiments we examined the effect of PTH on urinary phosphate and cAMP excretion in rats at 3, 6, 12, and 20 wk of age. Clearance experiments were performed in acutely thyroparathyroidectomized (TPTX) rats fed a normal phosphate diet (0.86%). Basal fractional excretion of phosphate (FEPi) was low in all TPTX rats (less than 1%). The phosphaturic response to a high dose of PTH (1 U X kg-1 X min-1) increased with development (from 4 to 29%). The responses to increasing doses of PTH demonstrated a decrease in sensitivity to PTH in 6- compared with 20-wk-old rats. Urinary cAMP excretion (either per milliliter glomerular filtrate or per gram kidney weight) following PTH was not different among 6-, 12-, and 20-wk-old rats, thus demonstrating a dissociation between the increase in phosphate excretion and cAMP excretion. These results indicate that the phosphaturic response to PTH is blunted in immature, acutely TPTX rats and that the phosphaturia increases progressively with development.

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