Non-invasive assessment of stroke volume and cardiovascular parameters based on peripheral pressure waveform.

Cardiovascular diseases are the leading cause of death globally, making the development of non-invasive and simple-to-use tools that bring insights into the state of the cardiovascular system of utmost importance. We investigated the possibility of using peripheral pulse wave recordings to estimate stroke volume (SV) and subject-specific parameters describing the selected properties of the cardiovascular system. Peripheral pressure waveforms were recorded in the radial artery using applanation tonometry (SphygmoCor) in 35 hemodialysis (HD) patients and 14 healthy subjects. The pressure waveforms were then used to estimate subject-specific parameters of a mathematical model of pulse wave propagation coupled with the elastance-based model of the left ventricle. Bioimpedance cardiography measurements (PhysioFlow) were performed to validate the model-estimated SV. Mean absolute percentage error between the simulated and measured pressure waveforms was 4.0% and 2.8% for the HD and control group, respectively. We obtained a moderate correlation between the model-estimated and bioimpedance-based SV (r = 0.57, p<0.05, and r = 0.58, p<0.001, for the control group and HD patients, respectively). We also observed a correlation between the estimated end-systolic elastance of the left ventricle and the peripheral systolic pressure in both HD patients (r = 0.84, p<0.001) and the control group (r = 0.70, p<0.01). These preliminary results suggest that, after additional validation and possibly further refinement to increase accuracy, the proposed methodology could support non-invasive assessment of stroke volume and selected heart function parameters and vascular properties. Importantly, the proposed method could be potentially implemented in the existing devices measuring peripheral pressure waveforms.

Effect of time-dependent dialysate bicarbonate concentrations on acid-base and uremic solute kinetics during hemodialysis treatments.

Recent studies have suggested benefits for time-dependent dialysate bicarbonate concentrations (Dbic) during hemodialysis (HD). In this clinical trial, we compared for the first time in the same HD patients the effects of time-dependent changes with constant Dbic on acid-base and uremic solute kinetics. Blood acid-base and uremic solute concentration were measured in twenty chronic HD patients during 4-h treatments with A) constant Dbic of 35 mmol/L; B) Dbic of 35 mmol/L then 30 mmol/L; and C) Dbic of 30 mmol/L then 35 mmol/L (change of Dbic after two hours during Treatments B and C). Arterial blood samples were obtained predialysis, every hour during HD and one hour after HD, during second and third treatments of the week with each Dbic concentration profile. Blood bicarbonate concentration (blood [HCO3]) during Treatment C was lower only during the first three HD hours than in Treatment A. Overall blood [HCO3] was reduced during Treatment B in comparison to Treatment A at each time points. We conclude that a single change Dbic in the middle of HD can alter the rate of change in blood [HCO3] and pH during HD; time-dependent Dbic had no influence on uremic solute kinetics.

Quantification of Gleason Pattern 4 at MRI-Guided Biopsy to Predict Adverse Pathology at Radical Prostatectomy in Intermediate-Risk Prostate Cancer Patients.

BACKGROUND: Data on Gleason pattern 4 (GP4) amount in biopsy tissue is important for prostate cancer (PC) risk assessment. We aim to investigate which GP4 quantification method predicts adverse pathology (AP) at radical prostatectomy (RP) the best in men diagnosed with intermediate-risk (IR) PC at magnetic resonance imaging (MRI)-guided biopsy. METHODS: We retrospectively included 123 patients diagnosed with IR PC (prostate-specific antigen <20 ng/mL, grade group (GG) 2 or 3, no iT3 on MRI) at MRI-guided biopsy, who underwent RP. Twelve GP4 amount-related parameters were developed, based on GP4 quantification method (absolute, relative to core, or cancer length) and site (overall, targeted, systematic biopsy, or worst specimen). Additionally, we calculated PV×GP4 (prostate volume × GP4 relative to core length in overall biopsy), aiming to represent the total GP4 volume in the prostate. The associations of GP4 with AP (GG ≥ 4, ≥pT3a, or pN1) were investigated. RESULTS: AP was reported in 39 (31.7%) of patients. GP4 relative to cancer length was not associated with AP. Of the 12 parameters, the highest ROC AUC value was seen for GP4 relative to core length in overall biopsy (0.65). an even higher AUC value was noted for PV × GP4 (0.67), with a negative predictive value of 82.8% at the optimal threshold. CONCLUSIONS: The lack of an association of GP4 relative to cancer length with AP, contrasted with the better performance of other parameters, indicates directions for future research on PC risk stratification to accurately identify patients who may not require immediate treatment. Incorporating formulas aimed at GP4 volume assessment may lead to obtaining models with the best discrimination ability.

