scholarly journals Compressed vessels bias red blood cell partitioning at bifurcations in a hematocrit-dependent manner: Implications in tumor blood flow

2021 ◽  
Vol 118 (25) ◽  
pp. e2025236118
Author(s):  
Romain Enjalbert ◽  
David Hardman ◽  
Timm Krüger ◽  
Miguel O. Bernabeu

The tumor microenvironment is abnormal and associated with tumor tissue hypoxia, immunosuppression, and poor response to treatment. One important abnormality present in tumors is vessel compression. Vessel decompression has been shown to increase survival rates in animal models via enhanced and more homogeneous oxygenation. However, our knowledge of the biophysical mechanisms linking tumor decompression to improved tumor oxygenation is limited. In this study, we propose a computational model to investigate the impact of vessel compression on red blood cell (RBC) dynamics in tumor vascular networks. Our results demonstrate that vessel compression can alter RBC partitioning at bifurcations in a hematocrit-dependent and flow rate–independent manner. We identify RBC focusing due to cross-streamline migration as the mechanism responsible and characterize the spatiotemporal recovery dynamics controlling downstream partitioning. Based on this knowledge, we formulate a reduced-order model that will help future research to elucidate how these effects propagate at a whole vascular network level. These findings contribute to the mechanistic understanding of hemodilution in tumor vascular networks and oxygen homogenization following pharmacological solid tumor decompression.

2020 ◽  
Author(s):  
Romain Enjalbert ◽  
David Hardman ◽  
Timm Krüger ◽  
Miguel O. Bernabeu

AbstractThe tumour microenvironment is abnormal and associated with tumour tissue hypoxia, immunosuppression, and poor response to treatment. One important abnormality present in tumours is vessel compression. Vessel decompression has been shown to increase survival rates in animal models via enhanced and more homogeneous oxygenation. However, our knowledge of the biophysical mechanisms linking tumour decompression to improved tumour oxygenation is limited. In this study, we propose a computational model to investigate the impact of vessel compression on red blood cell (RBC) dynamics in tumour vascular networks. Our results demonstrate that vessel compression can alter RBC partitioning at bifurcations in a haematocrit-dependent and flowrate-independent manner. We identify RBC focussing due to cross-streamline migration as the mechanism responsible and characterise the spatiotemporal recovery dynamics controlling downstream partitioning. Based on this knowledge, we formulate a reduced-order model that will help future research to elucidate how these effects propagate at a whole vascular network level. These findings contribute to the mechanistic understanding of haemodilution in tumour vascular networks and oxygen homogenisation following pharmacological solid tumour decompression.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Kelly M. Knee ◽  
Amey Barakat ◽  
Lindsay Tomlinson ◽  
Lila Ramaiah ◽  
Zane Wenzel ◽  
...  

Sickle cell disease (SCD) is a severe genetic disorder caused by a mutation in hemoglobin (b6Glu-Val), which allows the mutant hemoglobin to assemble into long polymers when deoxygenated. Over time, these polymers build up and deform red blood cells, leading to hemolytic anemia, vaso-occlusion, and end organ damage. A number of recent therapies for SCD have focused on modulating the mutant hemoglobin directly, however, reduction or elimination of 2,3-DPG to reduce Hb S polymerization and RBC sickling has recently been proposed as a therapeutic strategy for SCD. Current clinical studies focus on activation of pyruvate kinase to reduce 2,3-DPG, however, direct targeting of the enzyme which produces 2,3-DPG; Bisphosphoglycerate Mutase (BPGM) may also be possible. In this study we evaluate the impact of elimination of 2,3-DPG on SCD pathology by complete knockout of BPGM in Townes model mice. Animals with complete knockout of BPGM (BPGM -/-) have no detectable 2,3-DPG, while animals that are heterozygous for BPGM (BPGM -/+) have 2,3-DPG levels comparable to Townes mice. Western Blot analysis confirms that BPGM -/- animals completely lack BPGM, while BPGM -/+ animals have BPGM levels that are nearly equivalent to Townes mice. As expected from the lack of 2,3-DPG, BPGM -/- animals have increased oxygen affinity, observed as a 39% decrease in p50 relative to Townes mice. Complete elimination of 2,3-DPG has significant effects on markers of hemolytic anemia in BPGM -/- mice. Mice lacking 2,3-DPG have a 60% increase in hemoglobin (3.7 g/dL), a 53% increase in red blood cell count, and a 29% increase in hematocrit relative to Townes mice. The BPGM -/- mice also have a 57% decrease in reticulocytes, and a 61% decrease in spleen weight relative to Townes animals, consistent with decreased extramedullary hematopoiesis. Consistent with the reduction in hemolysis, BPGM -/- animals had a 59% reduction in red blood cell sickling under robust hypoxic conditions. BPGM -/+ animals had hemoglobin, RBC, and hematocrit levels that were similar to Townes animals, and a similar degree of RBC sickling to Townes mice. Liver phenotype was similar across all variants, with areas of random necrosis observed in BPGM -/-, BPGM -/+ and Townes mice. Higher percentages of microcytic and/or hyperchromic RBCs were observed in BPGM -/- animals relative to BPGM -/+ or Townes animals. These results suggest that modulation of 2,3-DPG has a positive effect on RBC sickling and hemolytic anemia, which may have therapeutic benefits for SCD patients. However, the lack of improvement in organ damage suggests that modulation of 2,3-DPG alone may not be sufficient for complete elimination of SCD phenotypes, and further investigation of this therapeutic avenue may be necessary. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 162 (43) ◽  
pp. 1717-1723
Author(s):  
Sándor Pál ◽  
Barbara Réger ◽  
Tamás Kiss ◽  
Hussain Alizadeh ◽  
András Vereczkei ◽  
...  

