Improve Tissue Oxygenation Research Articles

Photosynthetic microorganisms for the oxygenation of advanced 3D bioprinted tissues.

3D bioprinting technology has emerged as a tool that promises to revolutionize the biomedical field, including tissue engineering and regeneration. Despite major technological advancements, several challenges remain to be solved before 3D bioprinted tissues could be fully translated from the bench to the bedside. As oxygen plays a key role in aerobic metabolism, which allows energy production in the mitochondria; as a consequence, the lack of tissue oxygenation is one of the main limitations of current bioprinted tissues and organs. In order to improve tissue oxygenation, recent approaches have been established for a broad range of clinical applications, with some already applied using 3D bioprinting technologies. Among them, the incorporation of photosynthetic microorganisms, such as microalgae and cyanobacteria, is a promising approach that has been recently explored to generate chimerical plant-animal tissues where, upon light exposure, oxygen can be produced and released in a localized and controlled manner. This review will briefly summarize the state-of-the-art approaches to improve tissue oxygenation, as well as studies describing the use of photosynthetic microorganisms in 3D bioprinting technologies. STATEMENT OF SIGNIFICANCE: 3D bioprinting technology has emerged as a tool for the generation of viable and functional tissues for direct in vitro and in vivo applications, including disease modeling, drug discovery and regenerative medicine. Despite the latest advancements in this field, suboptimal oxygen delivery to cells before, during and after the bioprinting process limits their viability within 3D bioprinted tissues. This review article first highlights state-of-the-art approaches used to improve oxygen delivery in bioengineered tissues to overcome this challenge. Then, it focuses on the emerging roles played by photosynthetic organisms as novel biomaterials for bioink generation. Finally, it provides considerations around current challenges and novel potential opportunities for their use in bioinks, by comparing latest published studies using algae for 3D bioprinting.

Current data regarding homeostasis of tissues oxygenation in pathophysiological and therapeutic circumstances

Abstract: Oxygen is essential for cellular respiration and energy production. Tissue oxygenation refers to delivering oxygen to cells throughout the body. Microcirculation brings blood through small sanguine vessels to maintain the cells' supply of nutrients and oxygen. Optimal tissue ox-ygenation and microcirculation are essential for maintaining healthy tissue. Conversely, poor oxygenation can cause tissue damage, impair wound healing, and increase infection risk. Several factors can affect tissue oxygenation and microcirculation, including age, lifestyle factors (such as smoking and stress), and underlying medical conditions (such as diabetes and high blood pres-sure). To improve tissue oxygenation and microcirculation, individuals can engage in healthy lifestyle habits such as regular exercise, healthy eating, stress management, and avoiding smoking. Tissue oxygenation can also be looked therapeutic, given that topical and cosmetic treatments such as massage, pelotherapy, hydrotherapy, moisturizers, and certain skin care products can help promote healthy microcirculation at the somatic level. In the scientific literature, the focus is on hypoxia rather than tissue oxygenation. This article proposes a paradigm shift and emphasizes the homeostatic importance of microcirculation and tissue oxygenation in pathophysiological and therapeutic circumstances. The systematic review of the data from the last 2 years (2021-2022) and the meta-analysis performed on tissue oxygenation will contribute to the practical approach to the pathology circumscribed to tissue oxygenation. Keywords: Tissue oxygenation; Hypoxia; Microcirculation; Homeostasis; Microenvironment

Blood Transfusion Complications and Associated Factors Among Blood-Transfused Adult Patients at Debre Markos Comprehensive Specialized Hospital, Ethiopia: A Cross Sectional Study.