Patient-reported pain associated with grid-based transperineal magnetic resonance imaging (MRI)/ultrasound (US) software fusion biopsy of the prostate under local anesthesia: a multicenter experience.

Background: Biopsy by transperineal (TP) approach is recommended standard for prostate cancer (PC) diagnosis. To avoid pain, patients undergoing TP biopsy may be offered sedation or general anesthesia. Our aim was to investigate the degree of patient-reported pain for magnetic resonance imaging (MRI)/ultrasound (US) fusion biopsy of the prostate being performed under local anesthesia (LA) and to study for possible factors associated with increased risk of significant pain (SP) in this setting. Methods: In this retrospective observational study, we reviewed data of consecutive patients without a prior diagnosis of PC who underwent MRI/US software fusion biopsy of the prostate under LA with lidocaine at two centers between May 2020 and April 2022, and who reported their periprocedural pain on a Wong-Baker FACES Pain Rating Scale (0-10). We defined SP as reported pain score of 6-10. Patient and procedure characteristics together with SP were studied for interdependencies. Results: A total of 299 patients were included. Median pain score was 2 (interquartile range: 2-4), with SP having been reported by 55 (18.4%) patients. Among patient characteristics, only age demonstrated association with SP [odds ratio (OR), per 10 years =0.53, 95% confidence interval (CI): 0.35-0.80, P=0.003] and patients aged 62 or above were significantly less likely to report SP (OR =0.33, 95% CI: 0.18-0.60, P<0.001). Conclusions: Performing TP MRI/US fusion prostate biopsy under LA is associated with low rates of SP, with the risk being significantly lower in older men. The results of this study can serve as evidence resource for preprocedural counselling in patients especially concerned about the risk of pain.

Validity of the hydrogen ion mobilisation model during haemodialysis with time-dependent dialysate bicarbonate concentrations.

BACKGROUND: The hydrogen ion (H+) mobilisation model has been previously shown to accurately describe blood bicarbonate (HCO3) kinetics during haemodialysis (HD) when the dialysate bicarbonate concentration ([HCO3]) is constant throughout the treatment. This study evaluated the ability of the H+ mobilization model to describe blood HCO3 kinetics during HD treatments with a time-dependent dialysate [HCO3]. METHODS: Data from a recent clinical study where blood [HCO3] was measured at the beginning of and every hour during 4-h treatments in 20 chronic, thrice-weekly HD patients with a constant (Treatment A), decreasing (Treatment B) and increasing (Treatment C) dialysate [HCO3] were evaluated. The H+ mobilization model was used to determine the model parameter (Hm) that provided the best fit of the model to the clinical data using nonlinear regression. A total of 114 HD treatments provided individual estimates of Hm. RESULTS: Mean ± standard deviation estimates of Hm during Treatments A, B and C were 0.153 ± 0.069, 0.180 ± 0.109 and 0.205 ± 0.141 L/min (medians [interquartile ranges] were 0.145 [0.118,0.191], 0.159 [0.112,0.209], 0.169 [0.115,0.236] L/min), respectively; these estimates were not different from each other (p = 0.26). The sum of squared differences between the measured blood [HCO3] and that predicted by the model were not different during Treatments A, B and C (p = 0.50), suggesting a similar degree of model fit to the data. CONCLUSIONS: This study supports the validity of the H+ mobilization model to describe intradialysis blood HCO3 kinetics during HD with a constant Hm value when using a time-dependent dialysate [HCO3].

