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15 pages, 1242 KiB  
Article
Metabolic Effects of Sodium Thiosulfate During Resuscitation from Trauma and Hemorrhage in Cigarette-Smoke-Exposed Cystathionine-γ-Lyase Knockout Mice
by Maximilian Feth, Felix Hezel, Michael Gröger, Melanie Hogg, Fabian Zink, Sandra Kress, Andrea Hoffmann, Enrico Calzia, Ulrich Wachter, Peter Radermacher and Tamara Merz
Biomedicines 2024, 12(11), 2581; https://doi.org/10.3390/biomedicines12112581 - 12 Nov 2024
Viewed by 389
Abstract
Background: Acute and chronic pre-traumatic cigarette smoke exposure increases morbidity and mortality after trauma and hemorrhage. In mice with a genetic deletion of the H2S-producing enzyme cystathione-γ-lyase (CSE−/−), providing exogenous H2S using sodium thiosulfate (Na2S [...] Read more.
Background: Acute and chronic pre-traumatic cigarette smoke exposure increases morbidity and mortality after trauma and hemorrhage. In mice with a genetic deletion of the H2S-producing enzyme cystathione-γ-lyase (CSE−/−), providing exogenous H2S using sodium thiosulfate (Na2S2O3) improved organ function after chest trauma and hemorrhagic shock. Therefore, we evaluated the effect of Na2S2O3 during resuscitation from blunt chest trauma and hemorrhagic shock on CSE−/− mice with pre-traumatic cigarette smoke (CS) exposure. Since H2S is well established as being able to modify energy metabolism, a specific focus was placed on whole-body metabolic pathways and mitochondrial respiratory activity. Methods: Following CS exposure, the CSE−/− mice underwent anesthesia, surgical instrumentation, blunt chest trauma, hemorrhagic shock for over 1 h (target mean arterial pressure (MAP) ≈ 35 ± 5 mmHg), and resuscitation for up to 8 h comprising lung-protective mechanical ventilation, the re-transfusion of shed blood, fluid resuscitation, and continuous i.v. noradrenaline (NoA) to maintain an MAP ≥ 55 mmHg. At the start of the resuscitation, the mice randomly received either i.v. Na2S2O3 (0.45 mg/gbodyweight; n = 14) or the vehicle (NaCl 0.9%; n = 11). In addition to the hemodynamics, lung mechanics, gas exchange, acid–base status, and organ function, we quantified the parameters of carbohydrate, lipid, and protein metabolism using a primed continuous infusion of stable, non-radioactive, isotope-labeled substrates (gas chromatography/mass spectrometry) and the post-mortem tissue mitochondrial respiratory activity (“high-resolution respirometry”). Results: While the hemodynamics and NoA infusion rates did not differ, Na2S2O3 was associated with a trend towards lower static lung compliance (p = 0.071) and arterial PO2 (p = 0.089) at the end of the experiment. The direct, aerobic glucose oxidation rate was higher (p = 0.041) in the Na2S2O3-treated mice, which resulted in lower glycemia levels (p = 0.050) and a higher whole-body CO2 production rate (p = 0.065). The mitochondrial respiration in the heart, kidney, and liver tissue did not differ. While the kidney function was comparable, the Na2S2O3-treated mice showed a trend towards a shorter survival time (p = 0.068). Conclusions: During resuscitation from blunt chest trauma and hemorrhagic shock in CSE−/− mice with pre-traumatic CS exposure, Na2S2O3 was associated with increased direct, aerobic glucose oxidation, suggesting a switch in energy metabolism towards preferential carbohydrate utilization. Nevertheless, treatment with Na2S2O3 coincided with a trend towards worsened lung mechanics and gas exchange, and, ultimately, shorter survival. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutics in Hemorrhagic Shock)
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<p>Experimental setup, timeline, surgical instrumentation, and experimental protocol. MAP, mean arterial pressure; Na<sub>2</sub>S<sub>2</sub>O<sub>3</sub>, sodium thiosulfate; TxT, chest trauma; i.v., intravenous.</p>
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<p>Kaplan–Meier survival curve in the vehicle group (solid line) and Na<sub>2</sub>S<sub>2</sub>O<sub>3</sub> group (dotted line). Time “0” refers to the start of the observation period, with the initiation of blunt chest trauma. No significant differences were observed (log rank Mantel–Cox test, <span class="html-italic">p</span> = 0.068).</p>
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<p>The evaluation of metabolic pathways. The individual results as well as the median and interquartile range (endogenous glucose production rate) or mean ± standard deviation (glucose oxidation; glycerol, urea, and leucine production rates) are shown, according to the absence/presence of a normal data distribution for the metabolic parameters as assessed using stable, non-radioactive isotope-labeled substrates (glucose, glycerol, leucine, and urea) between mice in the vehicle (open circles) and the Na<sub>2</sub>S<sub>2</sub>O<sub>3</sub> (solid triangles) groups. Differences between the two treatment groups were analyzed using the Mann–Whitney U rank sum test or a Student’s <span class="html-italic">t</span>-test as appropriate.</p>
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<p>The evaluation of mitochondrial activity. The individual results as well as the median and interquartile range (liver OxPhos and ETC, kidney ETC) or mean ± standard deviation (heart OxPhos and ETC, kidney OxPhos) are shown according to the absence/presence of a normal data distribution for the parameters of mitochondrial respiratory activity in immediate postmortem specimens of the heart, liver, and kidney. The oxidative phosphorylation (OxPhos) (left panel) and maximal electron transfer capacity in the uncoupled state (ETC, right panel) are presented for mice in the vehicle (open circles) and Na<sub>2</sub>S<sub>2</sub>O<sub>3</sub> (solid triangles) groups. Differences between the two treatment groups were analyzed using the Mann–Whitney U rank sum test or a Student’s t-test as appropriate.</p>
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11 pages, 469 KiB  
Article
The Role of Robotic Cystectomy in the Salvage and Palliative Setting: A Retrospective, Single-Center, Cohort Study
by Aldo Brassetti, Loris Cacciatore, Flavia Proietti, Rigoberto Pallares-Méndez, Alfredo Maria Bove, Umberto Anceschi, Riccardo Mastroianni, Leonardo Misuraca, Gabriele Tuderti, Giuseppe Chiacchio, Mariaconsiglia Ferriero, Rocco Simone Flammia, Costantino Leonardo and Giuseppe Simone
Cancers 2024, 16(22), 3784; https://doi.org/10.3390/cancers16223784 - 10 Nov 2024
Viewed by 362
Abstract
Introduction: This article compares surgical and survival outcomes of robot-assisted and open radical cystectomy with cutaneous ureterostomy for the treatment of frail bladder cancer patients with limited life expectancy. Methods: The institutional database was searched for cystectomy cases with cutaneous ureterostomy, from 1 [...] Read more.
Introduction: This article compares surgical and survival outcomes of robot-assisted and open radical cystectomy with cutaneous ureterostomy for the treatment of frail bladder cancer patients with limited life expectancy. Methods: The institutional database was searched for cystectomy cases with cutaneous ureterostomy, from 1 June 2016 to 31 August 2022. The study population was split into two groups, according to the surgical approach. The baseline characteristics and surgical outcomes were compared. Logistic regression analyses identified predictors of major bleeding events (hemoglobin loss ≥ 3.5 g/dL or blood transfusion) and re-operation within 30 days from surgery. The Kaplan–Meier method estimated the impact of the robotic approach on overall survival and Cox regression analysis assessed its predictors. Results: A total of 145 patients were included: 30% (n = 43) underwent robotic cystectomy. Patients’ characteristics and tumor stages distribution were comparable in the two groups but those receiving a minimally invasive treatment showed significantly reduced times to flatus, bowel and hospital discharge (all p < 0.001). Although operation times were longer in this cohort, major bleeding events (60% vs. 89%) and postoperative severe complications (0 vs. 8%) (both p < 0.001) were less frequent compared to the open approach. A logistic regression showed that robotic surgery independently predicted major bleeding events (OR: 0.26; 95%CI 0.09–0.72; p = 0.02) but not the need for re-intervention. A Kaplan–Meier analysis showed that robotic cystectomy was associated with a significant advantage in terms of overall survival (LogRank = 0.03), and this result was confirmed by Cox regression analysis (HR: 0.39; 95%CI 0.14–0.94; p = 0.04). Conclusions: Robotic cystectomy with cutaneous ureterostomy may represent a viable option to treat frail bladder cancer patients, as the minimally invasive approach reduces the risk of bleeding and serious complications and provides a prompt restoration of bowel function and a shorter hospital stay compared to open surgery. Full article
(This article belongs to the Special Issue Advancements in Bladder Cancer Therapy)
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<p>Impact of robotics approach on overall survival probabilities.</p>
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13 pages, 1622 KiB  
Case Report
A Severe Case of Plasmodium falciparum Malaria in a 44-Year-Old Caucasian Woman on Return to Western Romania from a Visit to Nigeria
by Alin Gabriel Mihu, Rodica Lighezan, Daniela Adriana Oatis, Ovidiu Alexandru Mederle, Cristina Petrine-Mocanu, Cristina Petrescu, Mirandolina Eugenia Prisca, Laura Andreea Ghenciu, Cecilia Roberta Avram, Maria Alina Lupu, Adelaida Bica and Tudor Rareș Olariu
Life 2024, 14(11), 1454; https://doi.org/10.3390/life14111454 - 9 Nov 2024
Viewed by 503
Abstract
Malaria is currently the most prevalent life-threatening infectious disease in the world. In this case report, we present a 44-year-old Caucasian woman with a low level of education and no significant past medical history who presented to the emergency room of the Emergency [...] Read more.
