Changes In Hematocrit Research Articles

Utilization and safety of off-label prothrombin complex concentrate (four-factor prothrombin complex concentrate) in a surgical population.

The aim of this study is to evaluate and describe the utilization and safety of 4F-PCC in a nonanticoagulated, surgical patient population at an academic, tertiary care center. This retrospective, single-center chart review evaluated nonanticoagulated adult patients at least 18 years of age who had at least one dose of 4F-PCC administered between 1 January 2017 and 30 September 2022 for a surgical or peri-procedural indication. Hemostatic efficacy following 4F-PCC administration was the primary outcome, assessed by subsequent blood product administration and hemoglobin and hematocrit reduction. Secondary outcomes included an assessment of thrombotic events within 30 days post-4F-PCC administration, in-hospital mortality, and the length of hospital stay. A total of 71 patients met the inclusion criteria, with 61 patients receiving 4F-PCC for cardiac surgery and 10 patients for other intraoperative or peri-procedural indications. The mean total 4F-PCC dose was 25.0 U/kg. For the primary outcome of hemostatic efficacy, 81% of patients had excellent hemostasis; however, blood product administration was reported in 95.8% of patients post-4F-PCC. Thromboembolic events occurred in 10 (14.1%) patients and 21.1% of patients expired prior to discharge in the total cohort. Off-label 4F-PCC use in nonanticoagulated patients is reported despite a lack of robust guidance for use. Following 4F-PCC administration, hemostatic efficacy based on hemoglobin and hematocrit changes was observed; however, blood product use was frequent, and 4F-PCC administration was not without risks, including thromboembolic complications such deep vein thrombosis (DVT), pulmonary embolism, and stroke. Further studies are needed to validate the off-label administration of 4F-PCC in nonanticoagulated patients.

Hemodynamic regulation allows stable growth of microvascular networks

How do vessels find optimal radii? Capillaries are known to adapt their radii to maintain the shear stress of blood flow at the vessel wall at a set point, yet models of adaptation purely based on average shear stress have not been able to produce complex loopy networks that resemble real microvascular systems. For narrow vessels where red blood cells travel in a single file, the shear stress on vessel endothelium peaks sharply when a red blood cell passes through. We show that stable shear-stress-based adaptation is possible if vessel shear stress set points are cued to the stress peaks. Model networks that respond to peak stresses alone can quantitatively reproduce the observed zebrafish trunk microcirculation, including its adaptive trajectory when hematocrit changes or parts of the network are amputated. Our work reveals the potential for mechanotransduction alone to generate stable hydraulically tuned microvascular networks.

Erythropoiesis and estimated fluid volume regulation following initiation of ipragliflozin treatment in patients with type 2 diabetes mellitus and chronic kidney disease: A post-hoc analysis of the PROCEED trial.

To analyse the changes in erythropoietic and estimated fluid volume parameters after the initiation of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). This was a post-hoc analysis of the PROCEED trial, which evaluated the effect of 24-week ipragliflozin treatment on endothelial dysfunction in patients with T2DM and CKD. We evaluated the changes in erythropoietic and estimated fluid volume parameters from baseline to 24 weeks post-treatment in 53 patients who received ipragliflozin (ipragliflozin group) and 55 patients with T2DM and CKD without sodium-glucose co-transporter 2 inhibitors (control group), a full analysis set of the PROCEED trial. The increases in haemoglobin [estimated group difference, 0.5 g/dl; 95% confidence interval (CI), 0.3-0.8; p < .001], haematocrit (estimated group difference, 2.2%; 95% CI, 1.3-3.1; p < .001) and erythropoietin (estimated log-transformed group difference, 0.1; 95% CI, 0.01-0.3; p = .036) were significantly greater in the ipragliflozin group than those in the control group. Ipragliflozin treatment was significantly associated with an increase in erythropoietin, independent of the corresponding change in haemoglobin (β = 0.253, p < .001) or haematocrit (β = 0.278, p < .001). Reductions in estimated plasma volume (estimated group difference, -7.94%; 95% CI, -11.6 to -4.26%; p < .001) and estimated extracellular volume (estimated group difference, -181.6 ml; 95% CI, -275.7 to -87.48 ml; p < .001) were significantly greater in the ipragliflozin group than those in the control group. Erythropoiesis was enhanced and estimated fluid volumes were reduced by ipragliflozin in patients with T2DM and CKD. PROCEED trial (registration number: jRCTs071190054).

(094) Safety and Efficacy of Enclomiphene Compared to Clomiphene for Hypogonadal Men