Blood transfusion is the infusion of whole blood or its components into the veins of the patient to improve tissue oxygenation and maintain hemostasis. Besides its clinical use, it can pose a risk of transfusion complications with different factors. The aim of this study was to assess blood transfusion complications, and associated factors among transfused adult patients at Debre Markos Comprehensive Specialized Hospital, North West Ethiopia, 2022. An institution-based cross-sectional study design was conducted on a total of 182 patients from March 20 to June 15, 2022. Patients were enrolled in the study using consecutive sampling method. The socio-demographic and clinical data were collected using a structured questionnaire and data extraction sheet, respectively. About 3 ml of anti-coagulated blood and 30 ml of urine samples were collected to assess transfusion complications. CBC and Coombs test were performed from blood and urinalysis from urine, respectively. Chi-square, Fisher's exact test, and binary logistic regression were done using SPSS version 25. P-values less than 0.05 are declared as statistically significant. An acute transfusion reaction (ATR) was encountered in 12 (6.6%) patients. It was 4.13, 7.78 and 3.96 times more likely to occur among patients with a previous history of transfusion, abortion, and transfused blood stored for more than 20 days compared to their counterparts, respectively. In addition, the odds of developing ATR increase by 2.07 as the number of transfused blood units increases by 1 unit. The incidence of acute transfusion reactions was high. During transfusion, clinicians should closely monitor patients who had history of transfusion, abortion, transfused old blood and more than 1 unit.

Effect of hyperbaric oxygen on post-stroke depression.

In patients with post-stroke depression (PSD) in diabetes, the situation may be more complex, requiring simultaneous treatment of blood glucose, depressive symptoms, and neurological dysfunction. Hyperbaric oxygen (HBO) therapy can improve tissue oxygen content and improve the situation of ischemia and hypoxia, thus playing a role in protecting brain cells and restoring the function of brain cells. However, there are few studies on HBO therapy for patients with PSD. This study explores the clinical efficacy of such therapy for stroke complicated with depression and diabetes mellitus, and to provide reference and basis for clinical treatment and development through the application of relevant rating scales and laboratory test indicators. To evaluate the clinical effects of HBO therapy on patients with diabetes with PSD. A total of 190 diabetic patients with PSD were randomly divided into observation and control groups (95 patients per group). The control group received escitalopram oxalate 10mg once a day for eight weeks. In addition, the ob-servation group was also given HBO therapy, once a day, five times a week, for eight weeks. The Montgomery Depression Rating Scale (MADRS), National Institutes of Health Stroke Scale (NIHSS), hypersensitive C-reactive protein, tumor necrosis factor (TNF)-α, and fasting glucose levels were compared. There were no significant differences in age, sex, or depression course between the groups (P > 0.05). After HBO treatment, MADRS scores in both groups decreased significantly (14.3 ± 5.2), and were significantly lower in the control group (18.1 ± 3.5). After HBO treatment, NIHSS scores in both groups decreased significantly, and scores in the observation group (12.2 ± 4.0) decreased more than in the control group (16.1 ± 3.4), the difference was statistically significant (P < 0.001). The levels of hypersensitive C-reactive protein and TNF-α in both groups were significantly decreased, and the observation group was significantly lower than the control group (P < 0.001). Fasting blood glucose levels in both groups decreased significantly, and those in the observation group decreased more (8.02 ± 1.10) than in the control group (9.26 ± 1.04), with statistical significance (t = -7.994, P < 0.001). HBO therapy can significantly improve depressive symptoms and neurological dysfunction in patients with PSD, and reduce the levels of hypersensitive C-reactive protein, TNF-α and fasting blood glucose.

Muscle oxygen utilization and ventilatory parameters during exercise in people with cystic fibrosis: Role of HbA1c.