Malaria is currently the most prevalent life-threatening infectious disease in the world. In this case report, we present a 44-year-old Caucasian woman with a low level of education and no significant past medical history who presented to the emergency room of the Emergency County Hospital of Arad, Romania, with a general affected state, a fever of 38.5 °C, chills, weakness, headache, muscle pain, nausea, icterus, and watery diarrheal stool. A viral infection was initially suspected, and the patient was transferred to the Infectious Diseases Department. The anamnesis revealed that the patient traveled to Nigeria (Ado Ekiti) and returned to Romania 14 days before presenting to the hospital without following antimalarial prophylaxis. A peripheral blood smear was conducted and revealed parasitemia with ring forms of Plasmodium falciparum (P. falciparum) of 10–15% within the red blood cells. Parasitemia increased within a day to 15–18%, and her health rapidly deteriorated. She was transferred to the Victor Babeș Infectious Disease Hospital in Bucharest for the urgent initiation of antimalarial treatment. The patient’s condition continued to worsen rapidly, and she succumbed to her illness due to multi-organ failure. This report details the first documented case of malaria imported from Nigeria to Romania. People traveling to malaria-endemic areas should be educated about preventing this parasitic infection, both by adopting measures to reduce the risk of mosquito bites and by using appropriate chemoprophylaxis. In the context of resuming travel after the COVID-19 pandemic, understanding and adhering to prophylactic measures is crucial to avoid tragic situations, as highlighted in this case report. Full article
(This article belongs to the Special Issue Trends in Microbiology 2024)
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<p>(<b>A</b>,<b>B</b>) May–Grunwald Giemsa-stained thin peripheral blood smear showing severe parasitemia with several ring forms of <span class="html-italic">Plasmodium falciparum </span>(×1000).</p>
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<p>May–Grunwald Giemsa-stained thin peripheral blood smear showing severe parasitemia with ring forms of <span class="html-italic">Plasmodium falciparum</span>. (<b>A</b>) A band neutrophil with toxic vacuoles. (<b>B</b>) Two metamyelocytes with toxic granules and vacuoles. (<b>C</b>) Two band neutrophils with toxic granules and vacuoles. (<b>D</b>) A giant metamyelocyte with several vacuoles, toxic granules, and an unsegmented neutrophil with toxic granules (×1000).</p>
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<p>May–Grunwald Giemsa-stained thin peripheral blood smear showing severe parasitemia with ring forms of <span class="html-italic">Plasmodium falciparum</span> with an (<b>A</b>) unsegmented neutrophil and (<b>B</b>) metamyelocyte, both with the malaria pigment (hemozoin) (×1000).</p>
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18 pages, 1528 KiB  
Article
Roxadustat Efficacy and Safety in Patients Receiving Peritoneal Dialysis: Pooled Analysis of Four Phase 3 Studies
by Danilo Fliser, Sunil Bhandari, Alberto Ortiz, Vicki Santos, Najib Khalife, Alina Jiletcovici and Tadao Akizawa
J. Clin. Med. 2024, 13(22), 6729; https://doi.org/10.3390/jcm13226729 - 8 Nov 2024
Viewed by 394
Abstract
Background/Objectives: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved to treat anemia of chronic kidney disease (CKD). The efficacy and safety of roxadustat compared with parenteral erythropoiesis-stimulating agents (ESAs) were evaluated in patients with anemia of CKD receiving peritoneal dialysis (PD). [...] Read more.
Background/Objectives: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved to treat anemia of chronic kidney disease (CKD). The efficacy and safety of roxadustat compared with parenteral erythropoiesis-stimulating agents (ESAs) were evaluated in patients with anemia of CKD receiving peritoneal dialysis (PD). Methods: This analysis pooled data from four phase 3, multicenter, randomized, open-label, active-comparator studies (PYRENEES, SIERRAS, HIMALAYAS, ROCKIES). The primary endpoints evaluated were hemoglobin change from baseline (CFB) to Weeks 28–36 without rescue therapy and hemoglobin CFB to Weeks 28–52 regardless of rescue therapy use. Safety data were reported. Results: This analysis included 422 patients (215 roxadustat, 207 ESA). Hemoglobin CFB to Weeks 28–36 without rescue therapy and hemoglobin CFB to Weeks 28–52 regardless of rescue therapy achieved non-inferiority for roxadustat vs. ESAs. The mean weekly dose of roxadustat was maintained over time (Weeks 1–4, 3.86 mg/kg/week; Weeks 101–104, 3.27 mg/kg/week), whereas the mean weekly ESA dose increased by 24% (Weeks 1–4, 115.70 IU/kg/week; Weeks 101–104, 143.40 IU/kg/week). Fewer patients treated with roxadustat received intravenous iron supplementation and rescue therapy, and patients treated with an ESA required blood transfusions sooner. Roxadustat-treated patients experienced a greater decrease in low-density lipoprotein cholesterol levels relative to baseline vs. ESA-treated patients. Treatment-emergent adverse events were similar in both treatment groups. Major adverse cardiovascular event (MACE), MACE plus unstable angina or congestive heart failure, and all-cause mortality hazard ratios were <1; the lower limit of the 95% CIs was <0.6, and the upper limit was >1.3. Conclusions: Roxadustat was non-inferior to ESAs in correcting and maintaining hemoglobin levels, with stable dosing and a comparable safety profile, in anemic patients receiving PD. Full article
(This article belongs to the Special Issue New Insights into Peritoneal Dialysis and Hemodialysis)
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<p>Studies included in the pooled analysis. DA, darbepoetin alfa; EPO-α, epoetin alfa.</p>
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<p>Mean Hb levels (g/dL, lines) and mean weekly total dose (columns) of roxadustat (<b>A</b>) or ESA (<b>B</b>) from baseline to Week 104. ESA, erythropoiesis-stimulating agent; Hb, hemoglobin; SE, standard error.</p>
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<p>Time to rescue therapy with RBC transfusion for patients treated with roxadustat or ESA from baseline to Week 52. <span class="html-italic">p</span> value determined by log-rank test. ESA, erythropoiesis-stimulating agent; RBC, red blood cell.</p>
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22 pages, 3131 KiB  
Review
Fetal Red Blood Cells: A Comprehensive Review of Biological Properties and Implications for Neonatal Transfusion
by Claudio Pellegrino, Elizabeth F. Stone, Caterina Giovanna Valentini and Luciana Teofili
Cells 2024, 13(22), 1843; https://doi.org/10.3390/cells13221843 - 7 Nov 2024
Viewed by 859
Abstract
Transfusion guidelines worldwide include recommendations regarding the storage length, irradiation, or even donor cytomegalovirus serostatus of red blood cell (RBC) units for anemic neonates. Nevertheless, it is totally overlooked that RBCs of these patients fundamentally differ from those of older children and adults. [...] Read more.