Abstract Introduction Clomiphene, and its trans isomer enclomiphene, have been used off-label in recent years for hypogonadal men seeking to maintain fertility. Both drugs have become increasingly widespread within andrology clinics; thus, understanding the comparative benefits and risks of these medications are crucial for optimizing treatment decisions and providing improved therapeutic options. Objective To investigate the longitudinal benefits and risks associated with enclomiphene compared to clomiphene to provide valuable insights for clinicians when making treatment decisions in the management of hypogonadism and male fertility preservation. Methods We retrospectively studied patients who had been prescribed clomiphene, and later enclomiphene, at a university hospital within the observation range of 1/1/2021-12/31/2022, encompassing 66 patients. All included patients were prescribed clomiphene prior to switching to enclomiphene. Baseline laboratory values for each patient prior to being prescribed clomiphene were documented, followed by subsequent values for each of these variables in the most recent visit prior to stopping clomiphene as well as any noted adverse effects experienced during this time. Laboratory values and adverse effects were noted for the same patients in their most recent visit while taking enclomiphene. Adverse events were defined by 1) depressive thoughts; 2) weak muscle strength; 3) gynecomastia; 4) mood changes; or 5) agitation as well as changes in estradiol and hematocrit laboratory values. Two-tailed T-Tests were employed using SPSS to analyze the longitudinal impacts of clomiphene and enclomiphene on serum hormone values. Results In our cohort, men on clomiphene experienced any adverse events 18.18% of the time, whereas men on enclomiphene experienced any adverse events 3.45% of the time. From our data, men on enclomiphene had statistically lower rates of documented adverse events than the same men on clomiphene, indicating no increased risk on the newer drug; neither treatment yielded any serious adverse events. In looking specifically at hormone-related adverse events, estradiol increased significantly on clomiphene but not on enclomiphene (17.25 versus -0.29 pg/mL; t=4.271, p=.00005). However, there was no difference in change in hematocrit between the two medications (0.10% versus 0.79% increase; t=-1.103, p=.314). On average, testosterone increased 149.33 ng/dL from their baseline scores while on clomiphene and increased 108.55 ng/dL from their clomiphene values while on enclomiphene. When comparing the improvement of testosterone values attributed to clomiphene versus enclomiphene, the change of testosterone levels over time attributed to either medication are not statistically different (t-value = .883; p-value = .379). Lastly, men stayed on clomiphene for an average of 32.92 months before switching to enclomiphene. Conclusions Our findings show that enclomiphene provides the same magnitude of improvement in testosterone but through safer means, as noted by its lower rate of documented adverse events. These findings support the use of enclomiphene as a comparable treatment option for hypogonadal men while minimizing the risk of adverse effects. Further research and larger studies are warranted to validate these conclusions and explore additional long-term effects of enclomiphene. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Larry Lipshultz: AbbVie (Consultant) American Medical Systems/Boston Scientific (Speaker) Augmenta LLC (Stockholder) Aytu BioScience (Consultant) Contraline, Inc. (Consultant) Endo Pharmaceuticals (Consultant/Speaker) Inherent Biosciences (Advisor) Lipocine (Consultant); Mohit Khera: Consultant- AbbVie, Halozyme, Clarus, Metuchen, Acerus, Boston Scientific, Coloplast, Endo.

Comparing visual estimation and hematocrit change in the assessment of blood loss among women undergoing cesarean delivery in a tertiary facility in northern Uganda.

Cesarean section poses a fourfold risk for postpartum hemorrhage (PPH), necessitating accurate blood loss estimation to enable timely interventions. However, the conventional visual estimation method often leads to underestimation, resulting in undiagnosed PPH even in our setting, Uganda. Yet, the quantitative standard techniques remain underutilized. We compared visual and calculated blood loss among women undergoing cesarean delivery at Gulu Regional Referral Hospital in northern Uganda. We employed a cross-sectional study design. We enrolled pregnant women scheduled for cesarean section and determined both calculated and visually estimated blood loss. Data analysis involved using Pearson's moment correlation coefficient to compare the two methods and logistic regression to determine the factors associated with PPH. We included 105 participants, most were primigravida (n = 100, 43%), aged 15-24 years (n = 100, 52%), with term gestation (n = 100, 75%). The mean visual estimated blood loss (vEBL) was 235.3 ± 123.7 ml (interquartile range (IQR) 50-600 ml), while the calculated estimated blood loss (cEBL) was 435.0 ± 1328.2 ml (IQR -11,182.1-2226.7 ml). Visual estimation underestimated blood loss in 90% of cases (n = 100), and 21% (n = 21) had undiagnosed PPH (>1000 ml blood loss). None of the respondents had PPH (>1000 ml blood loss) following vEBL. There was a small positive correlation between both methods (vEBL and cEBL; r = 0.1165; p = 0.2482). Women aged >35 years were 1.60 times more likely to experience PPH than their counterparts aged 25-34 years (adjusted odds ratio (AOR): 1.60; 95% CI: 1.11-2.30, p < 0.011). Chorioamnionitis increased the risk of PPH by 2.2 times (AOR: 2.20; 95% CI: 1.20-4.05, p < 0.012). The visual estimation technique significantly underestimated blood loss in up to 90% of cases, particularly during emergency cesarean sections. Among the 21% of cases diagnosed with PPH based on calculated blood loss, advanced maternal age and chorioamnionitis were notable contributing factors. Routine hemoglobin and hematocrit testing in obstetric care can be effectively utilized to objectively assess blood loss, aiding in the accurate diagnosis and management of PPH. Implementing these measures, even in resource-constrained settings, can significantly reduce the morbidity and mortality associated with PPH. Not applicable.

Impacts of temperature and turbidity on the gill physiology of darter species

Fish gills are complex organs that have direct contact with the environment and perform numerous functions including gas exchange and ion regulation. Determining if gill morphometry can change under different environmental conditions to maintain and/or improve gas exchange and ion regulation is important for understanding if gill plasticity can improve survival with increasing environmental change. We assessed gill morphology (gas exchange and ion regulation metrics), hematocrit and gill Na+/K+ ATPase activity of wild-captured blackside darter (Percina maculata), greenside darter (Etheostoma blennioides), and johnny darter (Etheostoma nigrum) at two temperatures (10 and 25 °C) and turbidity levels (8 and 94 NTU). Samples were collected August and October 2020 in the Grand River to assess temperature differences, and August 2020 in the Thames River to assess turbidity differences. Significant effects of temperature and/or turbidity only impacted ionocyte number, lamellae width, and hematocrit. An increase in temperature decreased ionocyte number while an increase in turbidity increased lamellae width. Hematocrit had a species-specific response for both temperature and turbidity. Findings suggest that the three darter species have limited plasticity in gill morphology, with no observed compensatory changes in hematocrit or Na+/K+ ATPase activity to maintain homeostasis under the different environmental conditions.