Összefoglaló. Bevezetés: A COVID–19-világjárvány betegellátásra gyakorolt hatása hazánkban is jelentős. A vérellátást nehezítette a járványügyi intézkedések következményeként a véradási események elmaradása, a csökkent véradási hajlandóság, továbbá a nehezen megítélhető vérkészítményigény . A „Patient Blood Management” irányelveinek az orvosi gyakorlatban történő egyre szélesebb körű alkalmazása elősegíti az optimális vérkészítmény-felhasználást a transzfúziók lehetőség szerinti elkerülésével. Célkitűzés és módszer: Vizsgálatunk célja a Pécsi Tudományegyetem Klinikai Központjának Janus Pannonius Klinikai Tömbjében a vérkészítmény-felhasználás változásainak felmérése volt a 2020. év első öt hónapjában. Eredmények: A járványügyi intézkedéseket követő időszakban szignifikánsan csökkent a hospitalizált betegeknek (34,08%), a transzfúziót igénylő betegeknek (39,69%) és a felhasznált vörösvérsejt-készítményeknek (46,41%) a száma, valamint az egy betegre jutó felhasznált vörösvérsejt-koncentrátum átlaga (2,61-ről 1,97-re) is. Közel 30%-os arányban csökkent a felhasznált friss fagyasztott plazma egységeinek és a thrombocytakoncentrátumoknak a száma is. Következtetés: A szigorú korlátozások életbe léptetését követően a nehézségek ellenére sikerült elegendő mennyiségű vérkészítményt biztosítani a betegeknek. Az Országos Vérellátó Szolgálat Pécsi Regionális Vérellátó Központja munkatársainak és a klinikusok erőfeszítéseinek köszönhetően a vérkészítményigény és -kínálat között új egyensúly alakult ki, mely megfelelő ellátást biztosított a feltétlenül szükséges transzfúziók kivitelezéséhez. Orv Hetil. 2021; 162(43): 1717–1723. Summary. Introduction: The impact of COVID–19 pandemic on patient care is pronounced also in Hungary. Blood supply was hindered by the reduction of public blood donation events, the reduced willingness to donate, and the difficult predictability of blood product demand as a result of the epidemiological regulations. The wider application of Patient Blood Management guidelines in the medical practice will promote optimal blood product utilization by avoiding transfusions where possible. Objective and method: The aim of our study was to assess the changes in the usage of blood products in the first five months of 2020 at the Clinical Center of the University of Pécs, Janus Pannonius Clinical Building. Results: In the period following the epidemiological measures, we found reduction in the number of hospitalized patients (34.08%), in the number of patients requiring transfusion (39.69%) and in the number of red blood cell products used (46.41%). The number of transfused red blood cell concentrates per patient was also significantly reduced (from 2.61 to 1.97) in this period. The number of transfused fresh frozen plasma units and platelet concentrates also decreased by approximately 30%. Conclusion: After the implementation of the strict restrictions, despite the difficulties, it was possible to provide patients with sufficient blood products. Due to the efforts of both the Regional Blood Transfusion Center of Pécs of the Hungarian National Blood Transfusion Service and of the clinicians, a new balance was established between the demand and the supply of blood products, which provided adequate care for the necessary transfusions. Orv Hetil. 2021; 162(43): 1717–1723.


HPB ◽  
2017 ◽  
Vol 19 (4) ◽  
pp. 321-330 ◽  
Author(s):  
Sean Bennett ◽  
Laura K. Baker ◽  
Guillaume Martel ◽  
Risa Shorr ◽  
Timothy M. Pawlik ◽  
...  

