Blood Volume Research Articles

NIMG-36. PERFUSION, DIFFUSION, AND ANATOMICAL MRI BIOMARKERS FOR ASSESSING HISTOLOGICALLY-CONFIRMED MALIGNANT TRANSFORMATION IN MOLECULAR SUBTYPES OF IDH-MUTANT GLIOMAS

Abstract BACKGROUND Isocitrate dehydrogenase-mutant (IDHm) gliomas often initially present as low-grade (grade 2) gliomas but are expected to later progress into more aggressive higher-grade (grade 3-4) gliomas through malignant transformation (MT). MT is often determined non-invasively by emergence of contrast-enhancement on post-contrast T1-weighted magnetic resonance imaging (MRI), but contrast-enhancement is an imperfect surrogate for histologically-confirmed MT. This study explored perfusion, diffusion, and anatomical MRI biomarkers besides contrast-enhancement to study histologically-confirmed MT in IDHm 1p/19q-intact astrocytomas (IDHm-A) and IDHm 1p/19q-co-deleted oligodendrogliomas (IDHm-O). METHODS N=64 patients with initial histopathological grade 2 IDH-mutant glioma diagnosis who underwent repeated tissue sampling and were classified as histologically-confirmed MT (n=35) or non-MT (n=29) were retrospectively studied. Pre-surgical anatomical MRI (n=64) and, if available, diffusion-weighted imaging (n=61) and dynamic susceptibility contrast perfusion MRI (n=53) were analyzed. Tumor volumes of interest were segmented on the whole T2/FLAIR-hyperintense tumor. Measurable contrast enhancement (>1000mm3), tumor volume, sphericity, median apparent diffusion coefficient (ADC), and normalized relative cerebral blood volume (nrCBV) were compared between MT vs. non-MT IDHm-A and IDHm-O. RESULTS 81% of contrast-enhancing IDHm-A and 100% of contrast-enhancing IDHm-O underwent MT, while 41% of MT IDHm-A and 62% of MT IDHm-O were non-enhancing. Tumor volumes were significantly larger in the MT vs. non-MT groups for both IDHm-A (P=0.02) and IDHm-O (P=0.04). Whole tumor nrCBV was significantly higher (P=0.002), whole tumor ADC trended lower (P=0.06), and non-enhancing tumor sphericity was significantly lower (P=0.03) in MT vs. non-MT IDHm-A. There were no significant differences in ADC, nrCBV, nor sphericity when comparing MT vs. non-MT IDHm-O (P>0.05). CONCLUSIONS Many MT IDHm-gliomas remain non-enhancing. Tumor volumes can determine MT for both IDHm-A and IDHm-O. Diffusion and perfusion MRI show differences for MT in IDHm-A but not IDHm-O, which may reflect the different tumor biology of these IDHm molecular subtypes and their need for separate imaging biomarkers.

NIMG-23. A NOVEL APPROACH TO PERFUSION MRI STUDIES IN BRAIN TUMOR PATIENTS USING ENDOGENOUS DEOXYHEMOGLOBIN AS A CONTRAST AGENT: A PROOF-OF-CONCEPT STUDY

Abstract BACKGROUND Assessment of resting perfusion in brain tumors is clinically relevant and relies on dynamic susceptibility contrast magnetic resonance imaging using gadolinium contrast. Preliminary studies have introduced the use of controlled hemoglobin desaturation by means of a transient hypoxic stimulus during echo-planar imaging(EPI) as a surrogate for gadolinium for resting perfusion assessment in healthy subjects. In this proof of concept study, we investigated whether this approach is feasible in brain tumors and warrant further validation. METHODS A computer controlled gas blender was used to induce transient and standardized hypoxic stimulus in isocapnic conditions during EPI acquisition in a heterogenous cohort of tumor patients. The induced blood-oxygen-level-dependent(BOLD) signal changes determined by transit of a bolus of deoxygenated blood in the brain vasculature were used as a surrogate of gadolinium to calculate cerebral blood volume(CBV), cerebral blood flow(CBF) and mean transit time(MTT) using a global arterial input functions obtained through the BOLD signal measured over the middle cerebral artery as previously described by Poublanc et al. Perfusion parameters were calculated in the whole-brain voxel-by-voxel and in automatically segmented region of interest(ROI) using SPM, AFNI, Verbena softwares and MATLAB in-house written scripts. RESULTS Nine patients were included. MTT, rCBV, rCBF were calculated voxel-per-voxel. Obtained maps were overlayed on the co-registered T1 MRI scans and compared to T1CE and FLAIR to identify perfusion patterns in tumor ROIs (contrast enhancement, edema, necrosis). The deoxy-hemoglobin BOLD MRI perfusion were compared to clinical DSC-MRI when available and showed high qualitative agreement. CONCLUSION Transient and precise hemoglobin desaturation by controlled hypoxic gas modulation is safe and repeatable in brain tumor patients. The induced BOLD signal change allows measurement of resting perfusion, which qualitatively closely mimic gadolinium perfusion in different brain tumors. Deoxyhemoglobin-based perfusion warrant further quantitative validation against gadolinium in a larger cohort of heterogenous tumor patients.

