[Risk stratification in pulmonary arterial hypertension - implementation of an internet-based risk calculator to guide treatment]. / Prognostisk riskstratifiering vid pulmonell arteriell hypertension.

The 2022 ESC/ERS pulmonary hypertension guidelines recommend multiparametric risk stratification at diagnosis and follow-up to guide treatment in pulmonary arterial hypertension (PAH). The goal is to maintain or achieve a low-risk status, corresponding to a 1-year mortality < 5%. Risk assessment is, however, underutilized in clinical practice, and applied only by 60% of clinicians. To overcome the barrier of underutilization and facilitate risk assessment, we have established a comprehensive internet-based risk stratification calculator (https://www.svefph.se/risk-stratification).

Plasma tumour necrosis factor-alpha-related proteins in prognosis of heart failure with pulmonary hypertension.

AIMS: Patients with heart failure (HF) exhibit poor prognosis, which is further deteriorated by pulmonary hypertension (PH), with negative impact on morbidity and mortality. As PH due to left HF (LHF-PH) is among the most common causes of PH, there is an urge according to the 2021 European Society of Cardiology HF guidelines to find new biomarkers that aid in prognostication of this patient cohort. Given the role of tumour necrosis factor-alpha (TNF-α) in HF progression, we aimed to investigate the prognostic value of plasma proteins related to TNF-α in patients with LHF-PH, in relation to haemodynamic changes following heart transplantation (HT). METHODS AND RESULTS: Twenty TNF-α-related plasma proteins were analysed using proximity extension assay in healthy controls (n = 20) and patients with LHF-PH (n = 67), before and 1 year after HT (n = 19). Plasma levels were compared between the groups, and the prognostic values were determined using Kaplan-Meier and Cox regression analyses. Plasma levels of lymphotoxin-beta receptor (LTBR), TNF receptor superfamily member 6B (TNFRSF6B), and TNF-related apoptosis-inducing ligand receptors 1 and 2 (TRAIL-R1 and TRAIL-R2, respectively) were higher in LHF-PH pre-HT vs. controls (P < 0.0001), as well as higher in pre-HT vs. post-HT (P < 0.001). The elevated pre-HT levels of LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 decreased towards the levels of healthy controls after HT. Higher preoperative levels of LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 in LHF-PH were associated with worse survival rates (P < 0.002). In multivariate Cox regression models, each adjusted for age and sex, LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 predicted mortality (P < 0.002) [hazard ratio (95% confidence interval): 1.12 (1.04-1.19), 1.01 (1.004-1.02), 1.28 (1.14-1.42), and 1.03 (1.02-1.04), respectively]. CONCLUSIONS: Elevated pre-HT plasma levels of the TNF-α-related proteins LTBR, TNFRSF6B, TRAIL-R1, and TRAIL-R2 in LHF-PH decreased 1 year after HT, displaying a normalization pattern towards the levels of the healthy controls. These proteins were also prognostic, where higher levels were associated with worse survival rates in LHF-PH, providing new insight in their potential role as prognostic biomarkers. Larger studies are warranted to validate our findings and to investigate their possible pathobiological mechanisms in LHF-PH.