Glycated hemoglobin can interfere with oxygen delivery and CO2 removal during exercise. Additionally, pancreatic insufficiency increases oxidative stress and exacerbates exercise intolerance in people with cystic fibrosis (PwCF). This investigation sought to test the hypotheses that elevated Hemoglobin A1c (HbA1c) can negatively affect exercise parameters in PwCF and that reductions in oxidative stress can improve tissue oxygenation in individuals with elevated HbA1c. Twenty four PwCF were divided into two groups; normal HbA1c <5.7% (N-HbA1c) and elevated HbA1c >5.7% (E-HbA1c). A maximal exercise test was conducted to obtain peak oxygen uptake (VO2peak), VO2 at ventilatory threshold (VT), ventilatory parameters (VE/VCO2 slope and end-tidal CO2 (petCO2)). Near-Infrared Spectroscopy (NIRS) was used to assess muscle oxygenated/deoxygenated hemoglobin during exercise. A subset of individuals with E-HbA1cwere given an antioxidant cocktail (AOC) for 4weeks to determine the effects on tissue oxygenation during exercise. A negative relationship between HbA1c and VO2peak at VT was observed (r = -0.511; p = 0.018). In addition, a positive relationship between HbA1c and VE/VCO2 slope (r = 0.587;p = 0.005) and a negative relationship between HbA1c and petCO2 at maximal exercise (r = -0.472;p = 0.031) was observed. N-HbA1c had greater VO2peak (p = 0.021), VO2 at VT (p = 0.004), petCO2 (p = 0.002), and lower VE/VCO2 slope (p = 0.004) compared with E-HbA1c. Muscle deoxygenated hemoglobin at VT was higher in N-HbA1c vs. E-HbA1c and 4weeks of AOC improved skeletal muscle utilization of oxygen. Findings demonstrate that glycated hemoglobin may lead to tissue oxygenation impairment and ventilation inefficiency during exercise in PwCF. In addition, antioxidant supplementation may lead to improved tissue oxygenation during exercise.

Hyperosmolar therapy for regulation of cerebral edema and intracranial pressure

Background: Hyperosmolar therapy is an essential treatment method for increased intracranial pressure and cerebral edema. Mannitol and hypertonic saline are frequently used in clinical practice; however, more helpful recommendations are needed for the optimal management of cerebral edema in terms of the choice, dosage, and timing of these medications. This study aimed to introduce the characteristics and relative strengths of two agents, i.e., mannitol and hypertonic saline, and review clinical data supporting their use in various diseases.Current Concepts: Hyperosmolar therapy reduces intracranial pressure by removing water from the brain tissue and transferring it to the vascular space by creating an osmotic gradient. Mannitol improves cerebral blood flow by reducing the hematocrit, decreasing blood viscosity, and increasing deformability of red blood cells. Hypertonic saline increases intravascular volume, transiently increases cardiac output, and improves tissue oxygen partial pressure in the brain. Hypertonic saline has several advantages over mannitol, including quicker onset and longer-lasting reduction in intracranial pressure. However, no significant differences are noted in clinical, functional outcomes, or mortality between the two treatment agents.Discussion and Conclusion: Both mannitol and hypertonic saline are effective in reducing increased intracranial pressure. Clinicians should be able to select an appropriate agent in different clinical situations based on available evidence and patients’ individual medical conditions.

Haemodynamic changes during prone versus supine position in patients with COVID-19 acute respiratory distress syndrome

BackgroundProne positioning improves oxygenation in patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19. However, its haemodynamic effects are poorly understood. ObjectivesThe objective of this study was to investigate the acute haemodynamic changes associated with prone position in mechanically ventilated patients with COVID-19 ARDS. The primary objective was to describe changes in cardiac index with prone position. The secondary objectives were to describe changes in mean arterial pressure, FiO2, PaO2/FiO2 ratio, and oxygen delivery (DO2) with prone position. MethodsWe performed this cohort-embedded study in an Australian intensive care unit, between September and November 2021. We included adult patients with severe COVID-19 ARDS, requiring mechanical ventilation and prone positioning for respiratory failure. We placed patients in the prone position for 16 h per session. Using pulse contour technology, we collected haemodynamic data every 5 min for 2 h in the supine position and for 2 h in the prone position consecutively. ResultsWe studied 18 patients. Cardiac index, stroke volume index, and mean arterial pressure increased significantly in the prone position compared to supine position. The mean cardiac index was higher in the prone group than in the supine group by 0.44 L/min/m2 (95% confidence interval, 0.24 to 0.63) (P < 0.001). FiO2 requirement decreased significantly in the prone position (P < 0.001), with a significant increase in PaO2/FiO2 ratio (P < 0.001). DO2 also increased significantly in the prone position, from a median DO2 of 597 mls O2/min (interquartile range, 504 to 931) in the supine position to 743 mls O2/min (interquartile range, 604 to 1075) in the prone position (P < 0.001). ConclusionProne position increased the cardiac index, mean arterial pressure, and DO2 in invasively ventilated patients with COVID-19 ARDS. These changes may contribute to improved tissue oxygenation and improved outcomes observed in trials of prone positioning.