NIMG-37. “SYNTHETIC” PERFUSION MRI WITH ADJUSTABLE ACQUISITION PARAMETERS IN BRAIN TUMORS USING DYNAMIC SPIN-AND-GRADIENT-ECHO ECHOPLANAR IMAGING

Abstract INTRODUCTION Dynamic susceptibility contrast (DSC) perfusion MRI can assess normalized relative cerebral blood volume (nrCBV) and percentage of signal recovery (PSR) in brain tumors, which can aid in differential diagnosis, molecular profiling, and identification of disease progression. However, CBV-optimized and PSR-optimized protocols differ in terms of acquisition parameters. Additionally, DSC dependency on acquisition parameters limits the universalizability of diagnostic cutoffs for nrCBV and PSR across institutions and scanners. This study aims to generate “synthetic” DSC datasets with adjustable synthetic acquisition parameters using dynamic spin-and-gradient-echo echoplanar imaging (dynamic SAGE-EPI) to: 1) simultaneously generate nrCBV and PSR with optimal acquisition parameters, 2) compare DSC datasets with heterogeneous external cohorts. METHODS Thirty-eight patients with contrast-enhancing brain tumors were prospectively imaged with dynamic SAGE-EPI during a non-preloaded single-dose contrast injection. Multiple synthetic DSC datasets with desired pulse sequence parameters were generated using the Bloch equations applied to the dual-echo gradient-echo (GE) data extracted from dynamic SAGE-EPI datasets, with or without optional preload simulation. For each patient, synthetic protocols were set to match guideline-compliant CBV-optimized protocols, PSR-optimized protocols, and protocols used in external cohorts from the literature, for comparison. RESULTS Dynamic SAGE-EPI allowed for simultaneous generation of CBV-optimized and PSR-optimized DSC datasets with a single contrast injection. Conversely, suboptimal PSR computation from guideline-compliant CBV-optimized protocols resulted in rank variations within the cohort (Spearman’s ρ=0.83-0.89, i.e. 31%-21% rank variation). Treatment-naïve glioblastoma exhibited lower parameter-matched PSR compared to the external cohorts of treatment-naïve primary CNS lymphomas (PCNSL) (p<0.0001), supporting a role of synthetic DSC for multicenter comparisons. CONCLUSIONS Dynamic SAGE-EPI allows for simultaneous generation of CBV-optimized and PSR-optimized DSC data with a single injection, facilitating use of a single perfusion protocol for all DSC applications. This approach may also be useful for comparisons of perfusion parameters across heterogeneous multicenter datasets.

Analytical performance of a point-of-care CBC hematology analyzer, including a 5-part differential: A prospective study to evaluate a microfluidic flow cytometry–based analyzer in waived settings