Transfusion guidelines worldwide include recommendations regarding the storage length, irradiation, or even donor cytomegalovirus serostatus of red blood cell (RBC) units for anemic neonates. Nevertheless, it is totally overlooked that RBCs of these patients fundamentally differ from those of older children and adults. These differences vary from size, shape, hemoglobin composition, and oxygen transport to membrane characteristics, cellular metabolism, and lifespan. Due to these profound dissimilarities, repeated transfusions of adult RBCs in neonates deeply modify the physiology of circulating RBC populations. Unsurprisingly, the number of RBC transfusions in preterm neonates, particularly if born before 28 weeks of gestation, predicts morbidity and mortality. This review provides a comprehensive description of the biological properties of fetal, cord blood, and neonatal RBCs, including the implications that neonatal RBCs, and their replacement by adult RBCs, may have for perinatal disease pathophysiology. Full article
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<p>Overview of the main molecular networks and metabolic pathways relevant to fetal and neonatal RBC physiology. Blue arrows pointing upward denote increased concentration or activity in relation to adult RBCs. Blue arrows pointing downward indicate decreased concentration or activity. Abbreviations: AQP1 aquaporin 1, ARA arachidonic acid, ATP adenosine triphosphate, BCL11A B-cell lymphoma/leukemia 11A, CA I/II carbonic anhydrase I/II, CAT catalase, Cl− chloride ion, CL cholesterol, CO<sub>2</sub> carbon dioxide, DHA docosahexaenoic acid, DNMT3B DNA methyltransferase 3B, ENL enolase, eNOS endothelial nitric oxide synthase, FASD2 fatty acid desaturase 2, fRBC fetal RBCs, GAPDH glyceraldehyde-3-phosphate dehydrogenase, GLN glutamine, GLUT glucose transporter, GSSG glutathione disulphide, GSH glutathione, GPX glutathione peroxidase, GST glutathione S-transferase, GRXs glutaredoxins, Hb hemoglobin, HbA adult hemoglobin, HbF fetal hemoglobin, HCO3 bicarbonate, H<sub>2</sub>O water, H<sub>2</sub>O<sub>2</sub> hydrogen peroxide, LPC lysophosphatidylcholines, Lu/BCAM Lutheran blood group and basal cell adhesion molecule, K+ potassium ion, KDM1A lysis Met methionine, MYH9 myosin heavy chain 9, MYH10 myosin heavy chain 9, MYL12A myosin regulatory light chain 12A, Na+ sodium ion, NO nitric oxide, O<sub>2</sub> molecular oxygen, •O<sub>2</sub> superoxide, PC phosphatidylcholine, PE phosphatidylethanolamine, PFK phosphofructokinase-1, PGK phosphoglycerate kinase, PI phosphatidylinositol, PS phosphatidylserine, Prx2 Peroxiredoxin 2, ROS reactive oxygen species, Sema-7A Semaphorin 7A, SM sphingomyelin, SOD superoxide dismutase, TXR1 thioredoxin 1, 2,3-DPG 2,3-diphosphoglycerate. Created in <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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<p>Schematic demonstrating how RBCs age and die in preterm neonates. RBCs from hematopoiesis or transfusion circulate through the microvasculature in preterm neonates. Considerable RBC damage accumulates over time from ROS, mechanical injury, and osmotic stress, and this leads to RBC senescence. RBCs are then cleared by extravascular or intravascular hemolysis and by eryptosis. ROS: reactive oxygen species. Created in <a href="http://BioRender.com" target="_blank">BioRender.com</a>.</p>
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18 pages, 4490 KiB  
Article
Is Serum Ferritin a Predictor of Blood Transfusions Outcome and Survival in Childhood Lymphomas and Solid Tumors?
by Małgorzata Sawicka-Żukowska, Anna Krętowska-Grunwald, Magdalena Topczewska, Maryna Krawczuk-Rybak and Kamil Grubczak
Cancers 2024, 16(22), 3742; https://doi.org/10.3390/cancers16223742 - 6 Nov 2024
Viewed by 436
Abstract
Packed red blood cell (PRBC) transfusions are an important part of supportive treatment in oncology; however, when used frequently, they can be a result of transfusion-related iron overload. The aim of the study was to evaluate the role of ferritin as a non-specific [...] Read more.
Packed red blood cell (PRBC) transfusions are an important part of supportive treatment in oncology; however, when used frequently, they can be a result of transfusion-related iron overload. The aim of the study was to evaluate the role of ferritin as a non-specific marker of neoplastic growth and transfusion-related iron overload in children with lymphomas and solid tumors. We performed a longitudinal analysis of PRBC transfusions and changes in ferritin concentrations during oncological treatment of 88 children with lymphomas and solid tumors. A ferritin concentration above 500 ng/mL was diagnosed in 14.77% of patients at the moment of admission and 18.18% at the end of treatment. No differences were shown in serum ferritin in the context of tumor type-, sex-, and transfusion-related parameters. Those above the age of 10 demonstrated higher ferritin concentrations compared to subjects younger than 5 years of age. In addition, those over than 10 years old or above 30 kg in weight showed a tendency for better survival. All tested patients demonstrated highly significant correlations between ferritin at the 15th month of treatment or after therapy discontinuation and transfusion-related parameters. Interestingly, ferritin levels were found to lower back to the values before therapy shortly after its discontinuation. Transfusion parameters and ferritin levels had no influence on the survival of the studied cancer patients. Full article
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Graphical abstract
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<p>Pre-treatment blood ferritin levels in studied lymphoma and solid tumor patients. Initial ferritin concentrations between the total group of lymphoma and solid tumor subjects (<b>A</b>), additionally including stratification based on sex (<b>B</b>), age (<b>C</b>), or weight (<b>D</b>). Transfusion-related parameters’ influence on ferritin concentration: total volume of blood used (<b>E</b>), volume of transfused blood per kilogram (<b>F</b>), units of blood transferred (<b>G</b>). Data are presented as median values and 25th–75th percentile.</p>
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<p>Therapy-induced variations in ferritin level in studied cancer patients. Changes in serum ferritin levels in total lymphoma and solid tumor groups (<b>A</b>), additionally including stratification based on sex (<b>B</b>), age (<b>C</b>), and weight (<b>D</b>). Transfusion-related parameters’ influence on ferritin concentration: total volume of blood used (<b>E</b>), volume of transfused blood per kilogram (<b>F</b>), units of blood transferred (<b>G</b>), and pre-treatment ferritin levels (<b>H</b>). Data are presented as median values and 25th–75th percentile, showing the percentage of ferritin change over time from the first time point (0 months). Statistical significance indicated with asterisks or <span class="html-italic">p</span> value. *—<span class="html-italic">p</span> &lt; 0.05, **—<span class="html-italic">p</span> &lt; 0.01, ***—<span class="html-italic">p</span> &lt; 0.001, ****—<span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>Correlations between ferritin levels in therapy and transfusion-related data in studied patients. Evaluated time points included: 0 (T0) and 15 (T5) months, the after-therapy point (T6), and the change between those periods. Correlations were assessed within the total group of patients (<b>A</b>) and in lymphoma (<b>B</b>) and solid tumor (<b>C</b>) patients individually. Data are presented on heat-maps as correlation coefficient (<span class="html-italic">r</span>) values, and statistical significance is indicated with asterisks or <span class="html-italic">p</span> value. *—<span class="html-italic">p</span> &lt; 0.05, **—<span class="html-italic">p</span> &lt; 0.01, ***—<span class="html-italic">p</span> &lt; 0.001, ****—<span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>Distribution of relapse and death incidents in lymphoma and solid tumor patients. Chi-square analysis was performed individually, including tumor type (<b>A</b>), age (<b>B</b>), sex (<b>C</b>), and weight (<b>D</b>). Data show the frequency of death/relapse incidence in specific subgroups. Data significance is indicated with exact <span class="html-italic">p</span> values.</p>
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<p>Distribution of relapse and death incidents in lymphoma and solid tumor patients. Chi-square analysis was performed individually, focusing on transfusion-related parameters: total blood volume transfused (<b>A</b>), blood volume used per kilogram (<b>B</b>), total blood units transfused (<b>C</b>), pre-treatment ferritin levels (<b>D</b>), and direction of ferritin change in therapy (After versus T0 time point) (<b>E</b>). Data show the frequency of death/relapse incidence in specific subgroups, and exact <span class="html-italic">p</span> values are provided.</p>
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<p>Significance of basic clinical data in reference to studied patients’ survival. Survival curves of the patients analyzed in the context of tumor type (<b>A</b>), sex (<b>B</b>), age (<b>C</b>), and weight (<b>D</b>). Data are presented as survival percentages during therapy, with log-rank test results and median overall survival indicated (mOS).</p>
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<p>Significance of ferritin- and transfusion-related parameters’ influence on survival of the studied patients. Survival curves of the patients analyzed in the context of total blood volume transfused (<b>A</b>), blood volume used per kilogram (<b>B</b>), total blood units transfused (<b>C</b>), pre-treatment ferritin levels (<b>D</b>), and direction of ferritin change in therapy (After versus T0 time point) (<b>E</b>,<b>F</b>). Data are presented as survival percentages in therapy, with log-rank test results and overall survival indicated (OS).</p>
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32 pages, 1452 KiB  
Systematic Review
Midwife-Led Versus Obstetrician-Led Perinatal Care for Low-Risk Pregnancy: A Systematic Review and Meta-Analysis of 1.4 Million Pregnancies
by Shyamkumar Sriram, Fahad M. Almutairi and Muayad Albadrani
J. Clin. Med. 2024, 13(22), 6629; https://doi.org/10.3390/jcm13226629 - 5 Nov 2024
Viewed by 608
Abstract
Background: The optimum model of perinatal care for low-risk pregnancies has been a topic of debate. Obstetrician-led care tends to perform unnecessary interventions, whereas the quality of midwife-led care has been subject to debate. This review aimed to assess whether midwife-led care reduces [...] Read more.