Incidental Diagnosis of Urothelial Bladder Cancer: Associations with Overall Survival.

BACKGROUND: We investigated whether an incidental diagnosis (ID) of bladder cancer (BC) was associated with improved survival. METHODS: We retrospectively reviewed data of consecutive patients with no prior diagnosis of urothelial cancer who underwent a primary transurethral resection of bladder tumor (pTURBT) between January 2013 and February 2021 and were subsequently diagnosed with urothelial BC. The type of diagnosis (incidental or non-incidental) was identified. Overall, relative, recurrence-free, and progression-free survival rates (OS, RS, RFS, and PFS) after pTURBT were evaluated using the Kaplan-Meier curves and long-rank tests. A multivariable Cox regression model for the overall mortality was developed. RESULTS: A total of 435 patients were enrolled. The median follow-up was 2.7 years. ID cases were more likely to be low-grade (LG) and non-muscle-invasive. ID vs. non-ID was associated with a trend toward an improved 7-year OS (66% vs. 49%, p = 0.092) and a significantly improved 7-year OS, if incidental cases were limited to ultrasound-detected tumors (75% vs. 49%, p = 0.013). ID was associated with improved survival among muscle-invasive BC (MIBC) patients (3-year RS: 97% vs. 23%, p < 0.001), but not among other subgroups stratified according to disease stage or grade. In multivariable analysis, only age, MIBC, and high-grade (HG) cancer demonstrated an association with mortality. PFS and RFS among non-MIBC patients did not differ in regard to the type of diagnosis. CONCLUSIONS: Incidental diagnosis may contribute to an improved survival in BC patients, most probably in the mechanism of the relative downgrading of the disease, including the possible overdiagnosis of LG tumors. Nevertheless, in the subgroup analyses, we noted marked survival benefits in MIBC cases. Further prospective studies are warranted to gain a deeper understanding of the observed associations.

Early efficacy and safety of obinutuzumab with chemotherapy in previously untreated patients with follicular lymphoma: A real-world retrospective report of the Polish Lymphoma Research Group.

BACKGROUND: The first-line obinutuzumab-based immunochemotherapy improves the outcome of patients with follicular lymphoma (FL) compared with rituximab-based regimens. However, infusion-related reactions occur in almost half of patients during the 1st obinutuzumab administration. OBJECTIVES: The study aimed to evaluate the early effectiveness and safety of obinutuzumab-based induction regimens in a real-world setting. MATERIAL AND METHODS: Outcomes of patients diagnosed with FL and treated with obinutuzumab between January 2020 and September 2021 were analyzed. RESULTS: The study group included 143 treatment-naïve patients with FL. The median age was 52 years (range: 28-89 years); 45.1% of patients had a high-risk disease as assessed using the Follicular Lymphoma International Prognostic Index (FLIPI). Induction chemotherapy included: O-CVP (obinutuzumab, cyclophosphamide, vincristine, prednisolone) in 49.0% of patients, O-CHOP (O-CVP plus doxorubicin) in 28.7% and O-BENDA (obinutuzumab, bendamustine) in 22.4%. Complete response (CR) and partial response (PR) rates were 69.9% and 26.5%, respectively. There was no difference in response rates between different regimens (p = 0.309). Maintenance was started in 115 patients (85.2%). In the 1st cycle, obinutuzumab was administered as a single 1000-milligram infusion in 47.9% of patients, whereas in 52.1%, initial infusions were split over 2 days (100 mg/900 mg). Infusion-related reactions were reported only during the 1st administration of obinutuzumab in 9.1% of patients, with a similar incidence in those receiving the total dose on a single day or split over 2 days (p = 0.458). The most common adverse events were hematological. Five patients died from coronavirus disease 2019 (COVID-19). CONCLUSION: The early responses to induction regimens and adverse events profile were similar for every type of induction treatment. The infusion-related reactions were rare and limited to the 1st dose of obinutuzumab.