Abstract Objectives A microfluidic flow cytometer–based point-of-care (POC) analyzer was validated against an in-laboratory hematology analyzer (Sysmex XN Automated Hematology System). Concordance on a full complete blood cell count (CBC) with 5-part differential, as performed by operators with no prior clinical laboratory experience, was evaluated. Methods We prospectively collected 376 venous blood specimens (376) from individuals with self-reported medical conditions and from apparently healthy individuals. Forty-six additional remnant specimens were acquired to ensure coverage of analytic measuring ranges. Parallel testing was performed, with up to 7 hours between testing on the POC and Sysmex XN analyzers. Results Regression analysis resulted in r values of 0.998 to 0.932 for all parameters of a 5-part differential CBC other than basophils (0.709). The mean percentage bias from the reference method, inclusive of the upper and lower reporting limits, was less than 2% for parameters other than lymphocytes (–6.4%), monocytes (25.9%), eosinophils (12.2%), and basophils (–15%). Overall agreement on abnormal flagging was 93.3%. Conclusions The Cito CBC microflow cytometer (CytoChip Inc) provides a CBC with a 5-part differential with accuracy, precision, and abnormal flagging equivalent to a moderate-complexity hematology analyzer. It has the key features required of a POC device that can be operated in a waived setting: minimum space requirements, rapid results, single-action measurement (no sample processing or dilution), ease of use, and minimal blood volume.

Myocardial Posttranscriptional Landscape in Peripartum Cardiomyopathy

BACKGROUND: Pregnancy imposes significant cardiovascular adaptations, including progressive increases in plasma volume and cardiac output. For most women, this physiological adaptation resolves at the end of pregnancy, but some women develop pathological dilatation and ultimately heart failure late in pregnancy or in the postpartum period, manifesting as peripartum cardiomyopathy (PPCM). Despite the mortality risk of this form of heart failure, the molecular mechanisms underlying PPCM have not been extensively examined in human hearts. METHODs: Protein and metabolite profiles from left ventricular tissue of end-stage PPCM patients (N=6–7) were compared with dilated cardiomyopathy (DCM; N=5–6) and nonfailing donors (N=7–18) using unbiased quantitative mass spectrometry. All samples were derived from the Sydney Heart Bank. Data are available via ProteomeXchange with identifier PXD055986. Differential protein expression and metabolite abundance and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. RESULTS: Proteomic analysis identified 2 proteins, SBSPON (somatomedin B and thrombospondin type 1 domain-containing protein precursor) and TNS3 (tensin 3), that were uniquely downregulated in PPCM. SBSPON, an extracellular matrix protein, and TNS3, involved in actin remodeling and cell signaling, may contribute to impaired tissue remodeling and fibrosis in PPCM. Metabolomic analysis revealed elevated levels of homogentisate and deoxycholate and reduced levels of lactate and alanine in PPCM, indicating disrupted metabolic pathways and glucose utilization. Both PPCM and DCM shared pathways related to inflammation, immune responses, and signal transduction. However, thyroid hormone signaling was notably reduced in PPCM, affecting contractility and calcium handling through altered expression of PLN (phospholamban) and Sarcoendoplasmic Reticulum Calcium ATPase (SERCA). Enhanced endoplasmic reticulum stress and altered endocytosis pathways in PPCM suggested additional mechanisms of energy metabolism disruption. CONCLUSIONS: The present study reveals unique posttranslational molecular features of the PPCM myocardium, which mediates cellular and metabolic remodeling, and holds promise as potential targets for therapeutic intervention.

Application of a large wall electric probe (LWEP) for plasma and ambient gas studies

Abstract The operation of a large wall electric probe (LWEP) is analyzed, where the probe surface area in contact with the plasma is only a few times smaller than the area of the plasma boundaries. Compared to a small standard Langmuir probe (SLP), the LWEP may have significantly greater resolution and sensitivity, but could substantially perturb the plasma and distort the measured properties. A target application for the LWEP is where the sensitivity of the measurement is critical, but the effects of the plasma perturbation is minimal. A specific case where a LWEP may outperform a SLP is the measurement of a nonlocal electron distribution function at energies of electron free diffusion, that is, at energies significantly exceeding thermal electron energies, in order to obtain information about the parameters of the plasma or ambient gas. Examination of the LWEP analysis process has revealed that, depending on the plasma volume and probe configurations, it may be necessary to measure either the first or second derivatives of the probe current with respect to the probe potential to derive the energetic part of the electron energy distribution function.