Background: The optimum model of perinatal care for low-risk pregnancies has been a topic of debate. Obstetrician-led care tends to perform unnecessary interventions, whereas the quality of midwife-led care has been subject to debate. This review aimed to assess whether midwife-led care reduces childbirth intervention and whether this comes at the expense of maternal and neonatal wellbeing. Methods: PubMed, Scopus, Cochrane Library, and Web of Science were systematically searched for relevant studies. Studies were checked for eligibility by screening the titles, abstracts, and full texts. We performed meta-analyses using the inverse variance method using RevMan software version 5.3. We pooled data using the risk ratio and mean difference with the 95% confidence interval. Results: This review included 44 studies with 1,397,320 women enrolled. Midwife-led care carried a lower risk of unplanned cesarean and instrumental vaginal deliveries, augmentation of labor, epidural/spinal analgesia, episiotomy, and active management of labor third stage. Women who received midwife-led care had shorter hospital stays and lower risks of infection, manual removal of the placenta, blood transfusion, and intensive care unit (ICU) admission. Furthermore, neonates delivered under midwife-led care had lower risks of acidosis, asphyxia, transfer to specialist care, and ICU admission. Postpartum hemorrhage, perineal tears, APGAR score < 7, and other outcomes were comparable between the two models of management. Conclusions: Midwife-led care reduced childbirth interventions with favorable maternal and neonatal outcomes in most cases. We recommend assigning low-risk pregnancies to midwife-led perinatal care in health systems with infrastructure allowing for smooth transfer when complications arise. Further research is needed to reflect the situation in low-resource countries. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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<p>PRISMA flow diagram.</p>
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<p>Forest plot of the analysis; unplanned cesarean section [<a href="#B22-jcm-13-06629" class="html-bibr">22</a>,<a href="#B23-jcm-13-06629" class="html-bibr">23</a>,<a href="#B24-jcm-13-06629" class="html-bibr">24</a>,<a href="#B27-jcm-13-06629" class="html-bibr">27</a>,<a href="#B28-jcm-13-06629" class="html-bibr">28</a>,<a href="#B29-jcm-13-06629" class="html-bibr">29</a>,<a href="#B30-jcm-13-06629" class="html-bibr">30</a>,<a href="#B35-jcm-13-06629" class="html-bibr">35</a>,<a href="#B36-jcm-13-06629" class="html-bibr">36</a>,<a href="#B37-jcm-13-06629" class="html-bibr">37</a>,<a href="#B39-jcm-13-06629" class="html-bibr">39</a>,<a href="#B43-jcm-13-06629" class="html-bibr">43</a>,<a href="#B44-jcm-13-06629" class="html-bibr">44</a>,<a href="#B45-jcm-13-06629" class="html-bibr">45</a>,<a href="#B47-jcm-13-06629" class="html-bibr">47</a>,<a href="#B48-jcm-13-06629" class="html-bibr">48</a>,<a href="#B49-jcm-13-06629" class="html-bibr">49</a>,<a href="#B50-jcm-13-06629" class="html-bibr">50</a>,<a href="#B51-jcm-13-06629" class="html-bibr">51</a>,<a href="#B52-jcm-13-06629" class="html-bibr">52</a>,<a href="#B53-jcm-13-06629" class="html-bibr">53</a>,<a href="#B54-jcm-13-06629" class="html-bibr">54</a>,<a href="#B55-jcm-13-06629" class="html-bibr">55</a>,<a href="#B56-jcm-13-06629" class="html-bibr">56</a>,<a href="#B57-jcm-13-06629" class="html-bibr">57</a>,<a href="#B59-jcm-13-06629" class="html-bibr">59</a>,<a href="#B60-jcm-13-06629" class="html-bibr">60</a>,<a href="#B61-jcm-13-06629" class="html-bibr">61</a>,<a href="#B62-jcm-13-06629" class="html-bibr">62</a>,<a href="#B63-jcm-13-06629" class="html-bibr">63</a>,<a href="#B65-jcm-13-06629" class="html-bibr">65</a>,<a href="#B66-jcm-13-06629" class="html-bibr">66</a>,<a href="#B67-jcm-13-06629" class="html-bibr">67</a>,<a href="#B68-jcm-13-06629" class="html-bibr">68</a>,<a href="#B69-jcm-13-06629" class="html-bibr">69</a>].</p>
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<p>Forest plot of the analysis; instrumental vaginal delivery [<a href="#B22-jcm-13-06629" class="html-bibr">22</a>,<a href="#B23-jcm-13-06629" class="html-bibr">23</a>,<a href="#B24-jcm-13-06629" class="html-bibr">24</a>,<a href="#B27-jcm-13-06629" class="html-bibr">27</a>,<a href="#B28-jcm-13-06629" class="html-bibr">28</a>,<a href="#B29-jcm-13-06629" class="html-bibr">29</a>,<a href="#B30-jcm-13-06629" class="html-bibr">30</a>,<a href="#B35-jcm-13-06629" class="html-bibr">35</a>,<a href="#B36-jcm-13-06629" class="html-bibr">36</a>,<a href="#B37-jcm-13-06629" class="html-bibr">37</a>,<a href="#B39-jcm-13-06629" class="html-bibr">39</a>,<a href="#B43-jcm-13-06629" class="html-bibr">43</a>,<a href="#B44-jcm-13-06629" class="html-bibr">44</a>,<a href="#B45-jcm-13-06629" class="html-bibr">45</a>,<a href="#B47-jcm-13-06629" class="html-bibr">47</a>,<a href="#B48-jcm-13-06629" class="html-bibr">48</a>,<a href="#B49-jcm-13-06629" class="html-bibr">49</a>,<a href="#B50-jcm-13-06629" class="html-bibr">50</a>,<a href="#B51-jcm-13-06629" class="html-bibr">51</a>,<a href="#B52-jcm-13-06629" class="html-bibr">52</a>,<a href="#B53-jcm-13-06629" class="html-bibr">53</a>,<a href="#B54-jcm-13-06629" class="html-bibr">54</a>,<a href="#B55-jcm-13-06629" class="html-bibr">55</a>,<a href="#B56-jcm-13-06629" class="html-bibr">56</a>,<a href="#B57-jcm-13-06629" class="html-bibr">57</a>,<a href="#B59-jcm-13-06629" class="html-bibr">59</a>,<a href="#B60-jcm-13-06629" class="html-bibr">60</a>,<a href="#B61-jcm-13-06629" class="html-bibr">61</a>,<a href="#B62-jcm-13-06629" class="html-bibr">62</a>,<a href="#B63-jcm-13-06629" class="html-bibr">63</a>,<a href="#B65-jcm-13-06629" class="html-bibr">65</a>,<a href="#B66-jcm-13-06629" class="html-bibr">66</a>,<a href="#B67-jcm-13-06629" class="html-bibr">67</a>,<a href="#B68-jcm-13-06629" class="html-bibr">68</a>,<a href="#B69-jcm-13-06629" class="html-bibr">69</a>].</p>
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<p>Forest plot of the analysis; epidural or spinal analgesia [<a href="#B22-jcm-13-06629" class="html-bibr">22</a>,<a href="#B23-jcm-13-06629" class="html-bibr">23</a>,<a href="#B24-jcm-13-06629" class="html-bibr">24</a>,<a href="#B27-jcm-13-06629" class="html-bibr">27</a>,<a href="#B28-jcm-13-06629" class="html-bibr">28</a>,<a href="#B29-jcm-13-06629" class="html-bibr">29</a>,<a href="#B30-jcm-13-06629" class="html-bibr">30</a>,<a href="#B35-jcm-13-06629" class="html-bibr">35</a>,<a href="#B36-jcm-13-06629" class="html-bibr">36</a>,<a href="#B37-jcm-13-06629" class="html-bibr">37</a>,<a href="#B39-jcm-13-06629" class="html-bibr">39</a>,<a href="#B43-jcm-13-06629" class="html-bibr">43</a>,<a href="#B44-jcm-13-06629" class="html-bibr">44</a>,<a href="#B45-jcm-13-06629" class="html-bibr">45</a>,<a href="#B47-jcm-13-06629" class="html-bibr">47</a>,<a href="#B48-jcm-13-06629" class="html-bibr">48</a>,<a href="#B49-jcm-13-06629" class="html-bibr">49</a>,<a href="#B50-jcm-13-06629" class="html-bibr">50</a>,<a href="#B51-jcm-13-06629" class="html-bibr">51</a>,<a href="#B52-jcm-13-06629" class="html-bibr">52</a>,<a href="#B53-jcm-13-06629" class="html-bibr">53</a>,<a href="#B54-jcm-13-06629" class="html-bibr">54</a>,<a href="#B55-jcm-13-06629" class="html-bibr">55</a>,<a href="#B56-jcm-13-06629" class="html-bibr">56</a>,<a href="#B57-jcm-13-06629" class="html-bibr">57</a>,<a href="#B59-jcm-13-06629" class="html-bibr">59</a>,<a href="#B60-jcm-13-06629" class="html-bibr">60</a>,<a href="#B61-jcm-13-06629" class="html-bibr">61</a>,<a href="#B62-jcm-13-06629" class="html-bibr">62</a>,<a href="#B63-jcm-13-06629" class="html-bibr">63</a>,<a href="#B65-jcm-13-06629" class="html-bibr">65</a>,<a href="#B66-jcm-13-06629" class="html-bibr">66</a>,<a href="#B67-jcm-13-06629" class="html-bibr">67</a>,<a href="#B68-jcm-13-06629" class="html-bibr">68</a>,<a href="#B69-jcm-13-06629" class="html-bibr">69</a>].</p>