Control of tissue oxygenation by S-nitrosohemoglobin in human subjects

S-Nitrosohemoglobin (SNO-Hb) is unique among vasodilators in coupling blood flow to tissue oxygen requirements, thus fulfilling an essential function of the microcirculation. However, this essential physiology has not been tested clinically. Reactive hyperemia following limb ischemia/occlusion is a standard clinical test of microcirculatory function, which has been ascribed to endothelial nitric oxide (NO). However, endothelial NO does not control blood flow governing tissue oxygenation, presenting a major quandary. Here we show in mice and humans that reactive hyperemic responses (i.e., reoxygenation rates following brief ischemia/occlusion) are in fact dependent on SNO-Hb. First, mice deficient in SNO-Hb (i.e., carrying C93A mutant Hb refractory to S-nitrosylation) showed blunted muscle reoxygenation rates and persistent limb ischemia during reactive hyperemia testing. Second, in a diverse group of humans-including healthy subjects and patients with various microcirculatory disorders-strong correlations were found between limb reoxygenation rates following occlusion and both arterial SNO-Hb levels (n = 25; P= 0.042) and SNO-Hb/total HbNO ratios (n = 25; P= 0.009). Secondary analyses showed that patients with peripheral artery disease had significantly reduced SNO-Hb levels and blunted limb reoxygenation rates compared with healthy controls (n = 8 to 11/group; P< 0.05). Low SNO-Hb levels were also observed in sickle cell disease, where occlusive hyperemic testing was deemed contraindicated. Altogether, our findings provide both genetic and clinical support for the role of red blood cells in a standard test of microvascular function. Our results also suggest that SNO-Hb is a biomarker and mediator of blood flow governing tissue oxygenation. Thus, increases in SNO-Hb may improve tissue oxygenation in patients with microcirculatory disorders.

Hyperbaric oxygenation therapy improve recovery in early or late vascular occlusion generates by tissue fillers.

Aesthetic medicine is characterized by the efficacy and safety of treatments. Although sometimes adverse events could be occurred, in this case vascular occlusion is the most serious of them. The tissue is deprived of oxygen and there is a possibility of necrosis, so it is necessary to remove the tissue filler and promote oxygenation. We propose the hyperbaric oxygenation treatment to oxygenate the tissue after vascular occlusion generated by a tissue filler such as Hyaluronic Acid. We show how hyperbaric oxygenation treatment is an adjuvant therapy after vascular occlusion, improving tissue regeneration and prevent or limit scars or sequelae. Hyperbaric oxygenation treatment isa safeandeffective method to treat vascular accident, improving tissue oxygenation in early cases and improving tissue regeneration in cases with necrosis.