Plasma TRAIL and ANXA1 in diagnosis and prognostication of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare vasculopathy, with high morbidity and mortality. The sensitivity of the current european society of cardiology/european respiratory society (ESC/ERS) risk assessment strategy may be improved by the addition of biomarkers related to PAH pathophysiology. Such plasma-borne biomarkers may also reduce time to diagnosis, if used as diagnostic tools in patients with unclear dyspnea, and in guiding treatment decisions. Plasma levels of proteins related to tumor necrosis factor (TNF), inflammation, and immunomodulation were analyzed with proximity extension assays in patients with PAH (n = 48), chronic thromboembolic pulmonary hypertension (PH; CTEPH, n = 20), PH due to left heart failure (HF) with preserved (HFpEF-PH, n = 33), or reduced (HFrEF-PH, n = 36) ejection fraction, HF without PH (n = 15), and healthy controls (n = 20). TNF-related apoptosis-inducing ligand (TRAIL) were lower in PAH versus the other disease groups and controls (p < 0.0082). In receiver operating characteristics analysis, TRAIL levels identified PAH from the other disease groups with a sensitivity of 0.81 and a specificity of 0.53 [area under the curve: 0.70; (95% confidence interval, CI: 0.61-0.79; p < 0.0001)]. In both single (p < 0.05) and multivariable Cox regression models Annexin A1 (ANXA1) [hazard ratio, HR: 1.0367; (95% CI: 1.0059-1.0684; p = 0.044)] and carcinoembryonic antigen-related cell adhesion molecule 8 [HR: 1.0603; (95% CI: 1.0004-1.1237; p = 0.0483)] were significant predictors of survival, adjusted for age, female sex and ESC/ERS-initial risk score. Low plasma TRAIL predicted PAH among patients with dyspnea and differentiated PAH from those with CTEPH, HF with and without PH; and healthy controls. Higher plasma ANXA1 was associated with worse survival in PAH. Larger multicenter studies are encouraged to validate our findings.

Adrenomedullin peptides and precursor levels in relation to haemodynamics and prognosis after heart transplantation.

AIMS: Heart failure (HF) is a frequent condition in the elderly, further complicated by associated pulmonary hypertension (PH), with impact on morbidity and mortality. Plasma proteins associated with cardiovascular disease, related to inflammation, neurohormonal changes, and myocyte stress, pathways recognized in the pathophysiology of HF, may provide information on disease severity and prognosis. We aimed to investigate such cardiovascular proteins and their relationship to haemodynamics before and 1 year after heart transplantation (HT), as well as their prognostic value in advanced HF with PH. METHODS AND RESULTS: In 20 healthy controls and 67 patients with HF and PH, before and 1 year after HT, N-terminal pro-brain natriuretic peptide (NT-proBNP) and 18 cardiovascular proteins were analysed with proximity extension assay. Right heart catheterization was used to measure the haemodynamics of the HF patients pre-operatively and at 1 year follow-up after HT. Prognosis was estimated using Kaplan-Meier and Cox regression analyses. Out of 18 plasma proteins, 11 proteins including adrenomedullin peptides and precursor levels (ADM) and protein suppression of tumourigenicity 2 receptor were elevated before HT compared with healthy controls and had decreased 1 year after HT. The decrease in plasma levels 1 year after HT was towards the healthy controls' levels. The decrease in ADM levels before vs. after HT correlated with decreased mean right atrial pressure (rs  = 0.61; P = 0.0077), decreased NT-proBNP (rs  = 0.75; P = 0.00025), and decreased stroke volume index (rs  = -0.52; P = 0.022). High levels of pre-operative plasma ADM were associated with worse event-free survival (HT or death), as well as survival compared with low ADM levels (log-rank P value = 0.023 and 0.0225, respectively). Univariable Cox regression analysis demonstrated that ADM levels were associated with survival, hazard ratio (HR) 1.007 (95% confidence interval (CI): 1.00-1.015, P = 0.049), and the association remained after adjusting for NT-proBNP, HR 1.01 (95% CI: 1.00-1.021, P = 0.041). CONCLUSIONS: Elevated plasma levels of ADM may be a marker of pressure/volume overload in HF patients with PH, as well as long-term prognosis after HT. In line with previous studies, our findings additionally confirm that ADM may be a marker of venous congestion in HF. Further studies are encouraged to establish a deeper understanding of the properties of ADM and its relationship with HF and PH, in order to potentially facilitate clinical management of HF and associated PH.

Evaluation of the European Society of Cardiology/European Respiratory Society derived three- and four-strata risk stratification models in pulmonary arterial hypertension: introducing an internet-based risk stratification calculator.