Urine volume as an estimator of residual renal clearance and urinary removal of solutes in patients undergoing peritoneal dialysis.

In non-anuric patients undergoing peritoneal dialysis (PD), residual kidney function (RKF) is a main contributor to fluid and solute removal and an independent predictor of survival. We investigated if urine volume could be used to estimate renal clearances and removal of urea, creatinine, and phosphorus in PD patients. The observational, cross-sectional study included 93 non-anuric prevalent PD patients undergoing continuous ambulatory PD (CAPD; n = 34) or automated PD (APD; n = 59). Concentrations of urea, creatinine and phosphorus in serum and in 24-h collections of urine volume were measured to calculate weekly residual renal clearance (L/week) and removed solute mass (g/week). Median [interquartile range], 24-h urine output was 560 [330-950] mL and measured GFR (the mean of creatinine and urea clearances) was 3.24 [1.47-5.67] mL/min. For urea, creatinine and phosphorus, residual renal clearance was 20.60 [11.49-35.79], 43.02 [19.13-75.48] and 17.50 [8.34-33.58] L/week, respectively, with no significant differences between CAPD and APD. Urine volume correlated positively with removed solute masses (rho = 0.82, 0.67 and 0.74) and with weekly residual renal clearances (rho = 0.77, 0.62 and 0.72 for urea, creatinine, and phosphorus, respectively, all p < 0.001). Residual renal clearances and urinary mass removal rates for urea, creatinine, and phosphorus correlate strongly with 24-h urine volume suggesting that urine volume could serve as an estimator of typical values of residual solute removal indices in PD patients.

PD-L1-Positive High-Grade Triple-Negative Breast Cancer Patients Respond Better to Standard Neoadjuvant Treatment-A Retrospective Study of PD-L1 Expression in Relation to Different Clinicopathological Parameters.

Triple negative breast cancer (TNBC) is typically a high-grade breast cancer with poorest clinical outcome despite available treatment modalities with chemo-, immuno- and radiotherapy. The status of tumor-infiltrating lymphocytes (TILs) is a prognostic factor closely related to programmed death ligand 1 (PD-L1) expressed on T lymphocytes modulating antitumor immunity. Immune-checkpoint inhibitors (ICI) are showing promising results in a subset of breast cancer patients in both neo- and adjuvant settings. Pathologic complete response (pCR) after neoadjuvant treatment was found to be associated with better prognosis. We analyzed the prognostic and predictive significance of PD-L1 (SP142 assay) immunohistochemical expression on TNBC patients' samples as illustrated by pCR with regard to its relation to treatment regimen, stage, BRCA mutational status and outcome. Furthermore, we analyzed a few other clinicopathological parameters such as age, TILs and proliferation index. The study highlighted a positive role of PD-L1 evaluation for personalized pCR probability assessment. Although considerable research was made on comparison of PD-L1 level in TNBC with different patient parameters, to our best knowledge, the relation of PD-L1 status to pCR while taking treatment regimen and stage into consideration was so far not investigated.

Rituximab and Chemotherapy for Newly Diagnosed Follicular Lymphoma: Real-World Report of Polish Lymphoma Research Group.