Marked hemoglobin mass expansion and plasma volume contraction in Sherpas acclimatizing to 5,400 m altitude

In lowlanders, high altitude (HA) acclimatization induces hemoconcentration by reducing plasma volume (PV) and increasing total hemoglobin mass (Hbmass). Conversely, Tibetan highlanders living at HA are reported to have a similar hemoglobin concentration ([Hb]) as lowlanders near sea level and we investigated whether this reflects alterations in the PV or the Hbmass response to HA. Baseline assessment of PV and Hbmass was performed by carbon monoxide rebreathing at low altitude (~1,400 m) in Sherpas (an ethnic group of Tibetans living in Nepal) and native lowlanders. Participants then ascended to the Everest Base Camp (5,400 m), where further measurements were performed after ~2 days (EBC 1) and ~6 weeks (EBC 2). While on EBC 1 an increase in [Hb] was observed in lowlanders (p=0.004), but not in Sherpas (p=0.179), marked increases in [Hb] were observed in both groups on EBC 2 (p<0.001). On EBC 1, Hbmass (Sherpas, p=0.393; lowlanders, p=0.123) and PV (Sherpas, p=0.348; lowlanders, p=0.172) were not different from baseline in either group, whilst circulating erythropoietin was increased in both groups (p<0.001). On EBC 2, large increases in Hbmass and reductions in PV were observed along with elevated circulating erythropoietin in both groups (all p<0.002). Neither the increases in erythropoietin on EBC 1 (p=0.846) or EBC 2 (p=0.564), nor the expansion of Hbmass (p=0.771) or reduction in PV (p=0.099) on EBC 2 differed between the groups. We conclude that the hematological response of Sherpas to extended exposure to very high altitude does not fundamentally differ from that of native lowlanders.

Mobilization and Apheresis Collection Strategies to Reduce Platelet Loss in G‐CSF Mobilized Healthy Adult Donors

ABSTRACTGranulocyte‐colony stimulating factor (G‐CSF) mobilizes hematopoietic progenitor cells (HPC) into the peripheral blood. Donor peripheral blood platelet loss has been observed during both G‐CSF mobilization and apheresis collection. This study evaluates two strategies to reduce donor platelet loss, preserve product CD34+ cell yield and collection efficiency and increase volume of whole blood (WB) processed. One hundred and two adults healthy donors were mobilized with either standard dose G‐CSF (9.5–12 mcg/kg/day × 4 days) or lower dose G‐CSF (7.5–10 mcg/kg/day × 4 days) according to their pre‐mobilization platelet count. Apheresis centrifugal force was adjusted by lowering the packing factor (PF) setting on the apheresis instrument. Between‐group differences were observed in absolute donor platelet loss (p = 0.04) favoring lower G‐CSF dosing, while percent donor platelet loss trended towards significance (p = 0.10). Lowering PF from the manufacturer's default of 4.5 to 4.0 demonstrated between‐group differences in absolute donor platelet loss (p < 0.05), percent donor platelet loss (p < 0.001), and apheresis product platelet content (p < 0.001). No differences were observed in the product CD34+ cell content and CD34+ cell collection efficiency when PF was reduced to 4.0. Additionally, a higher volume of WB could be processed due to reduced donor platelet loss. Together, these two strategies may mitigate the risk of cumulative platelet loss in G‐CSF mobilized healthy donors undergoing apheresis collection, thereby increasing the likelihood of completing the target total blood volume to be processed while maintaining donor safety.