Aims: Estimation of prognosis in pulmonary arterial hypertension (PAH) has been influenced by that various risk stratification models use different numbers of prognostic parameters, as well as the lack of a comprehensive and time-saving risk assessment calculator. We therefore evaluated the various European Society of Cardiology (ESC)-/European Respiratory Society (ERS)-based three- and four-strata risk stratification models and established a comprehensive internet-based calculator to facilitate risk assessment. Methods and results: Between 1 January 2000 and 26 July 2021, 773 clinical assessments on 169 incident PAH patients were evaluated at diagnosis and follow-ups. Risk scores were calculated using the original Swedish Pulmonary Arterial Hypertension Registry (SPAHR)/Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) three-strata model, the updated SPAHR three-strata model with divided intermediate risk, and the simplified three-parameter COMPERA 2.0 four-strata model. The original SPAHR/COMPERA and the updated SPAHR models were tested for both 3-6 and 7-11 available parameters, respectively. Prognostic accuracy [area under the receiver operating characteristic (ROC) curve (AUC)] and Uno's cumulative/time-dependent C-statistics (uAUC) were calculated for 1-, 3-, and 5-year mortality. At baseline, both the original SPAHR/COMPERA and the updated SPAHR models, using up to six parameters, provided the highest accuracy (uAUC = 0.73 for both models) in predicting 1-, 3-, and 5-year mortality. At follow-ups, the updated SPAHR model with divided intermediate risk (7-11 parameters) provided the highest accuracy for 1-, 3-, and 5-year mortality (uAUC = 0.90), followed by the original SPAHR/COMPERA model (7-11 parameters) (uAUC = 0.88) and the COMPERA 2.0 model (uAUC = 0.85). Conclusions: The present study facilitates risk assessment in PAH by introducing a comprehensive internet-based risk score calculator (https://www.svefph.se/risk-stratification). At baseline, utilizing the original or the updated SPAHR models using up to six parameters was favourable, the latter model additionally offering sub-characterization of the intermediate risk group. Our findings support the 2022 ESC/ERS pulmonary hypertension guidelines' strategy for risk stratification suggesting the utilization of a three-strata model at baseline and a simplified four-strata model at follow-ups. Our findings furthermore support the utility of the updated SPAHR model with divided intermediate risk, when a more comprehensive assessment is needed at follow-ups, complementing the three-parameter COMPERA 2.0 model. Larger multi-centre studies are encouraged to validate the utility of the updated SPAHR model. Take home message: By introducing an internet-based risk score calculator (https://www.svefph.se/risk-stratification), risk assessment is facilitated. Our results support the 2022 ESC/ERS pulmonary hypertension guidelines' risk stratification strategy, additionally suggesting the updated SPAHR three-strata model with divided intermediate risk, as a promising complement to the new simplified three-parameter COMPERA 2.0 four-strata strategy, when a more comprehensive overview is needed.

[Structured evaluation of unclear dyspnea - of great importance to early identify patients with PAH and CTEPH and improve prognosis]. / Andfåddhet potentiellt allvarligt ­ kräver strukturerad utredning.

Dyspnea is a common distressing symptom which may be a sign of a critically threatening condition and has been linked with increased hospitalizations, reduced exercise tolerance and increased mortality. The current neuropsychological model suggests that dyspnea arises due to an imbalance between respiratory drive and achieved ventilation. Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are rare but detrimental conditions, with high morbidity and mortality, where early diagnosis and treatment initiation significantly improve outcome. These conditions are often accompanied by a diagnostic delay, which for PAH has not improved since the 1980s, underlining the importance of early evaluation and referral to specialists. In the present work, differential diagnoses of dyspnea are discussed along with a proposal on how a structured evaluation should be performed early to minimize the diagnostic delay in PAH and CTEPH and improve outcome.

Plasma Biomarkers for Clinical Assessment of Bone Mineral Density in Heart Transplanted Patients-A Single-Center Study at Skåne University Hospital in Lund.