Intravenous versus intramuscular oxytocin injection for preventing uterine atonic primary postpartum haemorrhage in third stage of labour: A double-blind randomised controlled trial.

To compare the efficacy and safety of intravenous and intramuscular oxytocin in preventing atonic primary postpartum haemorrhage in the third stage of labour. A double-blind randomised clinical study on consenting women without risk factors for primary postpartum haemorrhage in labour at term. Two hundred and thirty-two women were randomly allotted into intravenous (n = 115) and intramuscular (n = 117) oxytocin groups in the active management of the third stage of labour. All participants received 10 IU of oxytocin, either IV or IM, and 1 ml of water for injection as a placebo via a route alternate to that of administration of oxytocin within 1 min of the baby's delivery. The primary outcome measures were mean postpartum blood loss and haematocrit change. Trial Registration No.: PACTR201902721929705. The baseline socio-demographic and clinical characteristics were similar between the two groups (p > 0.05). There was no statistically significant difference between the two groups with regards to the mean postpartum blood loss (254.17 ± 34.85 ml versus 249.4 ± 39.88 ml; p = 0.210), haematocrit change (2.4 (0.8%) versus 2.1 (0.6%); p = 0.412) or adverse effects (p > 0.05). However, the use of additional uterotonics was significantly higher in the intravenous group (25 (21.73%) versus 17 (14.53%); p = 0.032). Although oxytocin in both study groups showed similar efficacy in terms of preventing atonic primary postpartum haemorrhage, participants who received intravenous oxytocin were more likely to require additional uterotonics to reduce their likelihood of having an atonic primary postpartum haemorrhage. However, both routes have similar side effect profiles.

Patient Satisfaction with Oral Testosterone Undecanoate in Men Who Received Prior Testosterone Therapy: An Open-Label, Single-Center Clinical Trial.

To evaluate patient satisfaction and symptom control in hypogonadal men transitioning from other testosterone therapies to oral testosterone undecanoate (TU). In this open-label clinical trial, men aged 18 to 75 years with hypogonadism were switched to oral TU after a sufficient washout of previous testosterone therapies. Treatment satisfaction and symptom control were primarily measured using the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) and quantitative androgen deficiency in aging males (qADAM) questionnaires, respectively. Secondary outcomes included changes in serum testosterone (T), estradiol (E2), hematocrit (HCT), and prostate-specific antigen (PSA) levels. Forty-one men participated, with significant improvements in all TSQM-9 scores observed over 6 months. Symptom control as measured by qADAM remained consistent. There was a significant increase in serum T and E2 levels, but HCT and PSA levels remained stable. Switching to oral TU from other testosterone therapies is associated with increased patient satisfaction and stable hypogonadal symptom control.

A retrospective analysis of the clinical efficacy of pancreatic duct stent implantation in the management of acute biliary pancreatitis requiring ERCP

BackgroundThis study aimed to investigate the feasibility, effectiveness, and safety of pancreatic duct stenting in managing acute biliary pancreatitis (ABP) necessitating endoscopic retrograde cholangiopancreatography (ERCP). It further aimed to provide valuable insights for subsequent clinical diagnosis and treatment.MethodsThis research employs an observational retrospective case–control study design, encompassing patients with ABP who underwent ERCP at the hepatobiliary surgery department of the General Hospital of Ningxia Medical University between August 1, 2018, and December 31, 2020. A total of 229 cases were screened based on inclusion and exclusion criteria. Regardless of ABP severity, patients were categorized into the stent group (141) and the non-stent group (88). Changes in blood amylase (Amy), lipase (LIP), leukocyte count (WBC), total bilirubin (TBIL), alanine aminotransferase (ALT), hematocrit (HCT), and creatinine (CR) were compared between the two groups. Moreover, variables such as recovery time for oral feeding, hospitalization duration, hospitalization costs, local complications, systemic complications, and new organ failure were recorded to assess the therapeutic effect of pancreatic duct stenting.ResultsNo significant differences were observed in gender, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, ABP severity grade, organ failure (OF), cholangitis, or biliary obstruction between the pancreatic stent and non-stent groups (P > 0.05). There was no significant difference in the incidence of complications related to acute pancreatitis between the two groups (P > 0.05). The median fasting and hospitalization times of patients in the stent group were significantly shorter than those in the non-stent group (P < 0.05). No significant differences between the groups were observed in hospitalization costs and in-hospital mortality (P > 0.05). There were no significant variations in white blood cell (WBC) count, TBIL, ALT, and creatinine (Cr) at admission, 72 h, and in the differences between the two groups (P > 0.05). The levels of Amy at admission and 72 h in the stent group were significantly higher than those in the non-stent group (P < 0.05). The differences in LIP and HCT in the stent group were considerably higher than in the non-stent group (P < 0.05). Although no significant differences were observed in mean Amy and LIP between the two groups (P > 0.05), the mean 72-h HCT in the stent group was 38.39% (95% confidence interval [CI] 37.82%–38.96%) was lower than that in the non-stent group (39.44%, 95% CI 38.70–40.17%) (P < 0.05).ConclusionIn the stent group, feeding time and hospital stay were significantly shorter than those in the non-stent group. No significant differences were observed between the two groups in the incidence of complications and mortality. The HCT value decreased more rapidly in the stent group. Early pancreatic stent implantation demonstrated the potential to shorten the eating and hospitalization duration of patients with ABP, facilitating their prompt recovery.Trial Registration: This study was registered as a single-center, retrospective case series (ChiCTR1800019734) at chictr.org.cn.