INTRODUCTION: Follicular lymphoma (FL) is the most common type of indolent B-cell lymphoma with a favorable prognosis in the majority of patients. The induction treatment is still based on rituximab and chemotherapy, though new anti-CD20 antibody and chemo-free regimen have been recently introduced. The aim of the study was to analyze the management, outcomes, and determinants of prognosis of newly diagnosed patients with FL in real-world experience. METHODS: Data of consecutive patients diagnosed with FL in 5 years period (2011-2015) in three oncohematological centers were reviewed. Variables were compared using Mann-Whitney or χ2 test as appropriate, survival outpoints were calculated using Kaplan-Meier method. RESULTS: One hundred eighty-one patients were included in the study. The median patients' age at diagnosis was 56.6 years. Low histological grade (G1-G2) was found in 62.1% of patients and advanced clinical stage in 77.0% of patients. ECOG 0 performance status was observed in 57.1% of patients. The median follow-up was 5.91 years. Initially, 31.5% of the patients were qualified to watch-and-wait (W&W) strategy, and 84.0% of the whole patients' group received systemic treatment during the observation period. As induction treatment, 53.9% and 41.4% of patients received RCVP and RCHOP regimens, respectively; 39.8% received rituximab maintenance (RM) after first-line therapy. During follow-up, transformation to aggressive lymphoma occurred in 7.2% of patients. Median overall survival (OS) was not achieved, and median progression-free survival (PFS) was 8.28 years (95% CI; 7.35, NA), 19.6% of patients relapsed during 24 months from the start of the treatment (POD24). Median PFS for POD24 group was 1.1 years (95% CI; 0.56, 1.45) with a median OS longer than 8 years. ECOG 0, low PRIMA PI, and no POD24 were found as determinants of longer PFS and OS. CONCLUSIONS: Our data from clinical practice showed that rituximab and chemotherapy is still an effective method of FL treatment resulting in survival more than 8 years from diagnosis in most patients. RCVP protocol followed with RM is a reasonable choice for the first-line therapy especially in low/intermediate group of patients. The prognosis was significantly worse in patients with POD24. Therefore, searching for precise initial clinical and biological markers is warranted and development therapies to improve prognosis of POD24 patients.

The Clinical Features of Incidentally Diagnosed Urothelial Bladder Cancer: A Retrospective Data Analysis.

INTRODUCTION: The aim of this study was to evaluate the prevalence and clinical features of incidental bladder cancer (BC) diagnosis, with special emphasis on possible associations between incidental diagnosis and primary disease stage or grade. METHODS: We retrospectively included 501 consecutive patients who underwent transurethral resection of bladder tumor and were diagnosed with primary urothelial carcinoma of the bladder between January 2013 and February 2021 in a university hospital. The type of diagnosis (incidental or nonincidental), patient baseline characteristics and primary stage and grade were studied for interdependencies. RESULTS: 28.5% of all patients and 19.8% of high grade (HG) BC patients had been diagnosed incidentally, most commonly with ultrasound. Incidental diagnosis was associated with lower primary stage and grade of the disease. Most importantly, on multivariable analysis, which included baseline patient characteristics and type of diagnosis, in the subgroup of HG BC patients, muscle-invasive BC (MIBC) or metastatic disease was three times less likely to be diagnosed incidentally than non-MIBC (odds ratio: 0.31, 95% confidence interval: 0.14-0.71, p = 0.006). CONCLUSIONS: The study is first to demonstrate that incidental diagnosis of HG BC may be surprisingly prevalent and associated with lower rates of muscle invasion or metastatic disease.

Predictors of Clinically Significant Prostate Cancer in Patients with PIRADS Categories 3-5 Undergoing Magnetic Resonance Imaging-Ultrasound Fusion Biopsy of the Prostate.

Prostate biopsy is recommended in cases of positive magnetic resonance imaging (MRI), defined as Prostate Imaging Reporting and Data System (PIRADS) category ≥ 3. However, most men with positive MRIs will not be diagnosed with clinically significant prostate cancer (csPC). Our goal was to evaluate pre-biopsy characteristics that influence the probability of a csPC diagnosis in these patients. We retrospectively analyzed 740 consecutive men with a positive MRI and no prior PC diagnosis who underwent MRI-ultrasound fusion biopsies of the prostate in three centers. csPC detection rates (CDRs) for each PIRADS category were calculated. Patient, disease, and lesion characteristics were studied for interdependencies with the csPC diagnosis. The CDR in patients with PIRADS categories 3, 4, and 5 was 10.5%, 30.7%, and 54.6%, respectively. On both uni- and multivariable regression models, older age, being biopsy-naïve, prostate specific antigen ≥ 10 ng/mL, smaller prostate volume, PIRADS > 3, a larger maximum lesion size, a lesion in the peripheral zone, and a positive digital rectal examination were associated with csPC. In this large, multicenter study, we provide new data regarding CDRs in particular PIRADS categories. In addition, we present several strong predictors that further alter the risk of csPC in MRI-positive patients. Our results could help in refining individual risk assessment, especially in PIRADS 3 patients, in whom the risk of csPC is substantially low.