Absolute blood volume and long-term survival in chronic hemodialysis patients

Absolute blood volume and long-term survival in chronic hemodialysis patients

Recognition and Management of Postpartum Hemorrhage

Abstract Postpartum hemorrhage (PPH) is an obstetric emergency and refers to excessive blood loss after birth. Loss of blood volume and oxygen-carrying capacity may lead to maternal hypovolemia and hypotension resulting in tissue hypoxia, the onset of anaerobic metabolism, and multiorgan failure. If timely and appropriate action is not taken, cardiac arrest and maternal death may occur. If the amount of blood loss exceeds 500 mL following a vaginal birth or 1000 mL during or following a cesarean section, it is termed PPH. Similar to any other surgical hemorrhage, PPH is classified into primary PPH (occurs within 24 hours of birth) or secondary PPH (between 24 hours and 12 weeks postpartum). PPH is a major contributor to maternal deaths worldwide, and it is estimated that a person dies because of PPH approximately every 5 minutes. Therefore, measures should be directed at prevention and early detection of PPH with prompt management. The prevalence of PPH varies globally and is influenced by location, socioeconomic factors, and the availability and quality of health care. The World Health Organization reported that PPH accounts for a quarter of global maternal deaths. The Mothers and Babies Reducing Risks through Audits and Confidential Enquiries report from the United Kingdom (2023) highlighted that despite rare mortality due to hemorrhage, the number of people dying of obstetric hemorrhage is not decreasing, particularly among people with abnormally invasive placentation. Additionally, substandard care was found to be responsible for more than 50% of deaths due to PPH in the United Kingdom. Therefore, it is vital that adequate healthcare infrastructure, trained and competent healthcare professionals, and immediate access to resources, interventions, and multidisciplinary teams are essential both in well-resourced and resource-restrained healthcare systems. Healthcare professionals must identify the potential risk factors for PPH and initiate preventive measures whenever possible. Additionally, they must respond swiftly if PPH occurs and ensure a multidisciplinary, multilayered approach for a synchronized response to optimize outcomes. This review article emphasizes the etiopathogenesis, diagnosis, and management of PPH based on current scientific evidence as well as international best practice recommendations.

Microvascular insulin resistance with enhanced muscle glucose disposal in CD36 deficiency.

Microvascular dysfunction contributes to insulin resistance. CD36, a fatty acid transporter and modulator of insulin signalling, is abundant in microvascular endothelial cells. Humans carrying the minor allele (G) of CD36 coding variant rs3211938 have 50% reduced CD36 expression and show endothelial dysfunction. We aimed to determine whether G allele carriers have microvascular resistance to insulin and, if so, how this affects glucose disposal. Our multi-disciplinary approach included hyperinsulinaemic-euglycaemic clamps in Cd36-/- and wild-type mice, and in individuals with 50% CD36 deficiency, together with control counterparts, in addition to primary human-derived microvascular endothelial cells with/without CD36 depletion. Insulin clamps showed that Cd36-/- mice have enhanced insulin-stimulated glucose disposal but reduced vascular compliance and capillary perfusion. Intravital microscopy of the gastrocnemius showed unaltered transcapillary insulin flux. CD36-deficient humans had better insulin-stimulated glucose disposal but insulin-unresponsive microvascular blood volume (MBV). Human microvascular cells depleted of CD36 showed impaired insulin activation of Akt, endothelial NO synthase and NO generation. Thus, in CD36 deficiency, microvascular insulin resistance paradoxically associated with enhanced insulin sensitivity of glucose disposal. CD36 deficiency was previously shown to reduce muscle/heart fatty acid uptake, whereas here we showed that it reduced vascular compliance and the ability of insulin to increase MBV for optimising glucose and oxygen delivery. The muscle and heart respond to these energy challenges by transcriptional remodelling priming the tissue for insulin-stimulated glycolytic flux. Reduced oxygen delivery activating hypoxia-induced factors, endothelial release of growth factors or small intracellular vesicles might mediate this adaptation. Targeting NO bioavailability in CD36 deficiency could benefit the microvasculature and muscle/heart metabolism. Clinicaltrials.gov NCT03012386 DATA AVAILABILITY: The RNAseq data generated in this study have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/ ) under accession code GSE235988 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE235988 ).

A Comparative Analysis of Intravenous Clonidine and Dexmedetomidine for Hemodynamic Stability and intraoperative bleeding in Lumbar Spine Surgeries

Lumbar spine surgeries are complex procedures often associated with challenges in maintaining hemodynamic stability and controlling intraoperative bleeding, which are crucial for optimizing patient outcomes. Clonidine and dexmedetomidine both are α2-adrenergic agonists with sedative and analgesic properties, known for their potential to attenuate sympathetic responses and stabilize hemodynamics. However, their comparative efficacy in lumbar spine surgeries remains underexplored. METHODOLOGY This study was carried out in 40 patients, ASA grade1 and 2, undergoing lumbar spinal instrumentation requiring laminectomy. The patients were randomly allocated into two groups (20 each) using the computer generated random number table. Group C received 2 µg/kg of clonidine diluted in 10 ml of normal saline, given slowly intravenous infusion over 10 min before induction of general anaesthesia. Group D received 1 µg/kg of dexmedetomidine diluted in 10 ml normal saline, given slow intravenous infusion over 10 minutes before induction of general anaesthesia. Heart rate, systolic, diastolic, and mean arterial pressure were monitored before intubation as the baseline and after intubation, 15, 30, and 60 minutes after starting the surgery, and after extubation. The amount of intraoperative blood loss was estimated based on the volume of blood in the suction bottle and the number of the blood-soaked gauze pads (20 mL for a completely blood-soaked gauze and 50 mL for a completely blood-soaked long gauze). OBSERVATION No statistically significant difference was found on comparing the two drugs in terms of Baseline characteristics, Mean Arterial Pressure and the amount of blood loss. However Dexmedetomidine group had a higher reduction in Heart Rate as compared to the Clonidine Group. CONCLUSION In conclusion, both the alpha2 agonist drugs; intravenous clonidine and dexmedetomidine represent valuable options for achieving stable hemodynamics as well as decreases the intraoperative surgical bleeding in lumbar spine surgeries. Total opioid requirements for intraoperative and rescue analgesia in postoperative period were decreased in both the groups.

