Early detection of anastomotic leakage after pancreatoduodenectomy with microdialysis catheters: an observational Study

Background Microdialysis catheters can detect focal inflammation and ischemia, and thereby have a potential for early detection of anastomotic leakages after pancreatoduodenectomy. The aim was to investigate whether microdialysis catheters placed near the pancreaticojejunostomy can detect leakage earlier than the current standard of care. Methods Thirty-five patients with a median age 69 years were included. Two microdialysis catheters were placed at the end of surgery; one at the pancreaticojejunostomy, and one at the hepaticojejunostomy. Concentrations of glucose, lactate, pyruvate, and glycerol were analyzed hourly in the microdialysate during the first 24 h, and every 2–4 h thereafter. Results Seven patients with postoperative pancreatic fistulae (POPF) had significantly higher glycerol levels (P 400 μmol/L during the first 12 postoperative hours detected patients with POPF with a sensitivity of 100% and a specificity of 93% (P < 0.001). After 24 h, lactate and lactate-to-pyruvate ratio were significantly higher (P < 0.05) and glucose was significantly lower (P < 0.05) in patients with POPF. Conclusion High levels of glycerol in microdialysate was an early detector of POPF. The subsequent inflammation was detected as increase in lactate and lactate-to-pyruvate ratio and a decrease in glucose (NCT03627559).publishedVersio

Increased arterial stiffness in pre-eclamptic pregnancy at term and early and late postpartum: a combined echocardiographic and tonometric study

BACKGROUND Pre-eclampsia (PE) is characterized by hypertension and proteinuria, and complicates from 3%-10% of all pregnancies. The hemodynamic pathophysiology of the heart and systemic arteries in pre-eclamptic patients has not been well described. We therefore performed a comprehensive comparison of the systemic arterial properties at term and at 6 months postpartum in women with PE and in women with normal pregnancy (NP) and in nonpregnant women with a previous pre-eclamptic pregnancy (PPEP). METHODS The comparison included 40 patients with PE, 40 others with a PPEP (at 3.5 +/- 1.0 years postpartum), and 65 women who had had an NP. Noninvasive estimates of blood flow and pressure in the aortic root were made with echocardiography and calibrated right subclavian artery pulse traces obtained through tonometry. Total arterial compliance (C), arterial elastance (Ea), characteristic impedance (Z0), and peripheral arterial resistance (R) were estimated both through the use of a three-element Windkessel model and Fourier analysis of pressure and flow data. RESULTS At term, Z0, Ea, and R were higher by 37%, 25%, and 23%, respectively (all P < 0.05) in women with PE than in those with an NP, and C was lower by 12% (P < 0.05). The values of Z0, Ea, and R remained elevated at 6 months postpartum in women who had had PE, and were also elevated in those with a PPEP, as compared to their values in NP. CONCLUSIONS Our results demonstrate that pre-eclamptic pregnancies are characterized by a higher resistance throughout the arterial system. The altered arterial properties (Ea, Z0, and R) persisted at 6 months after PE and were also elevated at 3 years postpartum in women with a PPEP, indicating that PE induces long-standing cardiovascular disturbances

Systemic arterial response and ventriculo-arterial interaction during normal pregnancy

BACKGROUND: During normal pregnancy (NP), cardiac output (CO) increases, and blood pressure and systemic vascular resistance are reduced. We wanted to evaluate systemic arterial properties and interaction between the left ventricle (LV) and systemic arteries during NP. The role of systemic arteries and their interaction with LV-function in this hemodynamic response, lack description. METHODS: We used noninvasive methods to study 65 healthy women (32 +/- 5 years) with NP repeatedly at gestational weeks 14-16, 22-24, 36, and 6 months postpartum (PP). Aortic root pressure and flow were obtained by calibrated right subclavian artery pulse traces and aortic annular Doppler flow recordings. Arterial properties were described by estimates of total arterial compliance (C), proximal aortic stiffness (characteristic impedance (Z(0))), arterial elastance (Ea), and peripheral arterial resistance (R). Ventriculo-arterial coupling (VAC) was characterized by the ratio between arterial (EaI) and LV (ELVI) elastance index. RESULTS: During NP, CO increased by 20% due to increased heart rate and stroke volume. Mean arterial pressure was reduced by 10% (P < 0.001) as compared to 6 months PP. R was reduced by 5% (P < 0.01), Z(0) trended lower and C higher. EaI decreased (P < 0.01) and ELVI was reduced to a higher extent resulting in 29% increase of EaI/ELVI during NP (P < 0.01). CONCLUSIONS: During NP there is an increase in CO, and decrease in blood pressure and R whereas central aortic properties are less altered. The increased VAC index (EaI/ELVI) during NP indicates a decrease in LV-function not fully compensated for by vascular adaptation