We aimed to identify plasma biomarkers that predict changes in bone mineral density (BMD) and increase the understanding of impaired BMD after heart transplantation (HT). Twenty-eight adult patients were included. Data, including densitometry and 29 plasma proteins, before and 1 year after HT were analyzed. Pre-HT plasma levels of fibroblast growth factor 23 (FGF23) correlated with post-HT T score in lumbar spine, adjusted for age, gender, and BMI (1.72 [95% CI 1.33; 2.22], p = 0.011). Change (∆; post-HT-pre-HT) in plasma levels of melusin correlated to ∆T score from the lumbar spine (p = 0.028). ∆plasma levels of TR-AP, ITGB2, and Stromelysin-1 correlated to ∆T score from the femoral neck (p < 0.05). However, no correlations remained after adjustments for age, gender, and BMI. In conclusion, elevated plasma FGF23 pre-HT predicted an increase in lumbar BMD after HT. However, the results are surprising since FGF23 is known to be inversely correlated with BMD. This may partly be explained by the complex pathophysiology in this particular cohort. Due to the explorative nature of the study and the small sample size, further investigations of biochemical markers on bone metabolism in this patient population are encouraged.

Elevated plasma WIF-1 levels are associated with worse prognosis in heart failure with pulmonary hypertension.

AIMS: Heart failure (HF) is a progressive condition that is becoming more prevalent in the ageing population. Pulmonary hypertension is a common complicating factor in HF and negatively impacts survival. Plasma biomarkers are a potential method for determining the prognosis of patients with left heart failure with pulmonary hypertension (LHF-PH). We aimed to analyse the prognostic capability of 33 proteins related to, among other pathways, inflammation, coagulation, and Wnt signalling in LHF-PH. METHODS: Plasma levels of 33 proteins were analysed using proximity extension assay from the plasma of 20 controls and 67 LHF-PH patients, whereof 19 underwent heart transplantation (HT). Haemodynamics in the patients were assessed using right heart catheterization. RESULTS: Eleven proteins had elevated plasma levels in LHF-PH compared with controls (P < 0.01), which decreased towards the controls' levels after HT (P < 0.01). Survival analysis of these proteins showed that elevated plasma levels of growth hormone, programmed cell death 1 ligand 2, tissue factor pathway inhibitor 2, and Wnt inhibitory factor 1 (WIF-1) were associated with worse transplantation-free survival in LHF-PH (P < 0.05). When adjusted for age, sex and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels using multivariable cox regressions, only WIF-1 remained prognostic [hazard ratio (95% confidence interval)] [1.013 (1.001-1.024)]. WIF-1 levels in LHF-PH patients also correlated with the mean right atrial pressure (rs  = 0.42; P < 0.01), stroke volume index (rs  = 0.41; P < 0.01), cardiac index (rs  = -0.42; P < 0.01), left ventricular stroke work index (rs  = -0.41; P < 0.01), and NT-proBNP (rs  = 0.63; P < 0.01). CONCLUSIONS: The present study demonstrated that LHF-PH patients have higher plasma WIF-1 levels than healthy controls, suggesting that plasma WIF-1 may be a potential future prognostic biomarker in LHF-PH. Its prognostic capability could be further refined by including it in a multi-marker panel. Further studies are needed to establish the potential role of WIF-1 in LHF-PH pathophysiology in larger cohorts to determine its clinical applicability.

Data on plasma tumour and metabolism related proteins' potential in differentiation of HFpEF-PH from PAH and in prognosis of left heart failure patients with pulmonary hypertension.

The data in the current paper constitutes supplementary material to our article entitled "Plasma tumour and metabolism related biomarkers AMBP, LPL and Glyoxalase I differentiate heart failure with preserved ejection fraction with pulmonary hypertension from pulmonary arterial hypertension" Ahmed et al. (2021). The study investigated 69 plasma tumour- and metabolism related proteins in healthy controls (n = 20) and in 115 patients of whom 48 had pulmonary arterial hypertension (PAH; n = 48) and 67 with left heart failure with pulmonary hypertension (LHF-PH) [heart failure with- preserved ejection fraction-PH (HFpEF-PH; n = 31) and reduced ejection fraction-PH (HFrEF-PH; n = 36)]. The haemodynamic data were obtained with right heart catheterization, and clinical data from medical records. The present article describe the plasma levels of tumour- and metabolism related proteins, analyzed with proximity extension assay, along with their uni- and multivariable diagnostic and prognostic potential. High sRAGE levels univariably emerged as a negative prognostic marker in LHF-PH.