BIOMICROSCOPY HIGHLIGHTS THE EFFICACY OF SKIN GRAFT ON MICROVASCULAR PARAMETERS IN NON-DIABETIC ULCERS

Objective. Laser Doppler owmetry (LDF), transcutaneous partial pressure of oxygen (pO2) and carbon dioxide (pCO2), and Biomicroscopy (BM) are exams used in daily clinical practice to assess capillary and microvascular functionality. Skin graft (SG) is a well-established intervention for the treatment of chronic lower leg ulcers. The sequence of improvements at the microvascular and macrovascular level, letting to a successful outcome after SG, is not yet been determined. This observation aims to determine which parameters of capillary functionality could show how SG takes to a positive outcome. Methods. In this trial, cutaneous perfusion, district microcirculatory reserve, and variation of cutaneous perfusion induced by the postural vasoconstriction reex (VAR) were measured with LDF as the number and diameter of capillary loops at 1 cm, 2 cm, and 4 cm from the big toe nailfold and the ulcer edge. Cutaneous gas exchanges were detected through pO2 and pCO2, and capillary density and average diameter loops were recorded with BM. Because of the exploratory nature of this study, consecutive patients' afferent to our structure receiving SG for the treatment of non-diabetic chronic non-relapsing ulcers on the lower limb, were assessed before and 5 days after SG. All measures were collected by the same operator and SG was performed in a standardized manner. Paired non-parametric statistical tests were performed to compare basal with after SG measurements. Results. All 13 patients observed had a clinically successful outcome after SG in terms of pain reduction, absence of SG complications, and absence of secretion. The median number of capillary loops changed at the different evaluation points (e.g. from 19 vs 21 (P=.004) at the big toe nailfold and 16 vs. 22 (P&lt;.001) at 2 cm from the ulcer edge). The median diameter of capillary loops changed at the different evaluation points (e.g. at the big toe nailfold decreased from 24mm to 19mm (P=.004) and from 16mm to 22mm (P=.031) at 2 cm from the ulcer). The median values of pO2 increased from 10 mmHg to 36 mmHg (P=.005) on supine and from 28 mmHg to 3 mmHg (P=.006) at the dependent lower limb None of the LDF measures, or pCO2.Conclusion.In this exploratory evaluation, BM measurements reveal, for the rst time, a successful outcome after SG for the treatment of chronic lower limb skin ulcers, especially on the big toe nailfold, 1 and 2 cm from the ulcer. The improvement observed at the capillary level seems parallel with the improvement of tissue oxygenation

Hypoxia signaling in cancer: Implications for therapeutic interventions.

Hypoxia is a persistent physiological feature of many different solid tumors and a key driver of malignancy, and in recent years, it has been recognized as an important target for cancer therapy. Hypoxia occurs in the majority of solid tumors due to a poor vascular oxygen supply that is not sufficient to meet the needs of rapidly proliferating cancer cells. A hypoxic tumor microenvironment (TME) can reduce the effectiveness of other tumor therapies, such as radiotherapy, chemotherapy, and immunotherapy. In this review, we discuss the critical role of hypoxia in tumor development, including tumor metabolism, tumor immunity, and tumor angiogenesis. The treatment methods for hypoxic TME are summarized, including hypoxia-targeted therapy and improving oxygenation by alleviating tumor hypoxia itself. Hyperoxia therapy can be used to improve tissue oxygen partial pressure and relieve tumor hypoxia. We focus on the underlying mechanisms of hyperoxia and their impact on current cancer therapies and discuss the prospects of hyperoxia therapy in cancer treatment.

The Efficacy of Erythrocyte Transfusion in Very Low Birth Weight Infants with Premature Anemia