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<p>Forest plot of the analysis; postpartum hemorrhage [<a href="#B22-jcm-13-06629" class="html-bibr">22</a>,<a href="#B23-jcm-13-06629" class="html-bibr">23</a>,<a href="#B24-jcm-13-06629" class="html-bibr">24</a>,<a href="#B27-jcm-13-06629" class="html-bibr">27</a>,<a href="#B28-jcm-13-06629" class="html-bibr">28</a>,<a href="#B29-jcm-13-06629" class="html-bibr">29</a>,<a href="#B30-jcm-13-06629" class="html-bibr">30</a>,<a href="#B35-jcm-13-06629" class="html-bibr">35</a>,<a href="#B36-jcm-13-06629" class="html-bibr">36</a>,<a href="#B37-jcm-13-06629" class="html-bibr">37</a>,<a href="#B39-jcm-13-06629" class="html-bibr">39</a>,<a href="#B43-jcm-13-06629" class="html-bibr">43</a>,<a href="#B44-jcm-13-06629" class="html-bibr">44</a>,<a href="#B45-jcm-13-06629" class="html-bibr">45</a>,<a href="#B47-jcm-13-06629" class="html-bibr">47</a>,<a href="#B48-jcm-13-06629" class="html-bibr">48</a>,<a href="#B49-jcm-13-06629" class="html-bibr">49</a>,<a href="#B50-jcm-13-06629" class="html-bibr">50</a>,<a href="#B51-jcm-13-06629" class="html-bibr">51</a>,<a href="#B52-jcm-13-06629" class="html-bibr">52</a>,<a href="#B53-jcm-13-06629" class="html-bibr">53</a>,<a href="#B54-jcm-13-06629" class="html-bibr">54</a>,<a href="#B55-jcm-13-06629" class="html-bibr">55</a>,<a href="#B56-jcm-13-06629" class="html-bibr">56</a>,<a href="#B57-jcm-13-06629" class="html-bibr">57</a>,<a href="#B59-jcm-13-06629" class="html-bibr">59</a>,<a href="#B60-jcm-13-06629" class="html-bibr">60</a>,<a href="#B61-jcm-13-06629" class="html-bibr">61</a>,<a href="#B62-jcm-13-06629" class="html-bibr">62</a>,<a href="#B63-jcm-13-06629" class="html-bibr">63</a>,<a href="#B65-jcm-13-06629" class="html-bibr">65</a>,<a href="#B66-jcm-13-06629" class="html-bibr">66</a>,<a href="#B67-jcm-13-06629" class="html-bibr">67</a>,<a href="#B68-jcm-13-06629" class="html-bibr">68</a>,<a href="#B69-jcm-13-06629" class="html-bibr">69</a>].</p>
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<p>Forest plot of the analysis; APGAR score &lt; 7 [<a href="#B22-jcm-13-06629" class="html-bibr">22</a>,<a href="#B23-jcm-13-06629" class="html-bibr">23</a>,<a href="#B24-jcm-13-06629" class="html-bibr">24</a>,<a href="#B27-jcm-13-06629" class="html-bibr">27</a>,<a href="#B28-jcm-13-06629" class="html-bibr">28</a>,<a href="#B29-jcm-13-06629" class="html-bibr">29</a>,<a href="#B30-jcm-13-06629" class="html-bibr">30</a>,<a href="#B35-jcm-13-06629" class="html-bibr">35</a>,<a href="#B36-jcm-13-06629" class="html-bibr">36</a>,<a href="#B37-jcm-13-06629" class="html-bibr">37</a>,<a href="#B39-jcm-13-06629" class="html-bibr">39</a>,<a href="#B43-jcm-13-06629" class="html-bibr">43</a>,<a href="#B44-jcm-13-06629" class="html-bibr">44</a>,<a href="#B45-jcm-13-06629" class="html-bibr">45</a>,<a href="#B47-jcm-13-06629" class="html-bibr">47</a>,<a href="#B48-jcm-13-06629" class="html-bibr">48</a>,<a href="#B49-jcm-13-06629" class="html-bibr">49</a>,<a href="#B50-jcm-13-06629" class="html-bibr">50</a>,<a href="#B51-jcm-13-06629" class="html-bibr">51</a>,<a href="#B52-jcm-13-06629" class="html-bibr">52</a>,<a href="#B53-jcm-13-06629" class="html-bibr">53</a>,<a href="#B54-jcm-13-06629" class="html-bibr">54</a>,<a href="#B55-jcm-13-06629" class="html-bibr">55</a>,<a href="#B56-jcm-13-06629" class="html-bibr">56</a>,<a href="#B57-jcm-13-06629" class="html-bibr">57</a>,<a href="#B59-jcm-13-06629" class="html-bibr">59</a>,<a href="#B60-jcm-13-06629" class="html-bibr">60</a>,<a href="#B61-jcm-13-06629" class="html-bibr">61</a>,<a href="#B62-jcm-13-06629" class="html-bibr">62</a>,<a href="#B63-jcm-13-06629" class="html-bibr">63</a>,<a href="#B65-jcm-13-06629" class="html-bibr">65</a>,<a href="#B66-jcm-13-06629" class="html-bibr">66</a>,<a href="#B67-jcm-13-06629" class="html-bibr">67</a>,<a href="#B68-jcm-13-06629" class="html-bibr">68</a>,<a href="#B69-jcm-13-06629" class="html-bibr">69</a>].</p>
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<p>Forest plot of the analysis; intrapartum or neonatal mortality [<a href="#B35-jcm-13-06629" class="html-bibr">35</a>,<a href="#B39-jcm-13-06629" class="html-bibr">39</a>,<a href="#B43-jcm-13-06629" class="html-bibr">43</a>,<a href="#B45-jcm-13-06629" class="html-bibr">45</a>,<a href="#B47-jcm-13-06629" class="html-bibr">47</a>,<a href="#B48-jcm-13-06629" class="html-bibr">48</a>,<a href="#B49-jcm-13-06629" class="html-bibr">49</a>,<a href="#B50-jcm-13-06629" class="html-bibr">50</a>,<a href="#B51-jcm-13-06629" class="html-bibr">51</a>,<a href="#B53-jcm-13-06629" class="html-bibr">53</a>,<a href="#B54-jcm-13-06629" class="html-bibr">54</a>,<a href="#B55-jcm-13-06629" class="html-bibr">55</a>,<a href="#B56-jcm-13-06629" class="html-bibr">56</a>,<a href="#B57-jcm-13-06629" class="html-bibr">57</a>,<a href="#B59-jcm-13-06629" class="html-bibr">59</a>,<a href="#B60-jcm-13-06629" class="html-bibr">60</a>,<a href="#B61-jcm-13-06629" class="html-bibr">61</a>,<a href="#B62-jcm-13-06629" class="html-bibr">62</a>,<a href="#B63-jcm-13-06629" class="html-bibr">63</a>,<a href="#B65-jcm-13-06629" class="html-bibr">65</a>,<a href="#B66-jcm-13-06629" class="html-bibr">66</a>,<a href="#B67-jcm-13-06629" class="html-bibr">67</a>,<a href="#B68-jcm-13-06629" class="html-bibr">68</a>,<a href="#B69-jcm-13-06629" class="html-bibr">69</a>].</p>
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12 pages, 1163 KiB  
Article
Cirrhosis Progression Is Not Associated with Clinically Significant Alterations in Global Hemostasis Assessed by Thromboelastography
by Rareș Crăciun, Alina Buliarcă, Daniela Matei, Cristiana Grapă, Iuliana Nenu, Horia Ștefănescu, Tudor Mocan, Bogdan Procopeț and Zeno Spârchez
J. Clin. Med. 2024, 13(21), 6614; https://doi.org/10.3390/jcm13216614 - 4 Nov 2024
Viewed by 459
Abstract
(1) Background: Cirrhosis is associated with frequent alterations in standard coagulation tests that do not adequately reflect hemostasis. Thromboelastography provides a global assessment of coagulation and evaluates the functional status of clotting factors, fibrinogen, platelets, and fibrinolysis. The study aimed to assess whether [...] Read more.