Biliverdin Reductase B Protects Against Primaquine Induced Hemolysis - Identification of a Novel Anti-Oxidant Pathway in Murine Erythrocytes

Background: Biliverdin Reductase B (BlvrB) is the fourth most abundant enzyme in red blood cells (RBCs) and is widely expressed in other tissues. In normal heme catabolism, porphyrin is converted to biliverdin-alpha (by hemoxygenase (HO)) and then reduced to bilirubin-alpha (by biliverdin reductase A (BlvrA)). Bilirubin-alpha is then glucuronidated and excreted. The large body of literature investigating heme metabolism, bilirubin-based pathologies, and the oxidative biology of bilirubin/biliverdin in adults focuses almost exclusively on BlvrA and the alpha isomers of biliverdin and bilirubin. However, porphyrin is a tetrapyrrole with 4 distinct meso-carbon bridges, each of which can be broken to generate a distinct biliverdin isomer (alpha, beta, gamma, or delta). Although HO is exquisitely specific for the alpha-bond (generating only biliverdin-alpha), chemical coupled oxidation of heme yields all four biliverdin isomers. BlvrB (and not BlvrA) can reduce each of non-alpha biliverdin isomers into their corresponding bilirubin isomers (bilirubin-beta is prevalent in neonatal jaundice and kernicterus). BlvrB also reduces flavins and additional quinone metabolites. Despite BlvrB's abundance and evolutionary conservation, its only known function is a subtle effect on hematopoietic lineage fate (megakaryocyte vs. erythroid). BlvrB has no known function in mature RBCs. We hypothesized that BlvrB plays an important antioxidant role that would only become obvious when other redundant anti-oxidant pathways were limited. Methods: A novel BlvrB knockout mouse was generated on a C57BL/6 background. A model of primaquine (PQ) induced oxidative hemolytic anemia in G6PD deficient mice was used as a clinically relevant scenario in which compromised antioxidant biology leads to treatment limiting pharmacotoxicity in RBCs. BlvrB-KO mice were crossed with two strains of mice that had murine G6PD replaced with either the A- deficient variant of human G6PD (hG6PD(A-)) or the non-deficient form of human G6PD (hG6PD(ND)). Four mouse strains (i.e., hG6PD(ND) and hG6PD(A-) mice with or without BlvrB deletion) received either a 4-day course of PQ or control PBS injections. Anemia was monitored by hematocrit (HCT). Reticulocyte count (RET) was monitored by flow cytometry as CD71+, thiazole orange+ erythrocytes. Peripheral blood was subjected to high resolution metabolomics to elucidate biochemical changes. Results: All mouse strains were healthy at baseline, with normal measured hematological parameters (i.e., Hct 40, RET 1.5%). No change in HCT or RET was observed in hG6PD(ND) or BlvrB-KOxhG6PD(ND) mice receiving PQ or in any strain receiving PBS. PQ induced hemolytic anemia in hG6PD(A-) mice, with an average HCT of 32.7 (18% drop) with RET of 3.1%. A significant exacerbation of PQ induced hemolysis was observed in BlvrB-KOxhG6PD(A-) mice that had an average HCT of 22.5 (44% drop) with RET of 5.3%. (n= 11 mice per group, p &amp;lt;0.001 between groups). Blood from PQ-treated hG6PD(A-)xBlvrBKO mice showed defective glycolysis at the level of glyceraldehyde 3-phosphate dehydrogenase, increased levels of multiple long-chain acylcarnitines, altered redox metabolism, and specific increases of hypoxanthine and sphingosine-1-phosphate (S1P). Three separate experiments were performed with similar results. Discussion: These data demonstrate that BlvrB deletion exacerbates oxidative injury and suggest that BlvrB provides a novel and hitherto undescribed antioxidant pathway in RBCs. Because approximately half a billion humans exhibit some form of G6PD deficiency, these data are also directly relevant to a large population of humans, which were modeled using hG6PD(A-) mice. These studies also define the metabolic lesion in peripheral blood. For example, GAPDH is well known to be highly sensitive to inactivation by oxidative damage, resulting in impaired glycolysis. Changes in hypoxanthine and S1P are known to be associated with decreased RBC function and survival. Finally, altered carnitine metabolism is associated with repair of lipid peroxidation in RBCs via the Lands Cycle. Although the mechanism by which BlvrB facilitates antioxidation is not yet clear, we hypothesize it involves redox cycling of non-alpha isomers of biliverdin and bilirubin. However, the mechanisms may be through reduction of flavins and/or other endogenous substrates. Ongoing studies are testing these hypotheses.

Erythrocytosis Is Rare With Exogenous Testosterone in Gender-Affirming Hormone Therapy.