Objective: This study aimed to determine the clinical efficacy of erythrocyte transfusion (ET) in premature infants. Material and Methods: Very low birth weight (VLBW) infants with gestational age (GA) &amp;lt; 32 weeks and/or birth weight (BW) &amp;lt;1500 g and hospitalized in neonatal intensive care unit (NICU) between 2012-2018 were retrospectively evaluated. ET was performed according to Ohls 2007 and Turkish Neonatalogy Society Blood Products Transfusion Guidelines. Results: 72 infants included in this study. Mean BW was 1325 g (680-2290 g), GA was 30 weeks (25-32), median postnatal age was 36.7±26.9 days (8-129), number of ET during hospitalization was 2±1.2 (1-6). There were no significant changes in mean heart rates (p=0.183) and median respiratory rates before and after ET (p=0.123). Weight gain (16 g/day-11 g/day) was statistically similar before and after ET (p=0.861). A significant decrease in apnea, non-invasive ventilation (NIV) and caffeine therapy requirements after ET was determined (p&amp;lt;0.001, p=0.016 and p=0.016). Serum lactate (2.9-1.5) levels were decreased by ET (p=0.017). Conclusion: Premature infants should closely follow-up for anemia and related symptoms during NICU stay. ET may help to decrease frequency of apnea of prematurity, requirements of caffeine therapy and NIV. ET improves tissue oxygenation in VLBW infants with anemia. Decision of ET should be made according to severity of symptoms, and should be performed according to international, national or local transfusion guidelines.

Cardiac Rehabilitation and Cardiopulmonary Fitness in Children and Young Adults With Congenital Heart Diseases: A Critically Appraised Topic.

Public health guidelines and a myriad of studies have proven that exercise is beneficial in the alleviation of various cardio-metabolic diseases. Congenital heart disease (ConHD) is one of the most frequently occurring congenital structural malfunctions in the pediatric population, affecting nine of every 1,000 live births. Only a few studies have established the impact of a structured exercise program on cardiopulmonary fitness in diverse groups of patients with ConHD. It is also alarming to know that a substantial number of these patients and their caregivers often remain very wary of exercise. Anxiety about exercise may increase the risk of developing morbid obesity and other long-term health complications of ConHD. The present review of a critically appraised topicis undertaken to answer the question, "Does structured exercise intervention (cardiac rehabilitation) improve cardiorespiratory fitness in children and young adults with ConHD?" Exercise science and the medical literature were searched for studies that engaged the use of aerobic exercise in patients with different ConHD diagnoses. The search yielded four studies after screening with the inclusion and exclusion criteria, which were further narrowed to three studies after a full-text review. These studies yielded results showing significant increments in peak exercise workload, duration, power output, peak oxygen uptake, or improved tissue oxygenation and muscle strength after an exercise training intervention. It is noteworthy that a group identified as "cyanotic palliated" exhibited the most significant impairment both at baseline and after the exercise intervention. This review provides level 1b medical evidence that a structured exercise program may improve cardiopulmonary fitness in patients with ConHD, which is likely to be beneficial to their overall physical, motor, and psychosocial development. The results of this review may be useful for alleviating the anxiety of patients and their caregivers about participation in structured exercise programs. This review should also motivate future research investigations to develop clinical guidelines for the management of patients with ConHD by adding exercise prescriptions to their daily therapeutic regimens.

Increasing oxygen tension in tumor tissue using ultrasound sensitive O2 microbubbles.

Low tissue oxygenation significantly impairs the effectiveness of cancer therapy and promotes a more aggressive phenotype. Many strategies to improve tissue oxygenation have been proposed throughout the years, but only a few showed significant effects in clinical settings. We investigated stability and ultrasound pulse (UP) triggered oxygen release from phospholipid coated oxygen microbubbles (OMB) in vitro and in murine tumors in vivo using EPR oximetry. In solution, the investigated microbubbles are stable and responsive to ultrasound pulse. The addition of the OMB solution alone resulted in an increase in pO2 of approximately 70mmHg which was further increased for an additional 80mmHg after the application of UP. The in vivo kinetic study revealed a substantial, up to 120mmHg, increase in tumor pO2 after UP application and then pO2 was decreasing for 20min for intravenous injection and 15min for intratumoral injection. A significant increase was also observed in groups that received microbubbles filled with nitrogen and ultrasound pulse and OMB without UP, but the effect was much lower. Oxygen microbubbles lead to a decrease in HIF-1a and VEGF-A both at the level of mRNA and protein. Toxicity analysis showed that intravenous injection of OMB does not cause oxidative damage to the heart, liver, or kidneys. However, elevated levels of oxidative damage to lipids and proteins were observed short-term in tumor tissue. In conclusion, we have demonstrated the feasibility of oxygen microbubbles in delivering oxygen effectively and safely to the tumor in living animals. Such treatment might enhance the effectiveness of other anticancer therapies.