(1) Background: Cirrhosis is associated with frequent alterations in standard coagulation tests that do not adequately reflect hemostasis. Thromboelastography provides a global assessment of coagulation and evaluates the functional status of clotting factors, fibrinogen, platelets, and fibrinolysis. The study aimed to assess whether liver disease severity leads to progressive alterations in the thromboelastography-based assessment of coagulation. (2) Methods: Consecutive patients with cirrhosis and abnormal standard coagulation tests (at least one of International Normalized Ratio > 2, platelet count < 50 × 103/µL, fibrinogen < 200 mg/dL) were analyzed using native thromboelastography. (3) Results: A total of 106 patients were included, of whom 69 (65.1%) had a normal thromboelastography. While the standard coagulation tests were significantly worse in patients in the Child C group (n = 62, 58.5%) than in patients staged in Child A and B, no significant differences existed between any of the thromboelastography variables. Of the 50 patients (47.1%) with an International Normalized Ratio > 2, only two patients (4%) had features of hypocoagulation, while 26% had features of hypercoagulability on thromboelastography. Patients with a platelet count < 50 × 103/µL had significantly lower platelet function as assessed by thromboelastography, yet only eight patients (20%) met the criteria for platelet transfusion. A thromboelastography-based transfusion protocol might lead to a 94.6% reduction in blood product transfusion indications in a simulation where the included patients would require interventional procedures. (4) Conclusion: Standard coagulation tests showed a poor correlation with thromboelastography. Based on thromboelastography, patients with severe, decompensated liver disease have a preserved hemostasis balance despite abnormal standard coagulation tests. Therefore, standard coagulation tests should not be used to guide the administration of blood products in patients with cirrhosis. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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<p>A normal thromboelastography curve. The R-value signifies reaction time, indicating latency to initial fibrin formation. K (kinetics) measures the time to achieve a certain clot strength. The alpha angle assesses fibrin build-up speed in the initiation phase. MA (maximum amplitude) represents ultimate clot strength, dependent on platelets and fibrin. LY30 gauges fibrinolysis. Together, these variables encompass clotting and fibrinolysis processes, providing a comprehensive understanding of clot dynamics and stability in various phases of hemostasis.</p>
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10 pages, 657 KiB  
Article
Association Between Laboratory Coagulation Parameters and Postpartum Hemorrhage in Preterm and Term Caesarean Section: A Retrospective Analysis
by Christoph Dibiasi, Emilia Jecel, Veronica Falcone, Eva Schaden and Johannes Gratz
J. Clin. Med. 2024, 13(21), 6604; https://doi.org/10.3390/jcm13216604 - 3 Nov 2024
Viewed by 541
Abstract
Background: Deranged antepartum laboratory parameters may be risk factors for postpartum hemorrhage (PPH). However, whether this is also valid in women who give birth prematurely is currently unknown. Methods: We performed a retrospective single-center study to assess the role of antepartum hemoglobin, platelet [...] Read more.
Background: Deranged antepartum laboratory parameters may be risk factors for postpartum hemorrhage (PPH). However, whether this is also valid in women who give birth prematurely is currently unknown. Methods: We performed a retrospective single-center study to assess the role of antepartum hemoglobin, platelet count, fibrinogen, activated partial thromboplastin time, and prothrombin time as risk factors for PPH following caesarean section. We defined PPH as documented blood loss of at least 1 L and/or transfusion of red blood cell concentrates. We stratified the included patients according to gestational age: extremely preterm (gestational age < 28 weeks), very preterm (gestational age between 28 and 32 weeks), late and moderate preterm (gestational age between 32 and 37 weeks), and term (gestational age ≥ 37 weeks). Results: We included 1734 patients, 112 (6%) of whom had PPH. In total, 19 patients (10%) were in the extremely preterm group, 13 patients (10%) were in the very preterm group, 44 patients (9%) were in the late and moderate preterm group, and 36 patients (4%) were in the term group. Hemoglobin predicted PPH in all gestational age groups. Platelet count was associated with PPH in term, but not in preterm patients. Fibrinogen was associated with PPH in late prematurity but not in term patients and not in patients with early or extreme prematurity. Conclusions: Antepartum hemoglobin was the only factor predicting PPH in preterm and term caesarean sections. Platelet count and fibrinogen concentration were associated with PPH in term and late prematurity, respectively, but not in earlier stages of prematurity. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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<p>STROBE flowchart.</p>
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<p>Incidence of postpartum hemorrhage decreases with gestational age.</p>
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15 pages, 3938 KiB  
Article
Whole Blood Transcriptome Analysis in Congenital Anemia Patients
by Maria Sanchez-Villalobos, Eulalia Campos Baños, Elena Martínez-Balsalobre, Veronica Navarro-Ramirez, María Asunción Beltrán Videla, Miriam Pinilla, Encarna Guillén-Navarro, Eduardo Salido-Fierrez and Ana Belén Pérez-Oliva
Int. J. Mol. Sci. 2024, 25(21), 11706; https://doi.org/10.3390/ijms252111706 - 31 Oct 2024
Viewed by 409
Abstract
Congenital anemias include a broad range of disorders marked by inherent abnormalities in red blood cells. These abnormalities include enzymatic, membrane, and congenital defects in erythropoiesis, as well as hemoglobinopathies such as sickle cell disease and thalassemia. These conditions range in presentation from [...] Read more.
Congenital anemias include a broad range of disorders marked by inherent abnormalities in red blood cells. These abnormalities include enzymatic, membrane, and congenital defects in erythropoiesis, as well as hemoglobinopathies such as sickle cell disease and thalassemia. These conditions range in presentation from asymptomatic cases to those requiring frequent blood transfusions, exhibiting phenotypic heterogeneity and different degrees of severity. Despite understanding their different etiologies, all of them have a common pathophysiological origin with congenital defects of erythropoiesis. We can find different types, from congenital sideroblastic anemia (CSA), which is a bone marrow failure anemia, to hemoglobinopathies as sickle cell disease and thalassemia, with a higher prevalence and clinical impact. Recent efforts have focused on understanding erythropoiesis dysfunction in these anemias but, so far, deep gene sequencing analysis comparing all of them has not been performed. Our study used Quant 3′ mRNA-Sequencing to compare transcriptomic profiles of four sickle cell disease patients, ten thalassemia patients, and one rare case of SLC25A38 CSA. Our results showed clear differentiated gene map expressions in all of them with respect to healthy controls. Our study reveals that genes related to metabolic processes, membrane genes, and erythropoiesis are upregulated with respect to healthy controls in all pathologies studied except in the SLC25A38 CSA patient, who shows a unique gene expression pattern compared to the rest of the congenital anemias studied. Our analysis is the first that compares gene expression patterns across different congenital anemias to provide a broad spectrum of genes that could have clinical relevance in these pathologies. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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<p>QuantSeq analysis in different congenital anemias. (<b>A</b>) General scheme of Quant 3′ mRNA–Sequencing procedure. (<b>B</b>–<b>E</b>) Heatmap and pie chart showing under- (blue) or overexpressed (red) genes between controls and transfusion-dependent thalassemia (TDT) (<b>B</b>), non-transfusion-dependent thalassemia (NTDT), (<b>C</b>), sickle cell disease (SCD), (<b>D</b>) and congenital sideroblastic anemia (CSA) patient. Heatmap is restricted to significant data according to Log2FC &lt; −2 or &gt;2, and adjusted <span class="html-italic">p</span>–value &lt; 0.05.</p>
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<p>The CSA patient exhibits a distinct expression pattern in genes with respect to the rest of the congenital anemias. Heatmaps showing genes, which are significantly underexpressed (blue) or overexpressed (red) across different patient groups. The intensity of the colors indicates the level of expression of each representative gene. Groups studied correlate with those indicated in <a href="#ijms-25-11706-f001" class="html-fig">Figure 1</a> and pathways have been selected considering their importance in red blood cells, including erythropoiesis, iron metabolism, glycolysis, oxidative metabolism, and genes that codified erythrocyte membrane proteins.</p>
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<p>The CSA patient presents a different expression pattern of genes involved in erythropoiesis and iron metabolism. (<b>A</b>) Analysis of differential expressions of genes involved in erythropoiesis and heme group formation. Increase levels of <span class="html-italic">GATA1</span>, <span class="html-italic">HEMGN</span>, <span class="html-italic">ALAS2</span>, <span class="html-italic">SLC25A38</span>, <span class="html-italic">SLC25A37</span>, <span class="html-italic">ABCB10</span>, and <span class="html-italic">FECH</span> in all congenital anemias with respect to healthy control except the CSA patient. The increase in <span class="html-italic">ERFE</span> levels in all congenital anemias studied. (<b>B</b>) The <span class="html-italic">CDAN1</span> gene expression is significantly decreased in CSA patients. All graphs are represented in fold change with respect to control samples.</p>
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<p>BPGM gene expression correlates with SCD patients’ severity. (<b>A</b>) Graph with the representative fold change expression compared to healthy controls for the <span class="html-italic">BPGM</span> gene in TDT, NTDT, SCD, and CSA patients. (<b>B</b>) <span class="html-italic">BPGM</span> normalized gene expression in the 4 healthy controls and the 4 SCD patients, with a clear increase in <span class="html-italic">BPGM</span> gene expression in S2 and S4 patients that correlates with patients’ disease severity.</p>
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<p>A high expression gene profile related to oxidative metabolism in the majority of the congenital anemias compared to healthy donors. (<b>A</b>) Genes related to oxidative metabolism, <span class="html-italic">GLRX5, GPX1, GCLC</span>, and <span class="html-italic">PRDX2</span>, are upregulated in all congenital anemias with respect to healthy controls except in the CSA patient. (<b>B</b>) Significant fold change decrease in <span class="html-italic">SLC25A39</span> gene expression in the CSA patient. All graphs represent the fold change relative to healthy control individuals.</p>
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<p>The genes related to structural membrane protein expression are differentially expressed in the different congenital anemias. <span class="html-italic">SCL4A1, ANK1, EPB4.1, EPB4.2, SPTB, STOM</span> and <span class="html-italic">SPTA1</span> gene expression profiles are represented for TDT, NTDT, SCD, and CSA patients. A decrease in expression in all of these genes is observed in the CSA patient. All fold changes are relative to healthy control individuals.</p>
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<p>Dysregulated metabolic pathways in patients with congenital anemias (<b>A</b>–<b>E</b>). STRING analysis of interactions among upregulated genes in NTDT (<b>A</b>) and SCD (<b>C</b>) patients, and downregulated genes in NTDT (<b>B</b>), SCD (<b>D</b>), and CSA (<b>E</b>), compared to healthy controls. The table highlights metabolic pathways significantly impacted, accounting for the total number of genes involved in each network, their strength (Log10(genes implicated/total number of genes in the network)), and significance (<span class="html-italic">p</span>-values corrected for multiple testing within each category using the Benjamini–Hochberg procedure).</p>
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12 pages, 434 KiB  
Article
Risk Factor Analysis Including Inflammatory Markers for ICU Admission and Survival After Pneumonectomy
by Mediha Turktan, Ersel Gulec, Alper Avcı, Zehra Hatıpoglu and Ilker Unal
Medicina 2024, 60(11), 1768; https://doi.org/10.3390/medicina60111768 - 29 Oct 2024
Viewed by 393
Abstract
Background and Objectives: To assess the impact of preoperative inflammatory parameters on the necessity for intensive care unit (ICU) admission and survival after pneumonectomy. Materials and Methods: We enrolled 207 adult patients who underwent pneumonectomy between December 2016 and January 2022. We collected [...] Read more.