Studies have found a variable incidence of erythrocytosis among people using testosterone as part of gender-affirming hormone therapy (GAHT). To examine the effect of using exogenous testosterone as GAHT on hematocrit in a large North American cohort. We conducted a cross-sectional analysis of testosterone and hematocrit laboratory values in 6670 patients who were prescribed testosterone through Plume, a national provider of GAHT. The prevalence of erythrocytosis, the mean hematocrit at predetermined testosterone thresholds and with varying routes of testosterone administration were assessed. Among 6670 individuals, 560 (8.4%) had a hematocrit ≥50%, 182 ≥ 52% (2.7%), and 60 ≥ 54% (0.9%). There was significant variation (P < .001) in hematocrit between different clinically relevant testosterone thresholds (T < 50 vs T 50-299 vs T 300-999 vs T ≥ 1000 ng/dL) and when comparing serum testosterone in increments of 50 ng/dL within the target range for males (300-1000 ng/dL) (P < .001). Mean hematocrit ranged from 41.84% (T < 50 ng/dL) to 45.68% (T 900-949 ng/dL). Patients on intramuscular testosterone had a higher mean hematocrit than those on transdermal testosterone (44.96% vs 43.41%, P < .001). Both route of administration (P < .001) and testosterone level (P < .001) had statistically significant associations with hematocrit when controlling for each other. While the magnitude of change in hematocrit with serum level and route of administration of testosterone was statistically significant, the absolute levels were within the normal range, unlikely to be clinically meaningful. These findings, along with the low prevalence of erythrocytosis, should help allay concerns about the use of testosterone as GAHT.

Blood-conserving and therapeutic efficacy of intravenous tranexamic acid at different time points after primary total knee arthroplasty with tourniquet application: a randomised controlled trial

BackgroundThe use of a tourniquet in combination with tranexamic acid (TXA) not only ensures clear vision, reduces intraoperative blood loss and shortens operative time but also improves cement-bone inter-digitation in total knee arthroplasty (TKA). However, there is no proof whether the blood flow blocking effect of tourniquet affects the antifibrinolytic effect of TXA, and the optimal timing of TXA administration is still unclear. Therefore, this study aims to investigate the effect of the first dose of TXA administered intravenously before tourniquet compression and release in TKA on perioperative blood loss and therapeutic efficacy in patients.MethodsIn this double-blind trial, 90 patients undergoing primary TKA were randomised into 2 groups: Group A, patients received intravenous TXA 10 min before tourniquet compression (20 mg/kg) and 3, 6 and 24 h later (10 mg/kg), and Group B, patients were treated the same as those in Group A but received intravenous TXA before tourniquet release. The primary outcomes were changes in blood loss, haemoglobin and haematocrit. Secondary outcomes included operation and tourniquet times, blood transfusion rate, subcutaneous petechiae and circumferential changes in the operated limb, visual analogue scale (VAS) score, hospital for special surgery (HSS) score, length of stay (LOS) postoperatively, complications and patient satisfaction.ResultsNo statistically significant difference was found between the 2 groups with regard to age, sex, weight, body mass index (BMI), Kellgren-Lawrence class, preoperative blood volume, preoperative laboratory values, operation and tourniquet times, transfusion rate, knee circumference, preoperative HSS, or VAS score (P:n.s.). There was no significant difference in intraoperative blood loss (IBL) (52.7 ml vs. 63.4 ml, P = 0.07), hidden blood loss (HBL) (91.4 ml vs. 119.9, P = 0.4) or total blood loss (TBL) (144.1 ml vs. 183.3 ml, P = 0.72) between Groups A and B. Haemoglobin, haematocrit and red blood cell count (RBC) dropped to a low point on postoperative day 3 and then rebounded, returning to normal levels on day 21, and the trend of change between the 2 groups was not statistically significant (P:n.s.). There was no significant difference in subcutaneous ecchymosis incidence, knee swelling rate, HSS score, VAS score, LOS postoperatively, complication rate or patient satisfaction (P:n.s.).ConclusionTXA was administered intravenously prior to tourniquet compression could effectively reduce blood loss in patients who had undergone total knee arthroplasty. However, there was no significant difference in knee swelling rate, subcutaneous bruising and petechiae incidence, knee function, complication rate or satisfaction between patients who TXA was given intravenously before tourniquet compression and release in primary TKA.

Assessing myocardial microvascular reactivity with a novel MRI imaging approach as an early biomarker of diabetic heart failure