Higher plasma IL-6 and PTX3 are associated with worse survival in left heart failure with pulmonary hypertension.

Introduction: Left heart failure (LHF) is commonly complicated by pulmonary hypertension (PH), increasing morbidity and mortality. The present study aimed to evaluate the prognostic value of inflammatory proteins in LHF with PH (LHF-PH). Materials and methods: The levels of 65 plasma proteins, analysed with proximity extension assay, were compared between healthy controls (n = 20), patients with LHF-PH (n = 67) comprising both HFpEF-PH (n = 31) and HFrEF-PH (n = 36), and in a LHF subpopulation before and after heart transplantation (HT, n = 19). Haemodynamic parameters were measured using right heart catheterization. Results: Plasma levels of Interleukin 6 (IL-6) and Pentraxin related protein PTX3 (PTX3) were elevated in LHF-PH vs. controls (p < 0.001), and these decreased after HT compared to before HT (p < 0.001). Plasma IL-6 and PTX3 correlated to elevated NT-proBNP (r = 0.44, p = 0.0002 and r = 0.4, p = 0.0009, respectively). Additionally, IL-6 correlated with mean pulmonary arterial pressure (r = 0.4, p = 0.0009) and mean right atrial pressure (r = 0.51, p < 0.0001). Higher levels of IL-6 and PTX3 were associated with worse survival rates in patients with LHF-PH (Log rank p < 0.01). Discussion: In patients with LHF-PH, higher plasma levels of IL-6 and PTX3 were associated with worse survival rates. Future larger studies to validate and investigate the direct clinical applicability of IL-6 and PTX3 as potential prognostic biomarkers are encouraged.

Plasma tumour and metabolism related biomarkers AMBP, LPL and Glyoxalase I differentiate heart failure with preserved ejection fraction with pulmonary hypertension from pulmonary arterial hypertension.

BACKGROUND: Discrimination of heart failure with preserved ejection fraction with pulmonary hypertension (HFpEF-PH) from pulmonary arterial hypertension (PAH) is crucial for clinical management but may be challenging due to similarities in clinical and comorbid characteristics. We aimed to investigate tumour and metabolism related proteins in differentiating HFpEF-PH from PAH. METHODS: Sixty-nine tumour and metabolism plasma proteins were analysed with proximity extension assay in heathy controls (n = 20), patients with PAH (n = 48) and LHF-PH (n = 67) [HFpEF-PH (n = 31) and HF reduced EF-PH (n = 36)]. Haemodynamics were assessed with right heart catheterization. RESULTS: The plasma levels of alpha-1-microglobulin/bikunin precursor (AMBP) and lipoprotein lipase (LPL), were higher in HFpEF-PH compared to healthy controls (p < 0.01), HFrEF-PH (p < 0.05), and PAH (p < 0.001). Glyoxalase I levels were higher in HFpEF-PH and HFrEF-PH compared to controls (p < 0.001) and PAH (p < 0.001). Each of plasma AMBP, LPL, and glyoxalase I, adjusted for age and sex in multivariable logistic regression models, could differentiate HFpEF-PH from PAH, with areas under the receiver operating characteristic curve (AUC) of 0.81, 0.84 and 0.79, respectively. The combination of AMBP, LPL and glyoxalse I yielded the largest AUC of 0.87 [95% confidence interval (0.79-0.95)] in discriminating HFpEF-PH from PAH, with a sensitivity of 87.1% and a specificity of 85.4%. In HFpEF-PH, the plasma levels of AMBP correlated with pulmonary arterial wedge pressure (rs = -0.42, p = 0.018). CONCLUSIONS: Plasma AMBP, LPL and glyoxalase I may facilitate the distinction of HFpEF-PH from PAH. Larger clinical studies are encouraged to confirm and validate our findings.

Plasma ADAMTS13 and von Willebrand factor in diagnosis and prediction of prognosis in pulmonary arterial hypertension.