Background and Objectives: To assess the impact of preoperative inflammatory parameters on the necessity for intensive care unit (ICU) admission and survival after pneumonectomy. Materials and Methods: We enrolled 207 adult patients who underwent pneumonectomy between December 2016 and January 2022. We collected data from patients’ electronic medical records. Results: The preoperative albumin level was statistically lower, need for blood transfusion was higher, and length of hospital stay was longer in ICU-admitted patients (p = 0.017, p = 0.020, and p = 0.026, respectively). In multivariate analysis, intra-pericardial pneumonectomy and postoperative complications were predictive factors for ICU admission (OR = 3.46; 95%CI: 1.45–8.23; p = 0.005 and OR = 5.10; 95%CI: 2.21–11.79; p < 0.001, respectively). Sleeve or pericardial pneumonectomy (p = 0.010), intraoperative vascular injury (p = 0.003), the need for mechanical ventilation (p < 0.001), acute renal failure (p = 0.018), sepsis (p = 0.008), respiratory failure (p < 0.001), pneumonia (p = 0.025), the need for blood transfusion (p = 0.047), elevated blood urea nitrogen (BUN) (p = 0.046), and elevated creatinine levels (p = 0.004) were more common in patients who died within 28 days. Patients who died within 90 days exhibited higher preoperative neutrophil-to-lymphocyte ratio (NLR) values (p = 0.019) and serum creatinine levels (p = 0.008), had a greater prevalence of sleeve or intra-pericardial pneumonectomy (p = 0.002), the need for mechanical ventilation (p < 0.001), intraoperative vascular injury (p = 0.049), sepsis (p < 0.001), respiratory failure (p = 0.019), and contralateral pneumonia (p = 0.008) than those who did not. Conclusions: Intra-pericardial pneumonectomy and postoperative complications are independent predictors of ICU admission after pneumonectomy. Tracheal sleeve and intra-pericardial procedures, intraoperative and postoperative complications, the need for blood transfusion, preoperative NLR ratio, BUN and creatinine levels may also be potential risk factors for mortality. Full article
(This article belongs to the Section Surgery)
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<p>Flow diagram of the study.</p>
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13 pages, 2645 KiB  
Article
Quality of Life and Out-of-Pocket Expenditures for Sickle Cell Disease Patients in Saudi Arabia: A Single-Center Study
by Yazed AlRuthia, Rayan B. Alanazi, Sultan F. Alotaibi and Miteb Alanazi
Healthcare 2024, 12(21), 2146; https://doi.org/10.3390/healthcare12212146 - 29 Oct 2024
Viewed by 642
Abstract
Background: Sickle cell anemia (SCD) is a relatively uncommon health condition in many countries, but it is prevalent in Saudi Arabia mainly due to the high incidence of consanguineous marriages. Regrettably, there are elevated rates of vaso-occlusive crises (VOCs) and blood transfusions, leading [...] Read more.
Background: Sickle cell anemia (SCD) is a relatively uncommon health condition in many countries, but it is prevalent in Saudi Arabia mainly due to the high incidence of consanguineous marriages. Regrettably, there are elevated rates of vaso-occlusive crises (VOCs) and blood transfusions, leading to poor quality of life and significant financial strain. Objective(s): This study aimed to assess the frequency of blood transfusions, out-of-pocket expenditures (OOPEs), and health-related quality of life (HRQoL) in SCD patients. Methods: This was a questionnaire-based cross-sectional study that involved SCD patients at a university-affiliated tertiary care center in Riyadh, Saudi Arabia. The patients’ medical and sociodemographic characteristics were obtained from the electronic medical records. Data on HRQoL and OOPEs were collected through a questionnaire-based interview. To present the baseline characteristics, descriptive statistics such as mean, standard deviation, frequency, and percentage were used. In addition, various statistical tests, including the Chi-Square test, Student t-test, one-way ANOVA, and multiple linear regression, were performed. Results: One hundred and eighteen patients consented to participate and were included in the analysis. Almost 53% of the patients were females. The mean age of the sample was 31 years, while the age-adjusted quality-adjusted life years (QALYs) was 24.33 years (p-value < 0.0001). Most patients (83.05%) reside in Riyadh with a monthly family income of less than USD 2666.67 (75.42%). Monthly OOPEs were, on average, USD 650.69 ± 1853.96, and one-third of the adult patients reported income loss due to illness, further exacerbating their financial strain. High frequency of blood transfusion (β = −0.0564, p-value = 0.0066) and higher number of comorbidities (β = −0.10367, p-value = 0.0244) were negatively associated with the HRQoL among adult patients. On the other hand, adult patients with higher levels of education had better HRQoL (β = 0.05378, p-value = 0.0377). Conclusions: The findings of this study highlight the negative impact of SCD on patients’ HRQoL and financial well-being. This underscores the urgent need for comprehensive systemic approaches to address the challenges posed by SCD in Saudi Arabia. Full article
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<p>Out-of-pocket expenditures (OOPE) for travel and accommodation among patients outside Riyadh city.</p>
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<p>Financial stress feeling among adult patients stratified by individual monthly income.</p>
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<p>Impact of SCD on adult patients’ careers.</p>
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<p>Mean scores of the EuroQol-5D-5L Visual Analog Scale (VAS) among male and female patients.</p>
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<p>Age and age-adjusted QALYs among male and female patients.</p>
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16 pages, 2544 KiB  
Article
Monitoring Cell Activation and Extracellular Vesicle Generation in Platelet Concentrates for Transfusion
by Ana Kolenc, Maja Grundner, Irma Hostnik and Elvira Maličev
Int. J. Mol. Sci. 2024, 25(21), 11577; https://doi.org/10.3390/ijms252111577 - 28 Oct 2024
Viewed by 551
Abstract
Platelets play a crucial role in blood transfusions, and understanding the changes that occur during their storage is important for maintaining the quality of preparations. In this study, we examined key alternating factors, with a particular focus on platelet activation and the release [...] Read more.