Abstract Introduction Microvascular dysfunction (mvD), and more specifically coronary microvascular disease (CMD), has been implicated as the primary hallmark of diabetic cardiomyopathy and HFpEF, afflicting millions of people worldwide. The onset and progression of microvascular disease is driven by vascular inflammation and is characterized by vascular smooth muscle cell thickening and impaired vasomodulation, both of which ultimately reduce perfusion and damage tissue. To meet metabolic demands, the body recruits additional assistance from our microvascular reserve, which is diminished during stress, thus resulting in a dampened vasomodulatory response to stimuli. Diagnosing mvD in the myocardium, therefore, requires a non-invasive method to measure vasomodulation or, more precisely, changes in microvascular blood volume. Purpose Current clinical imaging platforms lack the ability to detect vasomodulation in a sensitive and specific manner. Because of this shortcoming, there is also no literature sex comparison of cardiac microvascular reactivity in response to stress in diabetics. This work aims to address this technology and knowledge gap by developing and demonstrating a novel MRI technique for the specific assessment of vasomodulation without confounding influences from changes in blood oxygen saturation, hematocrit, or flow. Methods Elevated CO2 is a safe and reliable vasodilatory stimulus and is effective in differentiating healthy from diseased vasculature. 10% CO2 was mixed with 21% oxygen and directed into an intubated rat. A blood-pool T1 contrast agent (Ablavar) was injected intravenously as a bolus (0.3mmol/kg) followed by a saline flush, to saturate the blood volume fraction, eliminating sensitivity to molecular oxygen and producing changes in T1 dominated by the blood volume fraction. The extended residency time of Ablavar, which stems from protein binding, allows a prolonged period of stable T1 signal enhancement (approx. 40 minutes). Results Exposure to 10% CO2, a known cardiac vasodilator, elicited conflicting results when compared across sexes. Young female rats demonstrated a strong vasodilatory response within 10 minutes of hypercapnic exposure, quantified through the drastic reduction in T1, while their male counterparts exhibited little to no change. When reverting to room air following 10 minutes of CO2, both male and female animals exhibited strong vasoconstriction. Young pre-diabetic female rats exhibited a blunted response when exposed to 10% CO2, losing their ability to vasodilate and constrict. Conclusion This work described a novel MRI diagnostic tool for highly specific assessment of microvascular vasomodulation and demonstrated a greater vasodilatory response to hypercapnic stimuli in healthy female rats compared to male, along with blunted response in diabetic females. This non-invasive technology will be valuable for early diagnosis of cardiac disease in patients predisposed to developing mvD.T1 myocardial microvascular reactivityBlunted pre-diabetic female stress-CMR

Oral and intravenous tranexamic acid administration demonstrate no significant difference in objective measures of blood loss in primary total shoulder arthroplasty

IntroductionThe routine use of tranexamic acid (TXA) in shoulder arthroplasty has grown in popularity due to the perceived benefits of reduction in intra-operative blood loss and the related adverse sequelae. Both intravenous (IV) and oral (PO) formulations of TXA exist and there is minimal data regarding the optimal route of administration. This study aimed to assess whether there was a significant difference in efficacy between the administration of PO vs. IV TXA prior to total shoulder arthroplasty. We hypothesized equivalence in preoperative (preop) to postoperative change in hemoglobin (Hg) and hematocrit (Hct) as well as the length of stay (LOS), 90-day readmission, transfusion rates and adverse events between the two routes. Materials and methodsA single-center retrospective chart review was conducted between May 2022 and January 2023. All patients undergoing primary anatomic or reverse total shoulder arthroplasty during this period were included. Patients undergoing revision shoulder arthroplasty or arthroplasty for fracture were excluded. The primary outcome of interest was the change (Δ) in preop to postoperative day 1 Hg and Hct reported as ΔHg and ΔHct. Intraoperative estimated blood loss (EBL), transfusion rates, patient demographics, LOS, and adverse event data were also collected. ResultsTwo hundred and thirty patients who underwent shoulder arthroplasty met the inclusion criteria. A total of 176 patients received preoppreop IV TXA and 54 patients received preop PO TXA. There was no significant difference between groups in the mean ΔHg (1.69 in the IV group and 2.52 in the PO group, P = .11) or ΔHct (5.19 in the IV group and 5.04 in the PO group, P = .42). There was no significant difference in LOS, transfusion rates, or 90-day readmission between groups. There was a significant difference in the mean EBL between the two groups (123.78cc in the IV group and 173.06cc in the PO group, P < .001). Our study was adequately powered at 0.95. ConclusionThere was no statistically significant difference between the IV and PO TXA groups when comparing preop to postoperative day 1 change in Hg and Hct, LOS, transfusion rates, surgical site infections, and 90-day readmission indicating similar efficacy between the two routes of administration. EBL was found to be significantly higher in the PO TXA group, though the clinical significance of this finding is indeterminate. Given these findings, however, PO TXA may be a reliable alternative to IV TXA in primary shoulder arthroplasty.

Abstract 11986: Erythropoietic Response After Intravenous Iron in Heart Failure With Reduced Ejection Fraction With or Without Background Treatment With Sodium-Glucose Co-Transporter 2 Inhibitors

Introduction: Intravenous (IV) iron increases hemoglobin/hematocrit and improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. Sodium glucose co-transporter 2 inhibitors (SGLT2i) also increase hemoglobin/hematocrit and improve outcomes in HF by mechanisms linked to nutrient deprivation signaling, and inflammation/oxidative stress reduction. The effect of IV iron among patients using SGLT2i has not yet been studied. Hypothesis: We hypothesize that HFrEF patients with iron deficiency treated with IV iron with a background treatment including a SGLT2i will have an increase erythropoietic response comparing to SGLT2i non users. Methods: Retrospective, single-center analysis of HFrEF patients with iron deficiency treated with IV iron using (n=60) and not using (n=60) SGLT2i, matched for age and sex. The primary outcome was the difference in absolute hemoglobin change (before vs after IV iron administration) between SGLT2i users and nonusers. The main secondary outcomes were the difference in hematocrit and iron biomarkers (total iron, ferritin and trasnferrin saturation) changes between SGLT2i users and nonusers. Results: Mean age was 73±12 years, 48% were men, with more than 65% of patients having chronic kidney disease and anemia. After adjustment for all baseline differences, SGLT2i users experienced a greater increase in hemoglobin and hematocrit compared to SGLT2i nonusers: hemoglobin +0.57 g/dL (95%CI 0.04-1.10, p=0.036) and hematocrit +1.64% (95%CI 0.18-3.11, p=0.029). No significant differences were noted for iron biomarkers or any of the secondary outcomes. Conclusion: Combined treatment with IV iron and background SGLT2i was associated with a greater increase in hemoglobin and hematocrit than IV iron without background SGLT2i. These results suggest that in HFrEF patients treated with IV iron, SGLT2i may increase the erythropoietic response.