Changes in Subendocardial Viability Ratio in Traumatic Brain Injury Patients.

Background: Traumatic brain injury (TBI) is often associated with cardiac dysfunction, which is a consequence of the brain-heart cross talk. The subendocardial viability ratio (SEVR) is an estimate of myocardial perfusion. The aim of this study was to analyze changes in the SEVR in patients with severe TBI without previous cardiac diseases. Methods: Adult patients treated for severe TBI with a Glasgow coma score <8 were studied. Pressure waveforms were obtained by a high-fidelity tonometer in the radial artery for SEVR calculation at five time points: immediately after admission to the intensive care unit and 24, 48, 72, and 96 h after admission. SEVRs and other clinically important parameters were analyzed in patients who survived and did not survive after 28 days of treatment, as well as in patients who underwent decompressive craniectomy (DC). Results: A total of 64 patients (16 females and 48 males) aged 18-64 years were included. Fifty patients survived and 14 died. DC was performed in 23 patients. SEVRs decreased 24 h after admission in nonsurvivors (p < 0.05) and after 48 h in survivors (p < 0.01) and its values were significantly lower in nonsurvivors than in survivors at 24, 72, and 96 h from admission (p < 0.05). The SEVR increased following DC (p < 0.05). Conclusions: A decreased SEVR is observed in TBI patients. Surgical decompression increases the SEVR, indicating improvement in coronary microvascular perfusion. The results of our study seem to confirm that brain injury affects myocardium function.

Phosphate clearance in peritoneal dialysis.

In renal failure, hyperphosphatemia is common and correlates with increased mortality making phosphate removal a key priority for dialysis therapy. We investigated phosphate clearance, removal and serum level, and factors associated with phosphate control in patients undergoing continuous ambulatory (CAPD), continuous cyclic (CCPD) and automated (APD) peritoneal dialysis (PD). In 154 prevalent PD patients (mean age 53.2 ± 17.6 year, 59% men, 47% anuric), 196 daily collections of urine and 368 collections of dialysate were evaluated in terms of renal, peritoneal and total (renal plus peritoneal) phosphorus removal (g/week), phosphate and creatinine clearances (L/week) and urea KT/V. Dialytic removal of phosphorus was lower in APD (1.34 ± 0.62 g/week) than in CAPD (1.89 ± 0.73 g/week) and CCPD (1.91 ± 0.63 g/week) patients; concomitantly, serum phosphorus was higher in APD than in CAPD (5.55 ± 1.61 vs. 4.84 ± 1.23 mg/dL; p < 0.05). Peritoneal and total phosphate clearances correlated with peritoneal (rho = 0.93) and total (rho = 0.85) creatinine clearances (p < 0.001) but less with peritoneal and total urea KT/V (rho = 0.60 and rho = 0.65, respectively, p < 0.001). Phosphate removal, clearance and serum levels differed between PD modalities. CAPD was associated with higher peritoneal removal and lower serum level of phosphate than APD.

Association between Biomarkers of Mineral and Bone Metabolism and Removal of Calcium and Phosphate in Hemodialysis.