Consumption of a Branched-Chain Amino Acids-Containing Sports Beverage During 21 km of Running Reduces Dehydration, Lowers Muscle Damage, and Prevents a Decline in Lower Limb Strength

Objectives: The purpose of this study was to examine the acute effects of branched-chain amino acids (BCAAs)-containing electrolyte beverage (AE) on water–electrolyte balance, muscle damage, time to finish the final 5 km, and muscle strength compared to a standard commercially available carbohydrate–electrolyte sports beverage (CE), pure water (W), and no rehydration (N). Methods: Fourteen trained male participants (20 ± 2 years old) completed four randomized 21 km running trials. The participants were instructed to consume their drink (150 mL W, 150 mL CE, or 150 mL AE) or no rehydration (N) at 5 km, 10 km, and 15 km. Body mass and muscle strength were assessed, and blood samples were collected before and after exercise. Perceptual scales were administered during and after running. Blood electrolyte levels (sodium, potassium, and chloride) and creatine kinase (CK) concentration were analyzed. Results: The change in plasma volume with AE was significantly smaller than that with N (p < 0.05). Consuming AE maintained the best potassium balance (p < 0.05). Twenty-four hours after exercise, serum CK concentrations significantly elevated in N, W, and CE (p < 0.05), but did not reach statistical significance in the AE group (p > 0.05). Compared to N, consuming AE resulted in significantly less soreness 24 h after exercise (p < 0.05). There was no difference in time to finish the final 5 km (p > 0.05). Maximal voluntary isometric force output was significantly lower after exercise with N and W (p < 0.05) but not with CE or AE (p > 0.05). Conclusions: Consuming a BCAAs-containing sports beverage during a 21 km run can help reduce dehydration, maintain potassium balance, lower muscle damage, and prevent the decline in lower limb strength after 21 km running.

Elevated Perspectives: Unraveling Cardiovascular Dynamics in High-Altitude Realms.

High-altitude regions pose distinctive challenges for cardiovascular health because of decreased oxygen levels, reduced barometric pressure, and colder temperatures. Approximately 82 million people live above 2400 meters, while over 100 million people visit these heights annually. Individuals ascending rapidly or those with pre-existing cardiovascular conditions are particularly vulnerable to altitude-related illnesses, including Acute Mountain Sickness (AMS) and Chronic Mountain Sickness (CMS). The cardiovascular system struggles to adapt to hypoxic stress, which can lead to arrhythmias, systemic hypertension, and right ventricular failure. Pathophysiologically, high-altitude exposure triggers immediate increases in cardiac output and heart rate, often due to enhanced sympathetic activity. Over time, acclimatisation involves complex changes, such as reduced stroke volume and increased blood volume. The pulmonary vasculature also undergoes significant alterations, including hypoxic pulmonary vasoconstriction and vascular remodelling, contributing to conditions, like pulmonary hypertension and high-altitude pulmonary edema. Genetic adaptations in populations living at high altitudes, such as gene variations linked to hypoxia response, further influence these physiological processes. Regarding cardiovascular disease risk, stable coronary artery disease patients generally do not face significant adverse outcomes at altitudes up to 3500 meters. However, those with unstable angina or recent cardiac interventions should avoid high-altitude exposure to prevent exacerbation. Remarkably, high-altitude living correlates with reduced cardiovascular mortality rates, possibly due to improved air quality and hypoxia-induced adaptations. Additionally, there is a higher incidence of congenital heart disease among children born at high altitudes, highlighting the profound impact of hypoxia on heart development. Understanding these dynamics is crucial for managing risks and improving health outcomes in high-altitude environments.