Entropy ◽  
2019 ◽  
Vol 21 (11) ◽  
pp. 1062 ◽  
Author(s):  
Yuhang Dong ◽  
W. David Pan ◽  
Dongsheng Wu

Malaria is a severe public health problem worldwide, with some developing countries being most affected. Reliable remote diagnosis of malaria infection will benefit from efficient compression of high-resolution microscopic images. This paper addresses a lossless compression of malaria-infected red blood cell images using deep learning. Specifically, we investigate a practical approach where images are first classified before being compressed using stacked autoencoders. We provide probabilistic analysis on the impact of misclassification rates on compression performance in terms of the information-theoretic measure of entropy. We then use malaria infection image datasets to evaluate the relations between misclassification rates and actually obtainable compressed bit rates using Golomb–Rice codes. Simulation results show that the joint pattern classification/compression method provides more efficient compression than several mainstream lossless compression techniques, such as JPEG2000, JPEG-LS, CALIC, and WebP, by exploiting common features extracted by deep learning on large datasets. This study provides new insight into the interplay between classification accuracy and compression bitrates. The proposed compression method can find useful telemedicine applications where efficient storage and rapid transfer of large image datasets is desirable.


2019 ◽  
Vol 37 (2) ◽  
pp. 163-170 ◽  
Author(s):  
Andrew-Paul Deeb ◽  
Christopher T. Aquina ◽  
John R.T. Monson ◽  
Neil Blumberg ◽  
Adan Z. Becerra ◽  
...  

Background/Aims: Transfusion rates in colon cancer surgery are traditionally very high. Allogeneic red blood cell (RBC) transfusions are reported to induce immunomodulation that contributes to infectious morbidity and adverse oncologic outcomes. In an effort to attenuate these effects, the study institution implemented a universal leukocyte reduction protocol. The purpose of this study was to examine the impact of leukocyte-reduced (LR) transfusions on postoperative infectious complications, recurrence-free survival, and overall survival (OS). Methods: In a retrospective study, patients with stage I–III adenocarcinoma of the colon from 2003 to 2010 who underwent elective resection were studied. The primary outcome measures were postoperative infectious complications and recurrence-free and OS in patients that received a transfusion. Bivariate and multivariable regression analyses were performed for each endpoint. Results: Of 294 patients, 66 (22%) received a LR RBC transfusion. After adjustment, transfusion of LR RBCs was found to be independently associated with increased infectious complications (OR 3.10, 95% CI 1.24–7.73), increased odds of cancer recurrence (hazard ratio [HR] 3.74, 95% CI 1.94–7.21), and reduced OS when ≥3 units were administered (HR 2.24, 95% CI 1.12–4.48). Conclusion: Transfusion of LR RBCs is associated with an increased risk of infectious complications and worsened survival after elective surgery for colon cancer, irrespective of leukocyte reduction.


Surgery ◽  
2016 ◽  
Vol 159 (6) ◽  
pp. 1591-1599 ◽  
Author(s):  
Julie Hallet ◽  
Iryna Kulyk ◽  
Eva S.W. Cheng ◽  
Jessica Truong ◽  
Sherif S. Hanna ◽  
...  

2013 ◽  
Vol 23 (9) ◽  
pp. 1612-1619 ◽  
Author(s):  
Lindsay L. Morgenstern Warner ◽  
Sean C. Dowdy ◽  
Janice R. Martin ◽  
Maureen A. Lemens ◽  
Michaela E. McGree ◽  
...  

ObjectivePerioperative packed red blood cell transfusion (PRBCT) has been implicated as a negative prognostic marker in surgical oncology. There is a paucity of evidence on the impact of PRBCT on outcomes in epithelial ovarian cancer (EOC). We assessed whether PRBCT is an independent risk factor of recurrence and death from EOC.MethodsPerioperative patient characteristics and process-of-care variables (defined by the National Surgical Quality Improvement Program) were retrospectively abstracted from 587 women who underwent primary EOC staging between January 2, 2003, and December 29, 2008. Associations with receipt of PRBCT were evaluated using univariate logistic regression models. The associations between receipt of PRBCT and disease-free survival and overall survival were evaluated using multivariable Cox proportional hazards models and using propensity score matching and stratification, respectively.ResultsThe rate of PRBCT was 77.0%. The mean ± SD units transfused was 4.1 ± 3.1 U. In the univariate analysis, receipt of PRBCT was significantly associated with older age, advanced stage (≥IIIA), undergoing splenectomy, higher surgical complexity, serous histologic diagnosis, greater estimated blood loss, longer operating time, the presence of residual disease, and lower preoperative albumin and hemoglobin. Perioperative packed red blood cell transfusion was not associated with an increased risk for recurrence or death, in an analysis adjusting for other risk factors in a multivariable model or in an analysis using propensity score matching or stratification to control for differences between the patients with and without PRBCT.ConclusionsPerioperative packed red blood cell transfusion does not seem to be directly associated with recurrence and death in EOC. However, lower preoperative hemoglobin was associated with a higher risk for recurrence. The need for PRBCT seems to be a stronger prognostic indicator than the receipt of PRBCT.


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