BACKGROUND: A significant drop of serum phosphate and calcium removal or loading during hemodialysis induce reactions in mineral and bone remodeling that may inversely affect phosphate and calcium removal during dialysis. OBJECTIVES: We aimed to analyze the interdependencies between biomarkers of mineral and bone metabolism and removal of phosphate and calcium during hemodialysis, as this complex relationship is not fully understood. METHODS: Three subsequent hemodialysis sessions during a 1-week treatment cycle with interdialytic periods of 2-2-3 days were monitored in 25 anuric patients. Calcium and phosphate concentrations were measured in serum before, at 1, 2, and 3 h, at the end, and 45 min after each session and in the outlet dialysate every 30 min. Biomarkers associated with mineral and bone metabolism: parathyroid hormone (PTH 1-34 and PTH 1-84), calcitonin, 25(OH)-vitamin D, fetuin-A, osteopontin, osteocalcin 1-43/49, and intact osteocalcin were assayed once in each patient before the midweek hemodialysis session. RESULTS: Post-dialytic and intra-dialytic serum phosphate of midweek hemodialysis session and phosphate mass removed within 1 week correlated positively with serum PTH (0.40 < rho <0.46, p value <0.05). Higher concentration of serum PTH was associated with an increased level of osteocalcin. Pre-dialytic, post-dialytic, average for treatment time and average weekly concentrations of ionized calcium in serum correlated positively with serum osteocalcin. Serum osteocalcin and osteopontin levels were associated with the masses of total and ionized calcium, respectively, removed during 3 hemodialysis sessions. CONCLUSIONS: During hemodialysis, phosphate removal was associated with serum PTH, whereas calcium kinetics was influenced by serum osteocalcin and osteopontin. These results demonstrate that active processes involving biomarkers of mineral and bone metabolism are affected by the phosphate and calcium kinetics already within 4 h hemodialysis sessions.

Anticoagulation in chronic kidney disease patients with atrial fibrillation: old vs new drugs.

In the last two decades a group of novel oral anticoagulants (NOACs) has been developed that directly block the activity of thrombin or activated factor X. No randomized controlled trials have been conducted to verify their efficacy and safety in patients with advanced chronic kidney disease (CKD) and atrial fibrillation. Few studies compared NOACs (dabigatran, rivaroxaban, apixaban, edoxaban) with classic anticoagulants in this unique group, and the results of these analyses remain controversial and inconclusive. Simple extrapolation of recommendations from the general population may be erroneous and lead to an increased risk of complications. Several controlled randomized trials with oral direct anticoagulants in hemodialysis patients are currently underway.

Hemodialysis-induced changes in hematocrit, hemoglobin and total protein: Implications for relative blood volume monitoring.

BACKGROUND: Relative blood volume (RBV) changes during hemodialysis (HD) are typically estimated based on online measurements of hematocrit, hemoglobin or total blood protein. The aim of this study was to assess changes in the above parameters during HD in order to compare the potential differences in the RBV changes estimated by individual methods. METHODS: 25 anuric maintenance HD patients were monitored during a 1-week conventional HD treatment. Blood samples were collected from the arterial dialysis blood line at the beginning and at the end of each HD session. The analysis of blood samples was performed using the hematology analyzer Advia 2120 and clinical chemistry analyzer Advia 1800 (Siemens Healthcare). RESULTS: During the analyzed 30 HD sessions with ultrafiltration in the range 0.7-4.0 L (2.5 ± 0.8 L) hematocrit (HCT) increased by 9.1 ± 7.0% (mean ± SD), hemoglobin (HGB) increased by 10.6 ± 6.3%, total plasma protein (TPP) increased by 15.6 ± 9.5%, total blood protein (TBP) increased by 10.4 ± 5.8%, red blood cell count (RBC) increased by 10.8 ± 7.1%, while mean corpuscular red cell volume (MCV) decreased by 1.5 ± 1.1% (all changes statistically significant, p < 0.001). HGB increased on average by 1.5% more than HCT (p < 0.001). The difference between HGB and TBP increase was insignificant (p = 0.16). CONCLUSIONS: Tracking HGB or TBP can be treated as equivalent for the purpose of estimating RBV changes during HD. Due to the reduction of MCV, the HCT-based estimate of RBV changes may underestimate the actual blood volume changes.

Impact of hemodialysis on cardiovascular system assessed by pulse wave analysis.