Comparison of Waterlogging Tolerance of Three Peach Rootstock Seedlings Based on Physiological, Anatomical and Ultra-Structural Changes

Peach (Prunus persica (L.) Batsch) is a typical shallow-rooted fruit plant with a high respiratory intensity and oxygen demand, which makes it highly susceptible to oxygen-deficient soil conditions resulting from waterlogging. Rootstock waterlogging resistance is essential to the performance of cultivated peaches under waterlogging stress. In comparison to Prunus persica var. persica (‘Maotao’, M) and Prunus davidiana (Carr.) C. de Vos (‘Shantao’, S), Prunus persica f. Hossu (‘Hossu’, H) exhibited superior leaf photosynthetic electron transfer efficiency, a higher rate of mycorrhizal fungi infection in both fine roots and mesophyll palisade cells, as well as earlier air cavity formation in both leaf midvein and fine roots under waterlogging stress. Furthermore, under non-waterlogging conditions, Hossu had greater leaf superoxide dismutase (SOD) activity, higher proline content, and a greater content of starch granules in the pith and xylem ray cells of stems and roots than rootstocks M and S. As a result, Hossu’s tolerance to waterlogging may be due to its higher photosynthetic efficiency, improved tissue oxygen permeability, higher energy metabolism, and increased intracellular mycorrhizal fungus infection rates in both root parenchyma cells and mesophyll palisade cells.

The pleiotropic effects of α-thalassemia on HbSS and HbSC sickle cell disease: Reduced erythrocyte cation co-transport activity, serum erythropoietin, and transfusion burden, do not translate into increased survival.

α‐Thalassemia is one of the most important genetic modulators of sickle cell disease (SCD). Both beneficial and detrimental effects have been described previously. We use a 12‐year data set on a large cohort of patients with HbSS (n = 411) and HbSC (n = 146) to examine a wide range of these clinical and laboratory associations. Our novel findings are that α‐thalassemia strongly reduces erythrocyte potassium chloride co‐transporter (KCC) activity in both HbSS and HbSC (p = .035 and p = .00045 respectively), suggesting a novel mechanism through which α‐thalassemia induces a milder phenotype by reducing red cell cation loss. This may be particularly important in HbSC where reduction in mean cell hemoglobin concentration is not seen and where KCC activity has previously been found to correlate with disease severity. Additionally, we show that α‐thalassemia not only increases hemoglobin in patients with HbSS (p = .0009) but also reduces erythropoietin values (p = .0005), demonstrating a measurable response to improved tissue oxygenation. We confirm the reno‐protective effect of α‐thalassemia in patients with HbSS, with reduced proteinuria (p = .003) and demonstrate a novel association with increased serum sodium (p = .0004) and reduced serum potassium values (p = 5.74 × 10−10). We found patients with α‐thalassemia had a reduced annualized transfusion burden in both HbSS and HbSC, but α‐thalassemia had no impact on annualized admission rates in either group. Finally, in a larger cohort, we report a median survival of 62 years in patients with HbSS (n = 899) and 80 years in those with HbSC (n = 240). α‐thalassemia did not influence survival in HbSS, but a nonsignificant trend was seen in those with HbSC.

Intraoperative haemodynamic optimisation using the Hypotension Prediction Index and its impact on tissular perfusion: a protocol for a randomised controlled trial

IntroductionIntraoperative arterial hypotension is associated with poor postoperative outcomes. The Hypotension Prediction Index (HPI) developed using machine learning techniques, allows the prediction of arterial hypotension analysing the arterial pressure waveform....