Associations of pulmonary microvascular blood volume with per cent emphysema and CT emphysema subtypes in the community: the MESA Lung study

BackgroundPulmonary microvasculature alterations are implicated in emphysema pathogenesis, but the association between pulmonary microvascular blood volume (PMBV) and emphysema has not been directly assessed at scale, and prior studies have...

In-hospital bioimpedance-derived total body water predicts short-term cardiovascular mortality and re-hospitalizations in acute decompensated heart failure patients.

Hospital re-admissions in heart failure (HF) patients are mostly caused by an acute exacerbation of their chronic congestion. Bioimpedance analysis (BIA) has emerged as a promising non-invasive method to assess the volume status in HF. However, its correlation with clinically assessed volume status and its prognostic value in the acute intra-hospital setting remains uncertain. In this single-center observational study, patients (n = 49) admitted to the cardiology ward for acute decompensated HF (ADHF) underwent a daily BIA-derived volume status assessment. Median hospital stay was 7 (4-10) days. Twenty patients (40%) reached the composite endpoint of cardiovascular mortality or re-hospitalization for HF over 6months. Patients at discharge displayed improved NYHA class, lower body weight, plasma and blood volume, as well as lower NT-proBNP levels compared to the admission. Compared to patients with total body water (TBW) less than or equal to that predicted by body weight, those with higher relative TBW levels had elevated NT-proBNP and E/e´ (both p < 0.05) at discharge. In the Cox multivariate regression analysis, the BIA-derived delta TBW between admission and discharge showed a 23% risk reduction for each unit increase (HR = 0.776; CI 0.67-0.89; p = 0.0006). In line with this finding, TBW at admission had the highest prediction importance of the combined endpoint for a subgroup of high-risk HF patients (n = 35) in a neural network analysis. In ADHF patients, BIA-derived TBW is associated with the increased risk of HF hospitalization or cardiovascular death over 6months. The role of BIA for prognostic stratification merits further investigation.

The safety of cell saver washing all shed mediastinal blood before re-transfusing it to the patient.

Cardiotomy suction blood is used in cardiopulmonary bypass (CPB) surgery to maintain blood volume in the CPB system, although it is known to contain micro emboli, cytokines and free plasma hemoglobin. Our aim was to investigate whether cell saver washing the cardiotomy suction blood before re-transfusing it is safe. This is a retrospective study of 1671 elective coronary artery bypass patients, 209 of whom had their pericardial blood processed in a cell saver (Ce-S group). PS matching was performed with patients who had their pericardial blood returned back to the CPB-system by the cardiotomy suction (Ca-S group). Perioperative transfusion requirements, surgical outcome, postoperative lab data and mortality were then compared. There were no differences in baseline characteristics or EuroSCORE between the groups. The number of patients requiring transfusions did not differ, but the patients in the Ca-S group received more platelets (0.34 ± 1.0 vs 0.16 ± 0.7 units, p = .03) than in the Ce-S group. CRP (c-reactive protein) levels at day 2 and 4 were higher in the Ca-S group (174.8 ± 67.2 and 148.9 ± 74.3mg/L vs 160.1 ± 64.6 and 125.9 ± 67.2mg/L, p = .03, p = .002) and so were ASAT (aspartate aminotransferase) levels (0.97 ± 0.8 vs 0.81 ± 0.6μkat/L, p = .03). Mortality, postoperative ventilation time, stroke, mediastinal infections and length of stay in the ICU were the same in both groups. In this retrospective study of patients undergoing elective CABG surgery, washing the cardiotomy suction blood before re-transfusion was not associated with higher risk of allogenic blood transfusion, postoperative stroke, mediastinal infections, or 30- and 365-days mortality. LU EPN 2016/4.

FLIP: a novel method for patient-specific dose quantification in circulating blood in large vessels during proton or photon external beam radiotherapy treatments.