Elevated levels of the secreted wingless agonist R-spondin 3 in preeclamptic pregnancies

Objective: Preeclampsia is a syndrome characterized by hypertension and poor placental development. The developmental wingless (Wnt) pathway plays an important role in placental development and we hypothesized that Wnt signaling would be dysregulated in preeclampsia. Methods: To elucidate aberrations in the Wnt signaling pathway we conducted a pathway analysis on placental mRNA in late-onset preeclampsia and normal pregnancy from the STORK study [n = 10 in each group, RNA sequencing (RNAseq)] to identify differentially expressed genes. In addition, we compared circulating levels of secreted Wnt agonists and antagonists at term pregnancy and 6 months postpartum from an acute preeclampsia study (preeclampsia n = 34, normal pregnancy n = 61). Results: We found circulating and placental mRNA levels of the secreted Wnt agonist R-spondin 3 (RSPO3) at term elevated in preeclampsia. Increased plasma RSPO3 was associated with high mean arterial pressure. Further, pathway analysis of placental tissue revealed elevated mRNA levels of upstream ligands WNT6 and WNT10A and frizzled receptors 2 and 4 in preeclampsia and downstream activation of the noncanonical Ca2+/NFAT pathway. Finally, plasma dickkopf 3 was decreased in preeclampsia 6 months postpartum. Conclusion: We identify a potential role for RSPO3 and activation of noncanonical Wnt signaling in preeclampsia

Circulatory Response to Rapid Volume Expansion and Cardiorespiratory Fitness in Fontan Circulation

Abstract The role of dysfunction of the single ventricle in Fontan failure is incompletely understood. We aimed to evaluate hemodynamic responses to preload increase in Fontan circulation, to determine whether circulatory limitations in different locations identified by experimental preload increase are associated with cardiorespiratory fitness (CRF), and to assess the impact of left versus right ventricular morphology. In 38 consecutive patients (median age = 16.6 years, 16 females), heart catheterization was supplemented with a rapid 5-mL/kg body weight volume expansion. Central venous pressure (CVP), ventricular end-diastolic pressure (VEDP), and peak systolic pressure were averaged for 15‒30 s, 45‒120 s, and 4‒6 min (steady state), respectively. CRF was assessed by peak oxygen consumption (VO 2peak ) and ventilatory threshold (VT). Median CVP increased from 13 mmHg at baseline to 14.5 mmHg ( p  &lt; 0.001) at steady state. CVP increased by more than 20% in eight patients. Median VEDP increased from 10 mmHg at baseline to 11.5 mmHg ( p  &lt; 0.001). Ten patients had elevated VEDP at steady state, and in 21, VEDP increased more than 20%. The transpulmonary pressure difference (CVP‒VEDP) and CVP were consistently higher in patients with right ventricular morphology across repeated measurements. CVP at any stage was associated with VO 2peak and VT. VEDP after volume expansion was associated with VT. Preload challenge demonstrates the limitations beyond baseline measurements. Elevation of both CVP and VEDP are associated with impaired CRF. Transpulmonary flow limitation was more pronounced in right ventricular morphology. Ventricular dysfunction may contribute to functional impairment after Fontan operation in young adulthood. ClinicalTrials.gov identifier NCT0237885

Circulatory response to rapid volume expansion and cardiorespiratory fitness in Fontan circulation

