Role of endoscopic ultrasonography in the diagnostic work-up of idiopathic acute pancreatitis (PICUS): study protocol for a nationwide prospective cohort study

Introduction Idiopathic acute pancreatitis (IAP) remains a dilemma for physicians as it is uncertain whether patients with IAP may actually have an occult aetiology. It is unclear to what extent additional diagnostic modalities such as endoscopic ultrasonography (EUS) are warranted after a first episode of IAP in order to uncover this aetiology. Failure to timely determine treatable aetiologies delays appropriate treatment and might subsequently cause recurrence of acute pancreatitis. Therefore, the aim of the Pancreatitis of Idiopathic origin: Clinical added value of endoscopic UltraSonography (PICUS) Study is to determine the value of routine EUS in determining the aetiology of pancreatitis in patients with a first episode of IAP. Methods and analysis PICUS is designed as a multicentre prospective cohort study of 106 patients with a first episode of IAP after complete standard diagnostic work-up, in whom a diagnostic EUS will be performed. Standard diagnostic work-up will include a complete personal and family history, laboratory tests including serum alanine aminotransferase, calcium and triglyceride levels and imaging by transabdominal ultrasound, magnetic resonance imaging or magnetic resonance cholangiopancreaticography after clinical recovery from the acute pancreatitis episode. The primary outcome measure is detection of aetiology by EUS. Secondary outcome measures include pancreatitis recurrence rate, severity of recurrent pancreatitis, readmission, additional interventions, complications, length of hospital stay, quality of life, mortality and costs, during a follow-up period of 12 months. Ethics and dissemination PICUS is conducted according to the Declaration of Helsinki and Guideline for Good Clinical Practice. Five medical ethics review committees assessed PICUS (Medical Ethics Review Committee of Academic Medical Center, University Medical Center Utrecht, Radboud University Medical Center, Erasmus Medical Center and Maastricht University Medical Center). The results will be submitted for publication in an international peer-reviewed journal.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

The reliability of continuous measurement of mixed venous oxygen saturation during exercise in patients with chronic heart failure

Continuous assessment of mixed venous oxygen saturation (cSvO2) during exercise using a fiber optic pulmonary artery catheter can provide valuable information on the physiological determinants of the exercise capacity in patients with chronic heart failure (CHF). Since its accuracy is not well established during exercise, this study evaluated the reliability of a fiber optic pulmonary artery catheter for measuring SvO2 during exercise in CHF patients. Ten patients with stable CHF performed steady-state exercise tests at 30 and 80% of the ventilatory threshold and consequently a symptom-limited incremental exercise test. During the tests, SvO2 was monitored continuously using a fiber optic pulmonary artery catheter (CCOmbo, Edwards Lifesciences, Irvine, CA, USA) and by oximetric analysis of mixed venous blood samples obtained at rest (n = 26), steady state (n = 17) and peak exercise (n = 8). There was a significant correlation between oximetrically determined SvO2 and cSvO2 values (r = 0.97). The bias between both methods was 0.6% with limits of agreement from -8 to 9%. The limits of agreement for SvO2 values 30% (n = 35) (from -10 to 12% and from -7 to 8%, respectively). In conclusion, continuous measurement of SvO2 during exercise using a fiber optic pulmonary catheter is reliable in patients with CHF, with somewhat less accurate measurements of SvO2 below 30%

Are oxygen uptake kinetics in chronic heart failure limited by oxygen delivery or oxygen utilization?