Platelets play a crucial role in blood transfusions, and understanding the changes that occur during their storage is important for maintaining the quality of preparations. In this study, we examined key alternating factors, with a particular focus on platelet activation and the release of extracellular vesicles. Additionally, we compared two detection methods—imaging flow cytometry (IFC) and nanoparticle tracking analysis (NTA)—for their effectiveness in detecting particles. Platelet concentrates were prepared by pooling buffy coats from five blood group-compatible donors in an additive solution. Samples were analysed after one, three, and seven days of storage for residual white blood cells (WBCs), glucose levels, platelet activation, and extracellular vesicle concentrations. Over the storage period, the total platelet concentration decreased slightly, while the residual WBC count remained stable. Glucose levels declined, whereas platelet activation and extracellular vesicle concentration increased, with a positive correlation between the two. The particle size remained relatively unchanged throughout the storage period. Ultimately, despite controlled processing and storage conditions, platelet activation, and the release of extracellular vesicles still occurred, which may have implications for transfusion recipients. Although an optimised method is still needed, IFC has proved to be specific and potentially appropriate for detecting extracellular vesicles in transfusion preparations. Full article
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<p>Platelet concentration in stored platelet concentrates on days 1, 3, and 7 after pooling. The figure shows individual measurements and average values with standard deviation of three independent experiments.</p>
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<p>Concentration of residual white blood cells at different time points. Figure shows individual measurements and average values with standard deviation of three independent experiments.</p>
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<p>(<b>A</b>) Concentration of glucose at different time points. Figure shows individual measurements and average value with standard deviation of three independent experiments. Statistical difference is indicated with asterisks, **** <span class="html-italic">p</span> &lt; 0.0001. (<b>B</b>) Correlation between glucose concentration and platelet activation. Figure represents the percentage of activated platelets compared to glucose concentration analysed using the Pearson Correlation and Student’s <span class="html-italic">t</span>-test (n = 44). An r value of 0.72 indicates a significant correlation with <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>The percentage of activated platelets, identified by the presence of P-selectin on their surface, over a storage period of seven days. The figure shows individual measurements and average values with a standard deviation of three independent experiments. Statistical difference is indicated with asterisks, *** <span class="html-italic">p</span> &lt; 0.001 and **** <span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>The gating strategy used on the FACSCalibur flow cytometer to determine the percentage of activated platelets (CD62P) among the total platelet population (CD61). Initially, platelets were gated based on their characteristic forward scatter (FSC) and side scatter (SSC) properties.</p>
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<p>Results of analysis using ImageStream Imaging Flow Cytometer. (<b>A</b>) Concentration of extracellular vesicles over the storage time of platelet preparations. The figure shows individual measurements and average values with a standard deviation of three independent experiments. Statistical difference is indicated with asterisks, **** <span class="html-italic">p</span> &lt; 0.0001. (<b>B</b>) Examples of CD9-positive events from days 1, 3, and 7 samples that correlate with events on respective scatterplots. (<b>C</b>) Gating strategy for the final positive results after excluding coincidence events and multiple events, along with events with high SSC. All the used controls and calibration beads are also included. (<b>D</b>) Examples of small and large fluorescent calibration bead populations used for the initial acquisition gate. (<b>E</b>) Examples of multiple events excluded from the analysis with appropriate masks and features of IDEAS software (Version 6.3).</p>
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<p>The concentration of extracellular vesicles, as measured by the NTA. The figure shows individual measurements and average values with a standard deviation of three independent experiments. Statistical difference is indicated with asterisks, ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>The size of extracellular vesicles according to NTA. (<b>A</b>) Figure shows individual measurements and average values with standard deviation of three independent experiments. (<b>B</b>) Example of the size distribution of extracellular vesicles of individual sample on days 1, 3, and 7.</p>
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<p>Correlation between the concentration of extracellular vesicles and platelet activation on ImageStream IFC (<b>A</b>) and NTA (<b>B</b>). The figure represents the percentage of activated platelets compared to the percentage of activated platelets analysed using the Pearson Correlation and Student’s <span class="html-italic">t</span>-test (n = 44 for A and n = 18 for B).</p>
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<p>The concentration of extracellular vesicles measured by IFC and NTA. The correlation between the two methods was analysed using the Pearson Correlation and Student’s <span class="html-italic">t</span>-test (n = 18). An r value of 0.78 indicates a significant correlation with <span class="html-italic">p</span> &lt; 0.001.</p>
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<p>Study design.</p>
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10 pages, 826 KiB  
Article
Autologous Blood Donation and Transfusion in Patients with Placental Malposition: A Single-Institution Pilot Study and Systematic Literature Review
by Iiji Koh, Kaoru Kawasaki, Kaori Moriuchi, Reona Shiro, Yoshie Yo and Noriomi Matsumura
Healthcare 2024, 12(21), 2138; https://doi.org/10.3390/healthcare12212138 - 27 Oct 2024
Viewed by 533
Abstract
Background: Autologous blood donation for placental malposition is common in Japan, but no studies have scientifically evaluated its usefulness. The purpose of this study was to evaluate the necessity for autologous blood donation for placental malposition. Methods: A retrospective study was conducted of [...] Read more.
Background: Autologous blood donation for placental malposition is common in Japan, but no studies have scientifically evaluated its usefulness. The purpose of this study was to evaluate the necessity for autologous blood donation for placental malposition. Methods: A retrospective study was conducted of patients who underwent autologous blood donation for placental malposition at Kindai University Hospital from 2012 to 2022. The primary outcome was the proportion of patients who were able to avoid allogeneic blood transfusion by autologous blood transfusion; secondary outcomes were autologous blood disposal rate, allogeneic blood transfusion rate, and complications of autologous blood donation and allogeneic blood transfusion. A systematic review of studies on autologous blood transfusion for placental malposition was conducted on PubMed. Results: Fifty-two patients (total placenta previa 16; marginal placenta previa 20; low-lying placenta 16) were included. Eight (15%) had complications at the time of autologous blood donation, including non-reassuring fetal heart rate, but no sequelae. Allogeneic blood transfusion was avoided by autologous blood transfusion in only five cases (9.6%). Autologous blood was discarded in nine cases (17%), seven of which had a low-lying placenta positioned normally at delivery. Allogeneic blood transfusion was performed in eight cases (15%) with no complications. In the systematic review, seven articles that met the inclusion criteria were selected for further evaluation. The results showed that there were no publications that scientifically demonstrated the benefit of autologous blood transfusion. Conclusions: The results of this study indicate that autologous blood donation for placental malposition has little benefit. Full article
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<p>Outcome of 52 patients who underwent autologous blood donation for placental malposition. (<b>A</b>) Heat map presentation of individual cases. Placenta: position of placenta; total: total anterior placenta; marginal: marginal anterior placenta; low-lying: low-lying placenta. C/S: cesarean section; allo: allogeneic transfusion; auto: autologous transfusion; discarded: autologous blood was discarded. A shaded line in the box indicates that autologous blood was partially discarded. (<b>B</b>) Blood loss during delivery.</p>
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<p>Selection process for studies according to the PRISMA flow diagram.</p>
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10 pages, 614 KiB  
Article
Radiation-Induced Hemorrhagic Cystitis in Prostate Cancer Survivors: The Hidden Toll
by René Gatsinga, Benjamin J. H. Lim, Navin Kumar, Jacinda G. G. Tan, Youquan Li, Michael L. C. Wang, Terence W. K. Tan, Jeffrey K. L. Tuan, Yu Guang Tan, Kenneth Chen and John S. P. Yuen
Medicina 2024, 60(11), 1746; https://doi.org/10.3390/medicina60111746 - 24 Oct 2024
Viewed by 414
Abstract
Background and Objectives: Radiation therapy (RT) plays a crucial role in managing prostate cancer, offering effective disease control and improving survival rates in both localized and recurrent cases. However, RT can lead to hemorrhagic cystitis, a significant late complication resulting in chronic morbidity [...] Read more.
Background and Objectives: Radiation therapy (RT) plays a crucial role in managing prostate cancer, offering effective disease control and improving survival rates in both localized and recurrent cases. However, RT can lead to hemorrhagic cystitis, a significant late complication resulting in chronic morbidity and other health issues. This study aims to evaluate the real-world incidence of radiation-induced hemorrhagic cystitis requiring surgical intervention. Materials and Methods: This retrospective cohort study analyzed data from prostate cancer survivors treated for hematuria at our center between January 2014 and January 2024. Patients were included if cystoscopy identified radiation cystitis as the cause of hematuria. Descriptive statistics were used, and binomial logistic regression analyses with univariate and multivariate analysis were performed to identify risk factors for worse outcomes. Results: Fifty-two patients met the inclusion criteria. The estimated cumulative incidence at a median follow-up of 5.3 years was 4.5%. Among the participants, 21.2% required more than two transurethral bladder fulguration (TUBF) procedures, and 38.5% needed more than two hospital admissions for hematuria management. The median time to the first fulguration was 64 months. Blood transfusions were necessary in 53.8% of cases, and 38.5% required hyperbaric oxygen therapy. Ultimately, 5.8% of the patients underwent cystectomy. Univariate analysis identified ischemic heart disease (IHD) and antiplatelet therapy as significant risk factors (OR: 5.17 and 5.18, respectively), along with longer time to first fulguration (OR: 5.02). Multivariate analysis confirmed antiplatelet therapy (OR: 2.8, p = 0.05) and time to first TUBF (OR: 1.8, p = 0.02) as significant predictors of multiple procedures. Conclusions: Radiation cystitis remains a significant burden on prostate cancer survivors. Patients on antithrombotic agents, those with delayed initial presentations, and those who received radiation as salvage therapy are more likely to experience higher morbidity. Full article
(This article belongs to the Section Urology & Nephrology)
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<p>Number of patients treated for prostate cancer per year.</p>
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<p>New cases of RHC requiring surgical intervention annually.</p>
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