To improve outcome in pulmonary arterial hypertension, earlier diagnosis and better prognostic assessments are required. We aimed to investigate the diagnostic and prognostic potential of plasma proteins related to pathways recognized in pulmonary arterial hypertension including coagulation, inflammation, and metabolism. Forty-two proteins were analysed with proximity extension assay from plasma of 20 healthy controls and 150 patients, including (pulmonary arterial hypertension, n = 48, whereof 33 also during early treatment follow-ups); chronic thromboembolic pulmonary hypertension (CTEPH, n = 20); pulmonary hypertension (PH) due to heart failure (HF) with preserved ejection fraction (HFpEF-PH, n = 31); PH due to HF with reduced ejection fraction (HFrEF-PH, n = 36); and HF without PH (Dyspnoea/HF-non-PH, n = 15). Patients' haemodynamics were assessed by right heart catheterization. Plasma ADAMTS13 in incident pulmonary arterial hypertension was lower compared to the healthy controls (p = 0.055), as well as CTEPH (p < 0.0001), HFrEF-PH (p < 0.0001), HFrEF-PH (p < 0.0001), and Dyspnoea/HF-non-PH (p < 0.0001). Adjusted for age and sex, ADAMTS13 discriminated pulmonary arterial hypertension from the other disease groups with an AUC of 0.91 (sensitivity = 87.5%, and specificity = 78.4%). Higher plasma von Willebrand factor was associated with worse survival (log-rank p = 0.0029), and a higher mortality rate (adjusted hazard ratio 1.002, 95% confidence interval 1-1.004; p = 0.041). Adjusted for age, sex, and combined with the ESC/ERS risk score, von Willebrand factor predicted mortality (median follow-up 3.6 years) in pulmonary arterial hypertension with an AUC of 0.94 (sensitivity = 81.3%, and specificity=93.8%). ADAMTS13 may be a promising biomarker for early detection of PAH and von Willebrand factor as a candidate prognostic biomarker. The putative additional value of von Willebrand factor to the European multiparametric risk assessment strategy remains to be elucidated.

Thoracic Anesthesia during the COVID-19 Pandemic: 2021 Updated Recommendations by the European Association of Cardiothoracic Anaesthesiology and Intensive Care (EACTAIC) Thoracic Subspecialty Committee.

The novel coronavirus pandemic has radically changed the landscape of normal surgical practice. Lifesaving cancer surgery, however, remains a clinical priority, and there is an increasing need to fully define the optimal oncologic management of patients with varying stages of lung cancer, allowing prioritization of which thoracic procedures should be performed in the current era. Healthcare providers and managers should not ignore the risk of a bimodal peak of mortality in patients with lung cancer; an imminent spike due to mortality from acute coronavirus disease 2019 (COVID-19) infection, and a secondary peak reflecting an excess of cancer-related mortality among patients whose treatments were deemed less urgent, delayed, or cancelled. The European Association of Cardiothoracic Anaesthesiology and Intensive Care Thoracic Anesthesia Subspecialty group has considered these challenges and developed an updated set of expert recommendations concerning the infectious period, timing of surgery, vaccination, preoperative screening and evaluation, airway management, and ventilation of thoracic surgical patients during the COVID-19 pandemic.

Effect of magnesium sulphate on the intracranial pressure of preeclampsia patients using ultrasound-guided optic nerve sheath diameter: A pilot study.

BACKGROUND: Increased intracranial pressure (ICP) is a known complication of pre-eclampsia with severe features. The use of magnesium sulphate (MgSO4) is the standard treatment and is associated with marked reduction of cerebral perfusion pressure (CPP) and prevention of cerebral damage. Optic nerve sheath diameter (ONSD) ultrasonography is a bedside tool used to reflect changes in the ICP. The aim of this study is to detect the effect of MgSO4 administration on ICP in severe preeclampsia through measuring changes in the ONDS. METHODS: Thirty pregnant female patients suffering from severe pre-eclampsia were enrolled in this prospective pilot study. Ultrasound measurement of ONSD was measured before the commencement of MgSO4 and after 1, 6, and 24 h after the administration. RESULTS: There was a significant difference in ONSD measurements between that at baseline and post magnesium administration at 1, 6, and 24 h (P-value 0.001). Additionally, a significant difference in measurements between 1 and 6 and 6 and 24 h after magnesium initiation (P-value 0.001). CONCLUSIONS: Ultrasound ONSD measurement in patients with severe preeclampsia is a non-invasive easy tool to detect increased intracranial pressure and monitor the response to magnesium sulphate infusion.