Background: The delay in O2 uptake kinetics during and after submaximal physical activity (O2 onset and recovery kinetics, respectively) correlates well with the functional capacity of patients with chronic heart failure (CHF). This study examined the physiological background of this delay in moderately impaired CHF patients by comparing kinetics of cardiac output (Q?) and O2 uptake (V?O2 ). Methods: Fourteen stable CHF patients (New York Heart Association class II-III) and 8 healthy subjects, matched for age and body mass index, were included. All subjects performed a submaximal constant-load exercise test to assess O2 uptake kinetics. Furthermore, in 10 CHF patients Q? was measured by a radial artery pulse contour analysis method, which enabled the simultaneous modelling of exercise-related kinetics of Q? and V?O2 . Results: Both O2 onset and recovery kinetics were delayed in the patient group. There were no significant differences between the time constants of Q? and V?O2 during exercise-onset (62 -Ý 25- s versus 59 -Ý 28- s, p = 0.51) or recovery (61 -Ý 25- s versus 57 -Ý 20- s, p = 0.38) in the patient group, indicating that O2 delivery was not in excess of the metabolic demands in these patients. Conclusion: The delay in O2 onset and recovery kinetics in moderately impaired CHF patients is suggested to be due to limitations in O2 delivery. Therefore, strategies aimed at improving exercise performance of these patients should focus more on improvements of O2 delivery than on O2 utilization. -© 2008 Elsevier Ireland Ltd. All rights reserve

Are oxygen uptake kinetics in chronic heart failure limited by oxygen delivery or oxygen utilization?

Background: The delay in O2 uptake kinetics during and after submaximal physical activity (O2 onset and recovery kinetics, respectively) correlates well with the functional capacity of patients with chronic heart failure (CHF). This study examined the physiological background of this delay in moderately impaired CHF patients by comparing kinetics of cardiac output (Q?) and O2 uptake (V?O2 ). Methods: Fourteen stable CHF patients (New York Heart Association class II-III) and 8 healthy subjects, matched for age and body mass index, were included. All subjects performed a submaximal constant-load exercise test to assess O2 uptake kinetics. Furthermore, in 10 CHF patients Q? was measured by a radial artery pulse contour analysis method, which enabled the simultaneous modelling of exercise-related kinetics of Q? and V?O2 . Results: Both O2 onset and recovery kinetics were delayed in the patient group. There were no significant differences between the time constants of Q? and V?O2 during exercise-onset (62 -Ý 25- s versus 59 -Ý 28- s, p = 0.51) or recovery (61 -Ý 25- s versus 57 -Ý 20- s, p = 0.38) in the patient group, indicating that O2 delivery was not in excess of the metabolic demands in these patients. Conclusion: The delay in O2 onset and recovery kinetics in moderately impaired CHF patients is suggested to be due to limitations in O2 delivery. Therefore, strategies aimed at improving exercise performance of these patients should focus more on improvements of O2 delivery than on O2 utilization. -© 2008 Elsevier Ireland Ltd. All rights reserve

Skeletal muscle metabolic recovery following submaximal exercise in chronic heart failure is limited more by O2 delivery than O2 utilization

CHF (chronic heart failure) is associated with a prolonged recovery of skeletal muscle energy stores following submaximal exercise, limiting the ability to perform repetitive daily activities. However, the pathophysiological background of this impairment is not well established. The aim of the present study was to investigate whether muscle metabolic recovery following submaximal exercise in patients with CHF is limited by O2 delivery or O2 utilization. A total of 13 stable CHF patients (New York Heart Association classes II-III) and eight healthy subjects, matched for age and BMI (body mass index), were included. All subjects performed repetitive submaximal dynamic single leg extensions in the supine position. Post-exercise PCr (phosphocreatine) resynthesis was assessed by 31P-MRS (magnetic resonance spectroscopy). NIRS (near-IR spectroscopy) was applied simultaneously, using the rate of decrease in HHb (deoxygenated haemoglobin) as an index of post-exercise muscle re-oxygenation. As expected, PCr recovery was slower in CHF patients than in control subjects (time constant, 47 ± 10 compared with 35 ± 12 s respectively; P=0.04). HHb recovery kinetics were also prolonged in CHF patients (mean response time, 74±41 compared with 44±17 s respectively; P=0.04). In the patient group, HHb recovery kinetics were slower than PCr recovery kinetics (P=0.02), whereas no difference existed in the control group (P=0.32). In conclusion, prolonged metabolic recovery in CHF patients is associated with an even slower muscle tissue re-oxygenation, indicating a lower O2 delivery relative to metabolic demands. Therefore we postulate that the impaired ability to perform repetitive daily activities in these patients depends more on a reduced muscle blood flow than on limitations in O2 utilization. © The Authors Journal compilation © 2010 Biochemical Society