Cerebral and intestinal oxygen saturation of different volumes of red blood cell transfusion in preterm infants

ObjectivesThe purpose of this study was to investigate and compare the effects of 20 ml/kg and 15 ml/kg red blood cell transfusion (RBCT) on cerebral and intestinal tissue oxygenation, the number of administered transfusions, and neonatal complications in premature infants with anemia. MethodsThis prospective, randomized, partially blinded observational study investigated anemic neonates of gestational age < 32 weeks (Registration ID: ChiCTR 1,900,026,672). The infants were randomly assigned to receive 15 or 20 ml/kg red blood cell transfusion. Cerebral and intestinal tissue oxygen saturation (cer rSO2 and int rSO2) were collected 2 h before transfusion, 2, 4, 6, 12, 24, and 48 h after the beginning of transfusion by Near-infrared spectroscopy (NIRS). We also collected vital signs including heart rate (HR), peripheral oxygen saturation (SpO2), and mean arterial blood pressure (MABP) 2 h before infusion, 2 h, and 6 h after the beginning of transfusion. Then we analyzed and compared regional oxygen saturation(rSO2), fractional tissue oxygen extraction (FTOE), and other outcome readouts (blood transfusion numbers, changes in hematocrit and hemoglobin, hospitalization days, HR, SpO2, MABP, and complications) between the two groups. The intraindividual comparisons of the above readouts before transfusion and those after transfusion were also evaluated within each group. Result73 newborns received 20 ml/kg (large volume group) and 78 newborns received 15 ml/kg transfusion (small volume group). There was no significant difference in cer rSO2, int rSO2, Cerebral fractional tissue oxygen extraction (cFTOE), and intestinal fractional tissue oxygen extraction (iFTOE) between the two groups. rSO2, MABP, and SpO2 increased; HR, cFTOE, and iFTOE decreased following transfusion in both groups. The transfusion number of the large volume group is significantly less than that of the small volume group (1.9 ± 0.3 vs. 2.6 ± 0.9, p < 0.01) and hospitalization days were also less than those in the low volume group (44.3 ± 8.2 vs. 47.6 ± 9.8, p < 0.05). The increases in hematocrit and hemoglobin were higher in the large volume group than those in small volume (hematocrit increment (%),10.7 ± 4.2 vs. 10.1 ± 5.9, p = 0.015; Hb concentration after blood transfusion (g/L) 132.3 ± 11.1 vs. 127.4 ± 15.4, p = 0.028). ConclusionAfter the transfusion, cer rSO2 and int rSO2 increased significantly, FTOE decreased and vital signs improved in both the 15 ml/kg and 20 ml/kg groups, and these changes were not significantly different between the two groups. However, the larger group showed a more pronounced increase in hematocrit and hemoglobin, a reduction in the total number of transfusions, and a shorter duration of hospitalization after transfusion in preterm infants without increasing complications.

Significant perioperative parameters affecting postoperative complications within 30 days following craniotomy for primary malignant brain tumors

BackgroundThe occurrence of postoperative complications within 30 days (PC1M) of a craniotomy for the removal of a primary malignant brain tumor has been associated with a poor prognosis. However, it is still unclear to early predict the occurrence of PC1M. This study aimed to identify the potential perioperative predictors of PC1M from its preoperative, intraoperative, and 24-h postoperative parameters.MethodsPatients who had undergone craniotomy for primary malignant brain tumor (World Health Organization grades III and IV) from January 2011 to December 2020 were enrolled from a databank of Kaohsiung Veterans General Hospital, Taiwan. The patients were classified into PC1M and nonPC1M groups. PC1M was defined according to the classification by Landriel et al. as any deviation from an uneventful 30-day postoperative course. In both groups, data regarding the baseline characteristics and perioperative parameters of the patients, including a new marker-kinetic estimated glomerular filtration rate, were collected. Logistic regression was used to analyze the predictability of the perioperative parameters.ResultsThe PC1M group included 41 of 95 patients. An American Society of Anesthesiologists score of > 2 (aOR, 3.17; 95% confidence interval [CI], 1.19–8.45; p = 0.021), longer anesthesia duration (aOR, 1.16; 95% CI, 0.69–0.88; p < 0.001), 24-h postoperative change in hematocrit by > − 4.8% (aOR, 3.45; 95% CI, 1.22–9.73; p = 0.0019), and 24-h postoperative change in kinetic estimated glomerular filtration rate of < 0 mL/min (aOR, 3.99; 95% CI, 1.52–10.53; p = 0.005) were identified as independent risk factors for PC1M via stepwise logistic regression analysis. When stratified according to the age of ≥ 65 years (OR, 11.55; 95% CI, 1.30–102.79; p = 0.028), the reduction of kinetic estimated glomerular filtration rate was more robustly associated with a higher risk of PC1M.ConclusionsFour parameters were demonstrated to significantly influence the risk of PC1M in patients undergoing primary malignant brain tumor removal. Measuring and verifying these markers, especially kinetic estimated glomerular filtration rate, would help early recognition of PC1M risk in clinical care.