Effects of ischemic conditioning on head and neck free flap oxygenation: a randomized controlled trial

Flap failure after microvascular reconstructive surgery is a rare but devastating complication caused by reperfusion injury and tissue hypoperfusion. Remote ischemic conditioning (RIC) provides protection against ischemia/reperfusion injury and reduces tissue infarction. We hypothesized that RIC would enhance flap oxygenation and exert organ-protective effects during head and neck free flap reconstructive surgery. Adult patients undergoing free flap transfer surgery for head and neck cancer were randomized to receive either RIC or sham-RIC during surgery. RIC consisted of four cycles of 5-min ischemia and 5-min reperfusion applied to the upper or lower extremity. The primary endpoint, tissue oxygen saturation of the flap, was measured by near-infrared spectroscopy on the first postoperative day. Organ-protective effects of RIC were evaluated with infarct size of rat hearts perfused with plasma dialysate from patients received RIC or sham-RIC. Between April 2018 and July 2019, 50 patients were randomized (each n = 25) and 46 were analyzed in the RIC (n = 23) or sham-RIC (n = 23) groups. Tissue oxygen saturation of the flap was similar between the groups (85 ± 12% vs 83 ± 9% in the RIC vs sham-RIC groups; P = 0.471). Myocardial infarct size after treatment of plasma dialysate was significantly reduced in the RIC group (44 ± 7% to 26 ± 6%; P = 0.018) compared to the sham-RIC group (42 ± 6% to 37 ± 7%; P = 0.388). RIC did not improve tissue oxygenation of the transferred free flap in head and neck cancer reconstructive surgery. However, there was evidence of organ-protective effects of RIC in experimental models.Trial registration: Registry number of ClinicalTrials.gov: NCT03474952.

Optimizing transfusion therapy for survivors of Haemoglobin Bart's hydrops fetalis syndrome: Defining the targets for haemoglobin-H fraction and "functional" haemoglobin level.

Owing to the unique pathophysiology of anaemia in haemoglobin Bart's hydrops fetalis (HBHF), a transfusion strategy based on beta-thalassemia guidelines is suboptimal for chronically transfused HBHF patients. A more aggressive transfusion aimed at reducing the proportion of non-functional HbH and improving the "functional" haemoglobin (f-Hb) can lead to reduced haemolysis and improved tissue oxygenation. However, the optimal transfusion targets for these parameters are not yet defined. In this retrospective, longitudinal study on four chronically transfused patients with HBHF, we used receiver operating characteristic curves to find a pre-transfusion f-Hb of 106g/l and a HbH of 16.1% to be the optimal thresholds to achieve a normal soluble transferrin receptor and lactate dehydrogenase, respectively.

Blood Group Testing.

Red blood cell (RBC) transfusion is one of the most frequently performed clinical procedures and therapies to improve tissue oxygen delivery in hospitalized patients worldwide. Generally, the cross-match is the mandatory test in place to meet the clinical needs of RBC transfusion by examining donor-recipient compatibility with antigens and antibodies of blood groups. Blood groups are usually an individual's combination of antigens on the surface of RBCs, typically of the ABO blood group system and the RH blood group system. Accurate and reliable blood group typing is critical before blood transfusion. Serological testing is the routine method for blood group typing based on hemagglutination reactions with RBC antigens against specific antibodies. Nevertheless, emerging technologies for blood group testing may be alternative and supplemental approaches when serological methods cannot determine blood groups. Moreover, some new technologies, such as the evolving applications of blood group genotyping, can precisely identify variant antigens for clinical significance. Therefore, this review mainly presents a clinical overview and perspective of emerging technologies in blood group testing based on the literature. Collectively, this may highlight the most promising strategies and promote blood group typing development to ensure blood transfusion safety.