Valuable information about cardiovascular system can be derived from the shape of aortic pulse wave being the result of reciprocal interaction between heart and vasculature. Pressure profiles in ascending aorta were obtained from peripheral waveforms recorded non-invasively (SphygmoCor, AtCor Medical, Australia) before, during and after hemodialysis sessions performed after 3-day and 2-day interdialytic intervals in 35 anuric, prevalent hemodialysis patients. Fluid status was assessed by Body Composition Monitor (Fresenius Medical Care, Bad Homburg, Germany) and online hematocrit monitoring device (CritLine, HemaMetrics, Utah). Systolic pressure and ejection duration decreased during dialysis. Augmentation index remained stable at 30 ± 13% throughout hemodialysis session despite the decrease of augmented pressure and pulse height. Subendocardial viability ratio (SEVR) determined after 3-day and 2-day interdialytic intervals increased during the sessions by 43.8 ± 26.6% and 26.1 ± 25.4%, respectively. Hemodialysis performed after 3-day and 2-day interdialytic periods reduced significantly overhydration by 2.4 ± 1.0 L and 1.8 ± 1.2 L and blood volume by 16.3 ± 9.7% and 13.7 ± 8.9%, respectively. Intradialytic increase of SEVR correlated with ultrafiltration rate (R = 0.39, p-value < 0.01), reduction in overhydration (R = -0.57, p-value < 0.001) and blood volume drop (R = -0.38, p-value < 0.01). The strong correlation between the decrease of overhydration during hemodialysis and increase in SEVR confirmed that careful fluid management is crucial for proper cardiac function. Hemodialysis affected cardiovascular system with the parameters derived from pulse-wave-analysis (systolic and augmented pressures, pulse height, ejection duration, SEVR) being significantly different at the end of dialysis from those before the session. Combination of pulse-wave-analysis with the monitoring of overhydration provides a new insight into the impact of hemodialysis on cardiovascular system.

Patient-specific pulse wave propagation model identifies cardiovascular risk characteristics in hemodialysis patients.

Risk of cardiovascular associated death in dialysis patients is the highest among all other co-morbidities. Improving the identification of patients with the highest cardiovascular risk to design an adequate treatment is, therefore, of utmost importance. There are several non-invasive cardiovascular state biomarkers based on the pulse (pressure) wave propagation properties, but their major determinants are not fully understood. In the current study we aimed to provide a framework to precisely dissect the information available in non-invasively recorded pulse wave in hemodialysis patients. Radial pressure wave profiles were recorded before, during and after two independent hemodialysis sessions in 35 anuric prevalent hemodialysis patients and once in a group of 32 healthy volunteers. Each recording was used to estimate six subject-specific parameters of pulse wave propagation model. Pressure profiles were also analyzed using SphygmoCor software (AtCor Medical, Australia) to derive values of already established biomarkers, i.e. augmentation index and sub-endocardial viability ratio (SEVR). Data preprocessing using propensity score matching allowed to compare hemodialysis and healthy groups. Augmentation index remained on average stable at 142 ± 28% during dialysis and had similar values in both considered groups. SEVR, whose pre-dialytic value was on average lower by 12% compared to healthy participants, was improved by hemodialysis, with post-dialytic values indistinguishable from those in healthy population (p-value > 0.2). The model, however, identified that the patients on hemodialysis had significantly increased stiffness of both large and small arteries compared to healthy counterparts (> 60% before dialysis with p-value < 0.05 or borderline) and that it was only transiently decreased during hemodialysis session. Additionally, correlation-based clustering revealed that augmentation index reflects the shape of heart ejection profile and SEVR is associated with stiffness of larger arteries. Patient-specific pulse wave propagation modeling coupled with radial pressure profile recording correctly identified increased arterial stiffness in hemodialysis patients, while regular pulse wave analysis based biomarkers failed to show significant differences. Further model testing in larger populations and investigating other biomarkers are needed to confirm these findings.

Correction: Quantification of Dialytic Removal and Extracellular Calcium Mass Balance during a Weekly Cycle of Hemodialysis.

[This corrects the article DOI: 10.1371/journal.pone.0153285.].