Supine mini percutaneous nephrolithotomy in horseshoe kidney.

The percutaneous nephrolithotomy (PCNL) in Horseshoe kidneys (HSK) is usually performed in the prone position, allowing entry through the upper pole and providing good access to the collecting system. However, in patients with normal kidney anatomy, the supine position is reliable and safe in most cases, but it is unknown whether the supine position is adequate in patients with HSK. The purpose of this study was to describe the results of PCNL in HSK in three different surgical institutions and to evaluate the impact of supine position during surgery, comparing pre-operative and post-operative data, complications, and stone status after surgery. Between 2017 and 2022, a total of 10 patients underwent percutaneous renal surgery for stone disease in HSK. All patients were evaluated pre- and post- operatively with non-contrast CT. we evaluated patients (age and gender), stones characteristics (size, number, side, site and density ), and outcomes. The change in haemoglobin, hematocrit, creatinine and eGFr were assessed between the most recent preoperative period and the first postoperative day. Procedure success was defined as stone-free or presence of ≤4 mm fragments (Clinically Insignificant residual Fragments - CIrF). Complications were registered and classified according to Clavien-dindo Grading System, during the 30 - day postoperative period and Clavien scores ≥ 3 were considered as major complications. Statistical analysis was performed using "r 4.2.1" software, with a 5% significance level. we also compared pre-operative and post-operative data using "wilcoxon signedrank test". No statistical difference was observed between preoperative and post-operative renal function data. At one post operative day CT scan, an overall success rate of 100% was registered. 9/10 patients were completely free from urolithiasis (stone-free rate: 90%), while 1/10 patients had ≤4 mm residual stone fragments (CIrF rate: 10%). No cases of intraoperative complications were registered. Post-operative complications were reported in 1/10 patients. A patient developed urosepsis (defined as SIrS with clinical signs of bacterial infections involving urogenital organs - Clavien-dindo Grade II) after procedure, and was treated with intravenous antibiotic therapy successfully. Conclusions: This study shows that in patients with HSK mini- PCNL in supine position allows to achieve good stone free rate with a very low morbidity. According to our series, the described technique for PCNL in HSK should be an option. Nevertheless these results must be confirmed by further studies.

Antimalarial Activity of Nano Phytomedicine Fraction of Syzygium cumini Fruit in Rodent Malaria

The purpose of this study is to prove the antimalarial activity of nanophytomedicine fraction Syzygium cumini fruit in rodent malaria. Preparation of nanoparticle formulations using ionic gelation. This research used 80 mice divided into 8 groups. K: not infected, K-: infected, P1: infected+chloroquine, P2: infected+fraction, P3, P4, P5, were infected + nanoparticles, and P6 were infected + nanoparticles combined with chloroquine. Mice were infected with red blood cells containing 1x106 in 0.2ml P.berghei. Treatment for 4 days and 24hours post-infection. On the 8th day, post-infection blood and organs were collected. The results showed the body weight of mice showed a decrease except for the P1 and P6 groups. Increased % parasitemia and decreased parasite growth inhibition in group K- compared to P1, P6, and P5. The splenic index of the K group was significantly different from the other groups. The hepatic index of the K group was not significantly different from the P1 and P6 groups, but significantly different from the other groups. The hematological changes of hemoglobin and hematocrit in groups K- and P3 showed a decrease. Leukocytes, monocytes, and granulocytes in all groups were in the normal range. The conclusion is Nanoparticles fraction of Syzygium cumini at a dose of 400 mg/kg BW and combination therapy with chloroquine have better potential as an antimalarial seen from the decreased parasitemia, increased inhibition of parasite growth, increased body weight, splenic index, hepatic index and Hematological changes of mice infected with Plasmodium berghei.

Determining Plasma Tacrolimus Concentrations Using High-Performance LC-MS/MS in Renal Transplant Recipients.

Whole-blood therapeutic drug monitoring of tacrolimus is conducted to maintain tacrolimus concentrations within a safe and effective range. Changes in hematocrit cause variability in blood concentrations of tacrolimus because it is highly bound to erythrocytes. Measuring plasma concentrations may eliminate this variability; however, current methods have limitations owing to the use of cross-reactive immunoassays, plasma separation at nonbiological temperatures, and lack of clinical validation. This study aimed to develop and validate a clinically applicable method to measure plasma tacrolimus concentrations in renal transplant recipients and to examine the concentration differences between genotypic CYP3A5 expressors and nonexpressors. Plasma tacrolimus concentrations were measured in 9 stable renal transplant recipients who were genotypic CYP3A5 expressors or nonexpressors. Tacrolimus was extracted from plasma using solid-phase extraction, and liquid chromatography-tandem mass spectrometry was used for detection and quantitation. This assay was sensitive, selective, and linear between 100 and 5000 ng/L, with intraassay and interassay imprecision and inaccuracy <10% and <5% respectively. The extraction recovery of tacrolimus and ascomycin was 74%. Matrix ion suppression effects were 31.5% and 35% with overall recovery of 50.6% and 48.3% for tacrolimus and ascomycin, respectively. Whole-blood concentrations accounted for approximately 46% of the variation in plasma concentrations in CYP3A5 expressors and nonexpressors. No difference in dose-adjusted whole-blood and plasma concentrations was observed between CYP3A5 expressors and nonexpressors. This assay is clinically applicable with excellent performance and demonstrated that tacrolimus plasma concentrations highly correlated with whole-blood concentrations.