Skeletal muscle metabolic recovery following submaximal exercise in chronic heart failure is limited more by O2 delivery than O2 utilization

CHF (chronic heart failure) is associated with a prolonged recovery of skeletal muscle energy stores following submaximal exercise, limiting the ability to perform repetitive daily activities. However, the pathophysiological background of this impairment is not well established. The aim of the present study was to investigate whether muscle metabolic recovery following submaximal exercise in patients with CHF is limited by O2 delivery or O2 utilization. A total of 13 stable CHF patients (New York Heart Association classes II-III) and eight healthy subjects, matched for age and BMI (body mass index), were included. All subjects performed repetitive submaximal dynamic single leg extensions in the supine position. Post-exercise PCr (phosphocreatine) resynthesis was assessed by 31P-MRS (magnetic resonance spectroscopy). NIRS (near-IR spectroscopy) was applied simultaneously, using the rate of decrease in HHb (deoxygenated haemoglobin) as an index of post-exercise muscle re-oxygenation. As expected, PCr recovery was slower in CHF patients than in control subjects (time constant, 47 ± 10 compared with 35 ± 12 s respectively; P=0.04). HHb recovery kinetics were also prolonged in CHF patients (mean response time, 74±41 compared with 44±17 s respectively; P=0.04). In the patient group, HHb recovery kinetics were slower than PCr recovery kinetics (P=0.02), whereas no difference existed in the control group (P=0.32). In conclusion, prolonged metabolic recovery in CHF patients is associated with an even slower muscle tissue re-oxygenation, indicating a lower O2 delivery relative to metabolic demands. Therefore we postulate that the impaired ability to perform repetitive daily activities in these patients depends more on a reduced muscle blood flow than on limitations in O2 utilization. © The Authors Journal compilation © 2010 Biochemical Society

Physical activity and sedentary behavior show distinct associations with tissue-specific insulin sensitivity in adults with overweight

AimThe aim of this study is to investigate associations between the physical activity (PA) spectrum (sedentary behavior to exercise) and tissue-specific insulin resistance (IR). MethodsWe included 219 participants for analysis (median [IQR]: 61 [55; 67] years, BMI 29.6 [26.9; 32.0] kg/m(2); 60% female) with predominant muscle or liver IR, as determined using a 7-point oral glucose tolerance test (OGTT). PA and sedentary behavior were measured objectively (ActivPAL) across 7 days. Context-specific PA was assessed with the Baecke questionnaire. Multiple linear regression models (adjustments include age, sex, BMI, site, season, retirement, and dietary intake) were used to determine associations between the PA spectrum and hepatic insulin resistance index (HIRI), muscle insulin sensitivity index (MISI) and whole-body IR (HOMA-IR, Matsuda index). ResultsIn fully adjusted models, objectively measured total PA (standardized regression coefficient beta = 0.17, p = 0.020), light-intensity PA (beta = 0.15, p = 0.045) and moderate-to-vigorous intensity PA (beta = 0.13, p = 0.048) were independently associated with Matsuda index, but not HOMA-IR (p > 0.05). A higher questionnaire-derived sport index and leisure index were associated with significantly lower whole-body IR (Matsuda, HOMA-IR) in men but not in women. Results varied across tissues: more time spent sedentary (beta = -0.24, p = 0.045) and a higher leisure index (beta = 0.14, p = 0.034) were respectively negatively and positively associated with MISI, but not HIRI. A higher sport index was associated with lower HIRI (beta = -0.30, p = 0.007, in men only). ConclusionWhile we confirm a beneficial association between PA and whole-body IR, our findings indicate that associations between the PA spectrum and IR seem distinct depending on the primary site of insulin resistance (muscle or liver)

Corrigendum: The PERSonalized Glucose Optimization Through Nutritional Intervention (PERSON) Study: Rationale, Design and Preliminary Screening Results

In the original article, there was a mistake in Supplementary Tables 3 and 4. Some numbers in these tables were incorrect. The corrected tables Supplementary Tables 3 and 4 appear below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated