Calcium flux alterations in erythrocytes from sickle cell mice: The relevance of mean corpuscular volume.

Red blood cells (RBC) from patients with sickle cell disease (SCD) have elevated calcium levels at baseline, which are further elevated upon deoxygenation. Here we examined baseline calcium levels and calcium flux in RBCs from a mouse model of SCD mice. We found that akin to humans with SCD, sickle (HbSS) Townes mice, have higher baseline levels and increased calcium flux in RBCs compared to control (HbAA) animals. As HbSS mice, unlike humans with SCD, have high mean corpuscular volume compared with HbAA, we highlight the importance of adjusting biochemical results to number of RBCs rather than hematocrit during the analysis and interpretation of the results. Our findings add to the face validity of humanized sickle cell mice and support its use for studies of RBC calcium flux in SCD.

Rises in Hematocrit Are Associated With an Increased Risk of Major Adverse Cardiovascular Events in Men Starting Testosterone Therapy: A Retrospective Cohort Claims Database Analysis.

PURPOSE: Elevated hematocrit (Hct) can result in increased risk of major adverse cardiovascular events (MACE) in men receiving testosterone therapy (TTh). However, the impact of the magnitude of the change in Hct from baseline after starting TTh has never been assessed. MATERIALS AND METHODS: To assess whether an increase in Hct after initiating TTh is associated with an increased risk of MACE within 3 and 24 months of initiating TTh, we queried the TriNetX Research network database for men over the age of 18 with Hct values obtained within 6 months before starting TTh, and who had follow-up Hct measurements within 3 and 24 months after beginning TTh from 2010 to 2021. Men with and without a subsequent increase in Hct after initiating TTh were propensity matched. MACE was defined as myocardial infarction, stroke, or death. RESULTS: After matching, 10,511 men who experienced an any increase in Hct after initiating TTh and an equal number of controls who did have an increase in Hct were included. Compared to controls who did not have an increase in Hct after starting TTh, the men who had an increase in subsequent Hct had a significantly increased risk of MACE compared to men with no change in Hct. CONCLUSIONS: We demonstrate that increases in Hct from baseline are associated with increased risk of MACE, compared to men whose Hct remains stable while receiving TTh.

Study of the f-cell ratio using plasma dilution and albumin mass kinetics.

BACKGROUND: The f-cell ratio of 0.91 is a conversion factor between the hematocrit measured in peripheral blood and the hematocrit obtained by separate measurements of the red blood cell mass and plasma volume. The physiological background of the f-cell ratio is unclear. METHODS: Data were retrieved from 155 intravenous infusion experiments where 15-25 mL/kg of crystalloid fluid diluted the blood hemoglobin and plasma albumin concentrations. The hemodilution was converted to plasma dilution using the peripheral hematocrit, and the volume of distribution of exogenous albumin was calculated in 41 volunteers who received 20 % or 5 % albumin by intravenous infusion. Finally, the kinetics of plasma albumin was studied during 98 infusion experiments with 20 % albumin. RESULTS: Plasma dilution based on hemoglobin and albumin showed a median difference of -0.001 and a mean difference of 0.000 (N = 2184), which demonstrates that these biomarkers indicate the same expandable vascular space. In contrast, exogenous albumin occupied a volume that was 10 % larger than the plasma volume indicated by the anthropometric equations of Nadler et al. and Retzlaff et al. The kinetic analysis identified a secondary compartment that was 450 mL in size and rapidly exchanged albumin with the circulating plasma. CONCLUSIONS: The results suggest that the f-cell ratio is due to rapid exchange of albumin between the plasma and a non-expandable compartment located outside the circulating blood (possibly the liver sinusoids). This means that the hematocrit measured in peripheral blood correctly represents the ratio between the red cell volume and the circulating plasma volume.

Association between Hematocrit and Acute Kidney Injury in Patients with Acute Myocardial Infarction.

Backgrounds: Hematocrit is found an independent risk factor for acute kidney injury (AKI) in certain patients, but this effect in patients with acute myocardial infarction (AMI) is unclear. We aim to identify the relationship between hematocrit and AKI in patients with AMI. Methods: The patient data for the discovery and validation cohorts were extracted from the electronic Intensive Care Unit database and the Medical Information Mart for Intensive Care III database, respectively, to identify the relationship between hematocrit and AKI. With normal hematocrit as the reference, patients were divided into five groups based on the initial hematocrit value. The primary outcome was AKI during hospitalization. A multivariable logistic regression and a marginal effect analysis were used to evaluate the relationship between hematocrit and AKI. Results: In this study, a total of 9692 patients diagnosed with AMI were included, with 7712 patients in the discovery cohort and 1980 patients in the validation cohort. In the discovery cohort, hematocrit in 30-33%, 27-30% or < 27% were independent risk factors for AKI in the multivariate logistic analysis, with odds ratio (OR) of 1.774 (95% confidence interval [CI]: 1.203-2.617, p = 0.004), 1.834 (95% CI: 1.136-2.961, p = 0.013) and 2.577 (95% CI: 1.510-4.397, p < 0.001), respectively. Additionally, in the validation cohort, low hematocrit levels independently contributed to an increased risk of AKI among patients with AMI. During the analysis of marginal effects, a significant negative linear relationship between hematocrit levels and AKI was observed. Conclusions: Decreased hematocrit was an independent risk factor for AKI in patients with AMI. The relationship between hematocrit and AKI was negative linear.

Impact of systematic variations in hematocrit and platelet count on thrombelastometry tissue factor activated assay parameters.

BACKGROUND: Thromboelastogram testing is increasingly being used to manage patients with massive bleeding. An earlier study found that the test results were influenced by the hematocrit (Hct) and platelet (PLT) concentrations. This study sought to determine if these factors confounded the results of a different manufacturer's thromboelastography testing. METHODS: Using freshly collected whole blood from volunteers and stored red blood cells (RBC) and plasma, the whole blood was manipulated to achieve different Hct values and PLT concentrations. Each reconstituted whole blood sample was tested in triplicate on the ROTEM Delta device and the ExTEM results were recorded. RESULTS: Many of the ExTEM results varied according to the Hct and PLT concentration. In particular, the ExTEM clot formation time (CFT) was abnormally long when the Hct was 45% and the PLT concentration was ≤75 × 109/L, normalizing only when the PLT count was ≥100 × 109/L. CFT samples with Hct 25% and 35% were also abnormal with low PLT concentrations but normalized at lower PLT concentrations compared to the Hct 45% samples. The ExTEM angle also demonstrated abnormal results when the Hct was 45% and the PLT concentration was ≤50 × 109/L. The ExTEM A10 and maximum clot firmness (MCF) tests tended to also be abnormal when the Hct was between 25% and 45% and the platelet concentrations were below 75 × 109/L. CONCLUSION: While thromboelastogram testing is gaining popularity for managing bleeding patients, clinicians should be aware of these confounding factors when making transfusion decisions based on their results.

Hematocrit control and thrombotic risk in patients with polycythemia vera treated with ruxolitinib in clinical practice.

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by unregulated red blood cell production resulting in elevated hemoglobin and/or hematocrit levels. Patients often have symptoms such as fatigue, pruritus, and painful splenomegaly, but are also at risk of thrombosis, both venous and arterial. Ruxolitinib, a selective Janus kinase inhibitor, is approved by the US Food and Drug Administration as second-line cytoreductive treatment after intolerance or inadequate response to hydroxyurea. Although ruxolitinib has been widely used in this setting, limited data exist in the literature on ruxolitinib treatment patterns and outcomes among patients with PV in routine clinical practice. We report a retrospective, observational, cohort study of patients treated for PV with ruxolitinib across three US centers (academic and regional practice) from December 2014-December 2019. The study included 69 patients, with a median follow-up duration of 3.7 years (95% CI, 2.9-4.4). Our data demonstrate very high rates of hematocrit control (88% of patients by three months and 89% by six months); few patients required dose adjustments or suspension. No arterial thromboses were observed; however, the follow-up duration does not allow for the generation of meaningful conclusions from this. Three patients had thrombotic events; one was in the setting of a second malignancy, one post-operative, and a third related to prolonged immobility. We also found that 28% of patients initiated ruxolitinib as a result of poorly controlled platelet counts, second only to hydroxyurea intolerance (46%) as a reason to start therapy. In clinical practice, ruxolitinib continues to be effective in controlling hematocrit levels after three and six months of treatment in patients and is associated with low thrombotic risk.

Ruxolitinib in patients with polycythemia vera resistant and/or intolerant to hydroxyurea: European observational study.

BACKGROUND: Hydroxyurea (HU) is a commonly used first-line treatment in patients with polycythemia vera (PV). However, approximately 15%-24% of PV patients report intolerance and resistance to HU. METHODS: This phase IV, European, real-world, observational study assessed the efficacy and safety of ruxolitinib in PV patients who were resistant and/or intolerant to HU, with a 24-month follow-up. The primary objective was to describe the profile and disease burden of PV patients. RESULTS: In the 350 enrolled patients, 70% were >60 years old. Most patients (59.4%) had received ≥1 phlebotomy in the 12 months prior to the first dose of ruxolitinib. Overall, 68.2% of patients achieved hematocrit control with 92.3% patients having hematocrit <45% and 35.4% achieved hematologic remission at month 24. 85.1% of patients had no phlebotomies during the study. Treatment-related adverse events were reported in 54.3% of patients and the most common event was anemia (22.6%). Of the 10 reported deaths, two were suspected to be study drug-related. CONCLUSION: This study demonstrates that ruxolitinib treatment in PV maintains durable hematocrit control with a decrease in the number of phlebotomies in the majority of patients and was generally well tolerated.

Impact of etiology, sex, diabetes mellitus and remission status on erythrocytic profile in patients with cushing's syndrome: a large population database study.

PURPOSE: The study aimed to characterize the erythrocytic profile in patients with cushing's syndrome (CS) versus controls from the normal population according to etiology, sex, presence of diabetes mellitus (DM) and hypercortisolemia remission status. METHODS: This retrospective cohort analysis compared erythrocytic parameters between patients with CS of pituitary (CD) and adrenal (aCS) etiology and age, sex, body mass index (BMI) and socioeconomic status-matched controls in a 1:5 ratio. Laboratory values at baseline were calculated as mean values during the year preceding CS diagnosis, and over one year thereafter. RESULTS: The cohort included 397 CS patients (68.26% female; mean age 51.11 ± 16.85 years) and 1970 controls. Patients with CS had significantly higher baseline median levels of hemoglobin (Hgb) (13.70 g/dL vs. 13.12 g/dL [p < 0.0001]) and hematocrit (Hct) (41.64% vs. 39.80% [p < 0.0001]) compared to controls. These differences were observed for both CD and aCS and for both sexes. Patients who attained remission had Hgb and Hct levels comparable to controls (13.20 g/dL and 40.08% in patients with CD and aCS vs. 13.20 g/dL and 39.98% in controls). Meanwhile, those with persistent/recurrent disease maintained elevated levels. Patients with comorbid DM had similar Hgb but higher Hct (p = 0.0419), while patients without DM showed elevated erythrocytic values compared to controls (p < 0.0001). CONCLUSION: Our data illustrates that erythrocytic parameters are directly influenced by glucocorticoid excess as Hgb and Hct are higher in patients with CS, and normalize after remission. We have identified the influence of DM on erythrocytic parameters in patients with CS for the first time.

Increased risk of erythrocytosis in men with type 2 diabetes treated with combined sodium-glucose cotransporter-2 inhibitor and testosterone replacement therapy.

PURPOSE: In clinical trials, sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and testosterone replacement therapy (TRT) were shown to stimulate red blood cell production. Little is known if combination therapy poses risk of erythrocytosis in real world clinical practice. METHODS: This was a retrospective nationwide cohort study of US Veterans with type 2 diabetes (T2D) and baseline hematocrit between 38 and 50% who were prescribed SGLT-2i and/or TRT between 3/2013 and 10/2022 and had adequate adherence based on the proportion of days covered > 80%. Patients were divided into 3 groups: SGLT-2i only, TRT only, or combination therapy. Odds Ratio (OR) of new erythrocytosis defined as hematocrit level > 54% within 365 days of therapy initiation was calculated by logistic regression model adjusted for baseline hematocrit, age, BMI, obstructive sleep apnea, diuretic use, and smoking status. RESULTS: Of the entire cohort of 53,971 people with T2D, total of 756 (1.4%) patients developed erythrocytosis. In unadjusted analyses, the OR of new onset erythrocytosis was higher in the combined SGLT-2i and TRT group compared with the SGLT-2i or TRT group alone (4.99, 95% CI (3.10-7.71) and 2.91, 95% CI (1.87-4.31), respectively). In the models adjusted for baseline characteristics, patients on combination therapy had significantly higher odds of erythrocytosis compared to those on SGLT-2i (OR 3.80, 95% CI (2.27-6.11)) or TRT alone (OR 2.49, 95% CI (1.51-3.59)). Testosterone delivery route (topical vs injectable) did not modify increased odds of erythrocytosis. CONCLUSIONS: For the first time, we demonstrated that in large cohort of patients combined therapy with SGLT-2i and TRT is associated with increased erythrocytosis risk compared with either treatment alone. Given rising prevalence of SGLT-2i use, providers should consider periodic hematocrit assessment in persons receiving both SGLT-2i and TRT.

Prediction of hematocrit decline and the impact of peri-operative fluid use in lumbar spinal fusion surgery.

PURPOSE: Peri-operative blood loss unaccounted for and post-operative hematocrit decline could have a significant impact on the outcome of elective spinal surgery patients. The study assesses the accuracy of predictive models of hematocrit decline and blood loss in spinal surgery and determines the impact of peri-operative fluid administration on hematocrit levels of patients undergoing first-time single level lumbar fusion surgery for degenerative spine disease and the trend thereof in the first 24 h post-operatively. METHODS: Clinical and biochemical parameters were prospectively collected in patients undergoing single level lumbar spinal surgery. Predictive models were applied to assess their accuracy in intra-operative blood loss and post-operative hematocrit decline. RESULTS: High correlation (0.98 Pearson correlation coefficient) occurred between calculated (predicted) and recorded hematocrit from hours 2 to 6 post-operatively. Predictive accuracy declined thereafter yet remained moderate. Patients received an average intra-operative fluid volume of 545.45 ml per hour (47% of estimated total blood volume). A significant hematocrit decline occurred post-induction (43.47-39.78%, p < 0.001) with total fluid volume received being the significant contributing variable (p < 0.001). Hypertensive patients were the only subgroup to drop below the safe hematocrit threshold of 30%. CONCLUSION: Iatrogenic hemodilution can accurately be predicted for the first six hours post-operatively, with high risk patients identifiable. Fluid therapy should be goal directed rather than generic, and good communication between the surgeon and anesthesiologist remains the cornerstone to manage physiological changes secondary to blood loss. Although helpful, predictive formulas are not universally applicable to all phenotypes.

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

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

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.

Hematocrit drift and outcomes in surgical patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: There is a paucity of conclusive evidence regarding the impact of downward drift in hematocrit levels among patients who have undergone surgical clipping for aneurysmal subarachnoid hemorrhage (aSAH). This study endeavors to explore the potential association between hematocrit drift and mortality in this specific patient population. METHODS: A cohort study was conducted, encompassing adult patients diagnosed with aSAH at a university hospital. The primary endpoint was follow-up mortality. Propensity score matching was employed to align patients based on their baseline characteristics. Discrimination capacity across various models was assessed and compared using net reclassification improvement (NRI). RESULTS: Among the 671 patients with aSAH in the study period, 118 patients (17.6%) experienced an in-hospital hematocrit drift of more than 25%. Following adjustment with multivariate regression analysis, patients with elevated hematocrit drift demonstrated significantly increased odds of mortality (aOR: 2.12, 95% CI: 1.14 to 3.97; P = 0.019). Matching analysis yielded similar results (aOR: 2.07, 95% CI: 1.05 to 4.10; P = 0.036). The inclusion of hematocrit drift significantly improved the NRI (P < 0.0001) for mortality prediction. When in-hospital hematocrit drift was served as a continuous variable, each 10% increase in hematocrit drift corresponded to an adjusted odds ratio of 1.31 (95% CI 1.08-1.61; P = 0.008) for mortality. CONCLUSIONS: In conclusion, the findings from this comprehensive cohort study indicate that a downward hematocrit drift exceeding 25% independently predicts mortality in surgical patients with aSAH. These findings underscore the significance of monitoring hematocrit and managing anemia in this patient population.

Evaluation of Blood Loss in Third-Generation Internal Ultrasound-Assisted Liposuction.

BACKGROUND: In large-volume liposuction procedures, one of the most important limitations of total lipoaspirate volume is blood loss. In this study, we aimed to determine the amount of blood loss in individuals who underwent a third-generation internal ultrasound-assisted liposuction (UAL). METHODS: Eleven female and eleven male participants with a mean age of 35.31 (range 20-47) were included in this prospective study. The third-generation internal UAL was performed on multiple anatomical regions using the VASER® Internal Ultrasound Device (Sound Surgical Technologies; Louisville, CO). The demographic characteristics of the participants, the amount of aspirate collected, and hemoglobin (Hgb) and hematocrit (Htc) values before and after the third-generation internal UAL were evaluated. RESULTS: The mean third-generation internal UAL time was 74.81 ± 17.95 minutes, and the mean aspiration amount was 5,122.27 ± 1,597.43 ml. The aspirated amount was 6.64% ± 2.20 of body weight. The mean Hgb value was 13.87 ± 1.99 before the third-generation internal UAL and 11.26 ± 2.16 (g/dL) after the third-generation internal UAL (z = 4.108, p < 0.001). The mean reduction in Hgb levels with the third-generation internal UAL was 2.61 ± 1.73 and 0.53 ± 0.36 per liter of aspirate taken. The mean Htc value after the third-generation internal UAL was 33.91 ± 6.03 and was significantly lower than the mean Htc value before the third-generation internal UAL, 41.39 ± 5.13 (z = -3.946, p < 0.001). The mean reduction in Htc with the third-generation internal UAL was 7.48 ± 5.42, and the Htc value decreased by 1.50 ± 1.13 per liter of aspirate ingested. The amount of aspirated supernatant was responsible for 44.4% of the change in Hgb and 30.9% of the change in Htc after the third-generation internal UAL. CONCLUSION: Knowing the reduction rates in Hgb and Htc with the third-generation internal UAL is useful to plan the amount of aspirate to be taken, the amount of blood loss that may occur with the third-generation internal UAL, and the postoperative care of the patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Acute effects of apnea bouts on hemoglobin concentration and hematocrit: a systematic review and meta-analysis.

Objective: This study aimed to systematically analyze the existing literature and conduct a meta-analysis on the acute effects of apnea on the hematological response by assessing changes in hemoglobin (Hb) concentration and hematocrit (Hct) values. Methods: Searches in Pubmed, The Cochrane Library, and Web of Science were carried out for studies in which the main intervention was voluntary hypoventilation, and Hb and Hct values were measured. Risk of bias and quality assessments were performed. Results: Nine studies with data from 160 participants were included, involving both subjects experienced in breath-hold sports and physically active subjects unrelated to breath-holding activities. The GRADE scale showed a "high" confidence for Hb concentration, with a mean absolute effect of 0.57 g/dL over control interventions. "Moderate" confidence appeared for Hct, where the mean absolute effect was 2.45% higher over control interventions. Hb concentration increased to a greater extent in the apnea group compared to the control group (MD = 0.57 g/dL [95% CI 0.28, 0.86], Z = 3.81, p = 0.0001) as occurred with Hct (MD = 2.45% [95% CI 0.98, 3.93], Z = 3.26, p = 0.001). Conclusions: Apnea bouts lead to a significant increase in the concentration of Hb and Hct with a high and moderate quality of evidence, respectively. Further trials on apnea and its application to different settings are needed.

Efficacy of essential oil from ginger (Zingiber officinale) for anesthesia and transport sedation of pacu (Piaractus mesopotamicus).

This study evaluated the anesthetic and sedative effects of the essential oil of Zingiber officinale (EOZO) on juvenile pacu (Piaractus mesopotamicus). Experiment 1 evaluated concentrations of 0, 50, 100, 200 and 400 mg L-1 EOZO for times of induction and recovery from anesthesia. Furthermore, hematological responses and residual components of EOZO in plasma were determined immediately after anesthesia. Experiment 2 evaluated the effect of 0, 10, 20 and 30 mg L-1 EOZO on water quality, blood variables and residual components of EOZO in plasma and tissues (muscle and liver) immediately after 2 h of transport. Survival was 100%. The three main compounds of EOZO [zingiberene (32.27%), ß-sesquiphellandrene (18.42%) and ß-bisabolene (13.93%)] were observed in animal plasma and tissues (muscle and liver) after anesthesia and transport, demonstrating a direct linear effect among the evaluated concentrations. The concentration of 200 mg L-1 EOZO promoted surgical anesthesia of pacu and prevented an increase in monocyte and neutrophil levels, yet did not alter other hematological parameters. The use of 30 mg L-1 EOZO has a sedative effect on juvenile pacu, thereby reducing oxygen consumption during transport. Furthermore, the use of 30 mg L-1 EOZO in transport water prevented an increase in hemoglobin and hematocrit, with minimal influences on other blood variables.

Comparison of Hematocrit Change in Testosterone-deficient Men Treated With Intranasal Testosterone Gel vs Intramuscular Testosterone Cypionate: A Randomized Clinical Trial.

PURPOSE: Our primary aim was to compare changes in hematocrit in testosterone-deficient men treated with intranasal testosterone gel vs intramuscular testosterone cypionate. MATERIALS AND METHODS: This 2-arm, open-label, randomized trial recruited men with testosterone deficiency at the University of Miami between August 2020 and October 2022. Men with 2 total testosterone levels <350 ng/dL and hypogonadal symptoms, aged 18-75 years were randomly assigned to receive either intranasal testosterone gel 11 mg 3 times daily or intramuscular testosterone cypionate 200 mg every 2 weeks. The primary outcome was change in hematocrit after 4 months of treatment. Secondary outcomes were changes in serum testosterone, estradiol, prostate-specific antigen, 17-hydroxyprogesterone, and the 6-item International Index of Erectile Function. RESULTS: Of the 81 men randomized, 54 completed treatment (intranasal n=23; intramuscular n=31). The mean age was 47.5 vs 49.5 years, with mean baseline testosterone of 244.6 vs 240.7 ng/dL and mean hematocrit of 44.4% vs 42.7% in intranasal vs intramuscular groups, respectively. Men who received intramuscular injections had a significant increase after 4 months of treatment in mean hematocrit from 42.7% to 46.6% (P < .0001), but there was no significant change in men who received intranasal gel (P = .233). Men in both groups experienced significantly increased serum testosterone levels throughout the study period, though a larger increase was seen in men treated with intramuscular injections (mean change 511 vs 283, P = .025). Men who received injections also experienced an increase in estradiol (mean change 22.9, P < .001), decrease in 17-hydroxyprogesterone (mean change -39.8, P < .0001), and increase in the 6-item International Index of Erectile Function score (mean change 4.8, P = .015); men treated with intranasal gel experienced no such changes. Prostate-specific antigen levels were stable in both groups. CONCLUSIONS: Intranasal testosterone gel does not appear to significantly affect hematocrit levels. Men who wish to avoid polycythemia or changes in estradiol or 17-hydroxyprogesterone levels may benefit from short-acting testosterone therapy formulations such as intranasal gel.

Real-world treatments and thrombotic events in polycythemia vera patients in the USA.

Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased risk of thrombotic events (TE) and death. Therapeutic interventions, phlebotomy and cytoreductive medications, are targeted to maintain hematocrit levels < 45% to prevent adverse outcomes. This retrospective observational study examined medical and pharmacy claims of 28,306 PV patients initiating treatment for PV in a data period inclusive of 2011 to 2019. Study inclusion required ≥ 2 PV diagnosis codes in the full data period, at least 1 year of PV treatment history, and ≥ 1 prescription claim and medical claim in both 2018 and 2019. Patients having ≥ 2 hematocrit (HCT) test results in linked outpatient laboratory data (2018-2019) were designated as the HCT subgroup (N = 4246). Patients were characterized as high- or low-risk at treatment initiation based on age and prior thrombotic history. The majority of patients in both risk groups (60% of high-risk and 83% of low-risk) initiated treatment with phlebotomy monotherapy, and during a median follow-up period of 808 days, the vast majority (81% low-risk, 74% high-risk) maintained their original therapy during the follow-up period. Hematocrit control was suboptimal in both risk groups; 54% of high-risk patients initiating with phlebotomy monotherapy sometimes/always had HCT levels > 50%; among low-risk patients, 64% sometimes/always had HCT levels above 50%. Overall, 16% of individuals experienced at least 1 TE subsequent to treatment initiation, 20% (n = 3920) among high-risk and 8% (n = 629) among low-risk patients. This real-world study suggests that currently available PV treatments may not be used to full advantage.

Hydration and evaporative water loss of lizards change in response to temperature and humidity acclimation.

Testing acclimation plasticity informs our understanding of organismal physiology and applies to conservation management amidst our rapidly changing climate. Although there is a wealth of research on the plasticity of thermal and hydric physiology in response to temperature acclimation, there is a comparative gap for research on acclimation to different hydric regimes, as well as the interaction between water and temperature. We sought to fill this gap by acclimating western fence lizards (Sceloporus occidentalis) to experimental climate conditions (crossed design of hot or cool, dry or humid) for 8 days, and measuring cutaneous evaporative water loss (CEWL), plasma osmolality, hematocrit and body mass before and after acclimation. CEWL changed plastically in response to the different climates, with lizards acclimated to hot humid conditions experiencing the greatest increase in CEWL. Change in CEWL among individuals was negatively related to treatment vapor pressure deficit and positively related to treatment water vapor pressure. Plasma osmolality, hematocrit and body mass all showed greater changes in response to temperature than to humidity or vapor pressure deficit. CEWL and plasma osmolality were positively related across treatment groups before acclimation and within treatment groups after acclimation, but the two variables showed different responses to acclimation, suggesting that they are interrelated but governed by different mechanisms. This study is among few that assess more than one metric of hydric physiology and that test the interactive effects of temperature and humidity. Such measurements will be essential for predictive models of activity and survival for animals under climate change.

A theoretical model for the Fåhræus effect in medium-large microvessels.

This paper presents a mathematical model capable to reproduce a celebrated phenomenon in blood microcirculation known as Fåhræus effect, since its discovery by Robin Fåhræus (1929). This consists in a decaying of the relative hematocrit in small vessels as the vessel diameter decreases. The key point of the model is a formula, direct consequence of the basic principles of fluid dynamics, that links the relative hematocrit to the reservoir hematocrit and the vessel diameter, which confirms the observed behavior. To test the model we selected, among the few experiments carried on since then, those performed by Barbee and Cokelet (1971). The agreement is remarkable. An extended comparison is also carried out with a celebrated empirical formula proposed by Pries et al. (1992) to describe the same phenomenon.