A Comparative Study of the Use of Dexamethasone, N-acetyl Cysteine, and Theophylline to Ameliorate Renal Ischemia-Reperfusion Injury in Experimental Rat Models: A Biochemical and Immuno-histochemical Approach.

Renal ischemia-reperfusion injury (IRI) is commonly encountered in clinical practice during renal transplantation. In a trial to find the drug that best safeguards the kidney against IRI, dexamethasone (Dex), N-acetyl cysteine (NAC), and theophylline (Theo) were tested in experimental rat models. This study included 105 adult male albino rats, which were randomly assigned to the following five groups: Group I - sham-operated, n = 5, Group II - IRI n = 25, Group III - IRI + Dex n = 25, Group IV - IRI + NAC n = 25, and Group V -IRI + Theo n = 25. IRI was induced for 40 min followed by reperfusion. Rats were sacrificed 1, 2, 4, 6, and 24 h after reperfusion. This was preceded by blood and urine sampling for biochemical study of serum Cystatin C (Cys C), serum creatinine, and urinary Cys C. Kidneys were processed for histopathological evaluation and immune-histochemical staining for Cys C. The expression of Cys C in the proximal tubular cells was significantly lower in the IRI group compared to that of the sham group. There was a significant rise in the levels of serum and urinary Cys C after 1 h in the IRI group, while the rise in creatinine occurred later. Dex was superior to NAC and Theo 24 h after the IR insult, and the serum levels of creatinine and Cys C were significantly lower in this group than the other two drug groups (P <0.001 in both cases). Our study revealed a clear benefit for the use of Dex to ameliorate IRI over NAC and Theo if used immediately following the insult. The effect is evident 24-h after its use. The role of serum Cys C as an early marker of acute kidney injury compared to serum creatinine is confirmed.

Elevated plasma endocan and BOC in heart failure patients decrease after heart transplantation in association with improved hemodynamics.

BACKGROUND: The prevalence of heart failure (HF) is rising with ageing population and constitutes a major health problem globally. A common complication of HF is pulmonary hypertension (PH) which negatively impacts survival. A pathophysiological association between HF and PH with tumorigenic processes has been suggested. We aimed to identify the plasma levels of, and the association between tumour-related proteins and hemodynamic improvements in patients with HF and PH due to left heart disease (LHD) before and 1-year after heart transplantation (HT). METHODS: Forty-eight tumour-related proteins were measured with proximity extension assay in plasma from 20 controls and 26 HF patients before and 1-year after HT. Patients' hemodynamics were measured with right heart catheterization. RESULTS: Out of 48 proteins, specifically, plasma levels of endocan and brother of CDO (BOC) were elevated in end-stage HF patients compared to controls (p < 0.001), but decreased after HT (p < 0.01), towards controls' levels. The decrease of endocan levels after HT correlated with improved mean pulmonary arterial pressure (rs = 0.80, p < 0.0001), pulmonary arterial wedge pressure (rs = 0.63, p = 0.0012), and pulmonary vascular resistance (rs = 0.70, p < 0.001). The decrease and normalization of BOC after HT correlated with decreased mean right atrial pressure (rs = 0.61 p = 0.0015) and NT-proBNP (rs = 0.57, p = 0.0022), as well as increased cardiac index (rs = - 0.51, p = 0.0086) and left-ventricular stroke work index (rs = - 0.57, p = 0.0039). CONCLUSION: Our results suggest that (i) plasma endocan in HF may reflect the state of pulmonary vascular congestion and PH-LHD, whereas (ii) plasma BOC may reflect the cardiac function and the hemodynamic overload in HF. The exact role of these proteins and their clinical applicability as biomarkers in HF and PH-LHD ought to be investigated in larger cohorts.