To provide a novel and personalized method (FLIP, FLowandIrradiation Personalized) using patient-specific circulating blood flows and individualized time-dependent irradiation distributions, to quantify the dose delivered to blood in large vessels during proton or photon external beam radiotherapy. Patient-specific data were obtained from ten cancer patients undergoing radiotherapy, including the blood velocity field in large vessels and the temporal irradiation scheme using photons or protons. The large vessels and the corresponding blood flow velocities are obtained from phase-contrast MRI sequences. The blood dose is obtained discretizing the fluid into individual blood particles (BPs). A Lagrangian approach was applied to simulate the BPs trajectories along the vascular velocity field flowlines. Beam delivery dynamics was obtained from beam delivery machine measurements. The whole irradiation sequence is split into a sequence of successive irradiation elements, each one with its constant dose rate, as well as its corresponding initial and final time. Calculating the dose rate and knowing the spatiotemporal distribution of BPs, the dose is computed by accumulating the energy received by each BP as the time-dependent irradiation beams take place during the treatment. Blood Dose Volume Histograms (DVHs) from proton therapy and photon radiotherapy (RT) patients were assessed. The irradiation times distribution is obtained for BPs in both modalities. Two dosimetric parameters are presented: (i) D3%, representing the minimum dose received by the 3% of BPs receiving the highest doses, and (ii) V0.5Gy, denoting the blood volume percentage that has received at least 0.5 Gy. A novel methodology is proposed for quantifying the circulating blood dose along large vessels. This methodology involves the use of patient-specific vasculature, blood flow velocity field, and dose delivery dynamics recovered from the irradiation machine. Relevant parameters that affect the dose received, as the distance between large vessels and CTV, are identified.

Vasodilatory shock: a review of pathophysiology and vasopressor therapy

Vasodilatory shock is characterised by a global loss of vasomotor tone, leading to maldistribution of blood volume, low systemic arterial pressure and hypoperfusion. This syndrome can be caused by sepsis, anaphylaxis and a wide range of other aetiologies. This review article explores the pathophysiology of vasodilatory shock, including well-understood mechanisms and emerging avenues of future investigation. Options for vasopressor therapy are reviewed, including evidence from preclinical canine models, small animal clinical research, large human clinical trials and the Surviving Sepsis Campaign. Recommendations for rational vasopressor choice are extrapolated from this evidence. Future directions include the development of novel vasoactive agents, clinical data comparing the safety and effectiveness of vasopressors in small animals and the development of a veterinary-specific consensus statement guiding best practices for the treatment of vasodilatory shock.

Plasmapheresis for extracorporeal membrane oxygenation (ECMO)-induced hemolysis in infants

Background: Intravascular hemolysis is a known complication of extracorporeal membrane oxygenation (ECMO). Characterized by elevated plasma-free hemoglobin (PFH), intravascular hemolysis is associated with cytotoxic effects leading to renal replacement therapy (RRT), longer ECMO runs and mortality. Therapeutic plasma exchange (TPE) in tandem with ECMO was described as a therapy for various pathologic conditions, but there are no ELSO guidelines for the treatment of ECMO-induced hemolysis. We describe the use of TPE in the management of severe ECMO-induced hemolysis. Methods: Two term neonates receiving veno-arterial (VA) ECMO developed severe PFH, with peak values over 500 mg/dL. TPE was performed in tandem with the ECMO circuit. Packed red cells were used to prime the TPE circuit, and citrate anticoagulation was added to establish the interface, which could not be achieved with existing heparin in the ECMO circuit. Therapy was completed with saline solution as a decoy for citrate, to avoid hypocalcemia and intracranial bleeding. Plasma volume was replaced by fresh frozen plasma (FFP). Results: In one patient PFH fell to 120 mg/dL, but rebounded to close to 500 mg/dL, only to stabilize between 210 and 300 mg/dL after the second TPE. He was liberated from ECMO, but could not survive a respiratory decompensation. The other patient’s PFH improved to 360 mg/dL after one TPE and continued to decline to 120 mg/dL over the ensuing days. Despite that improvement, care was withdrawn. Conclusion: TPE is effective in decreasing the burden of PFH, is well tolerated in tandem with ECMO, and a database of infants with ECMO-induced hemolysis needs to be created to assess the current practice, and establish clinical guidelines for its most appropriate therapy.