The role of dysfunction of the single ventricle in Fontan failure is incompletely understood. We aimed to evaluate hemodynamic responses to preload increase in Fontan circulation, to determine whether circulatory limitations in different locations identified by experimental preload increase are associated with cardiorespiratory fitness (CRF), and to assess the impact of left versus right ventricular morphology. In 38 consecutive patients (median age = 16.6 years, 16 females), heart catheterization was supplemented with a rapid 5-mL/kg body weight volume expansion. Central venous pressure (CVP), ventricular end-diastolic pressure (VEDP), and peak systolic pressure were averaged for 15‒30 s, 45‒120 s, and 4‒6 min (steady state), respectively. CRF was assessed by peak oxygen consumption (VO2peak) and ventilatory threshold (VT). Median CVP increased from 13 mmHg at baseline to 14.5 mmHg (p < 0.001) at steady state. CVP increased by more than 20% in eight patients. Median VEDP increased from 10 mmHg at baseline to 11.5 mmHg (p < 0.001). Ten patients had elevated VEDP at steady state, and in 21, VEDP increased more than 20%. The transpulmonary pressure difference (CVP‒VEDP) and CVP were consistently higher in patients with right ventricular morphology across repeated measurements. CVP at any stage was associated with VO2peak and VT. VEDP after volume expansion was associated with VT. Preload challenge demonstrates the limitations beyond baseline measurements. Elevation of both CVP and VEDP are associated with impaired CRF. Transpulmonary flow limitation was more pronounced in right ventricular morphology. Ventricular dysfunction may contribute to functional impairment after Fontan operation in young adulthood

Early detection of anastomotic leakage after pancreatoduodenectomy with microdialysis catheters: an observational Study

Background Microdialysis catheters can detect focal inflammation and ischemia, and thereby have a potential for early detection of anastomotic leakages after pancreatoduodenectomy. The aim was to investigate whether microdialysis catheters placed near the pancreaticojejunostomy can detect leakage earlier than the current standard of care. Methods Thirty-five patients with a median age 69 years were included. Two microdialysis catheters were placed at the end of surgery; one at the pancreaticojejunostomy, and one at the hepaticojejunostomy. Concentrations of glucose, lactate, pyruvate, and glycerol were analyzed hourly in the microdialysate during the first 24 h, and every 2–4 h thereafter. Results Seven patients with postoperative pancreatic fistulae (POPF) had significantly higher glycerol levels (P 400 μmol/L during the first 12 postoperative hours detected patients with POPF with a sensitivity of 100% and a specificity of 93% (P < 0.001). After 24 h, lactate and lactate-to-pyruvate ratio were significantly higher (P < 0.05) and glucose was significantly lower (P < 0.05) in patients with POPF. Conclusion High levels of glycerol in microdialysate was an early detector of POPF. The subsequent inflammation was detected as increase in lactate and lactate-to-pyruvate ratio and a decrease in glucose (NCT03627559)

Acute heart failure following myocardial infarction: complement activation correlates with the severity of heart failure in patients developing cardiogenic shock

Aims Heart failure (HF) is an impending complication to myocardial infarction. We hypothesized that the degree of complement activation reflects severity of HF following acute myocardial infarction. Methods and results The LEAF trial (LEvosimendan in Acute heart Failure following myocardial infarction) evaluating 61 patients developing HF within 48 h after percutaneous coronary intervention‐treated ST‐elevation myocardial infarction herein underwent a post hoc analysis. Blood samples were drawn from inclusion to Day 5 and at 42 day follow‐up, and biomarkers were measured with enzyme immunoassays. Regional myocardial contractility was measured by echocardiography as wall motion score index (WMSI). The cardiogenic shock group (n = 9) was compared with the non‐shock group (n = 52). Controls (n = 44) were age‐matched and sex‐matched healthy individuals. C4bc, C3bc, C3bBbP, and sC5b‐9 were elevated in patients at inclusion compared with controls (P < 0.01). The shock group had higher levels compared with the non‐shock group for all activation products except C3bBbP (P < 0.05). At Day 42, all products were higher in the shock group (P < 0.05). In the shock group, sC5b‐9 correlated significantly with WMSI at baseline (r = 0.68; P = 0.045) and at Day 42 (r = 0.84; P = 0.036). Peak sC5b‐9 level correlated strongly with WMSI at Day 42 (r = 0.98; P = 0.005). Circulating endothelial cell activation markers sICAM‐1 and sVCAM‐1 were higher in the shock group during the acute phase (P < 0.01), and their peak levels correlated with sC5b‐9 peak level in the whole HF population (r = 0.32; P = 0.014 and r = 0.30; P = 0.022, respectively). Conclusions Complement activation discriminated cardiogenic shock from non‐shock in acute ST‐elevation myocardial infarction complicated by HF and correlated with regional contractility and endothelial cell activation, suggesting a pathogenic role of complement in this condition