Blood Draw Research Articles

297. ASSESSING BLOOD-BASED BIOMARKERS IN OESOPHAGEAL CANCER PATIENTS RECEIVING NEOADJUVANT CHEMORADIOTHERAPY

Abstract Background Oesophageal cancer is the sixth most common cause of cancer-related deaths globally. It has a significant rate of mortality despite the multimodal approach to treatment. Neo-adjuvant chemoradiotherapy is standard of care but there is a clinical need for new therapies. HER2-targeted therapies and immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have emerged as treatment strategies of significant interest in recent years. This study focuses on exploring potential plasma-based biomarkers (growth factors, cytokines, soluble (s) PD-L1) in patients (pts) with oesophageal cancer receiving standard of care neo-adjuvant therapy and stratified based on HER2 expression and pathological complete response (pCR). Methods 50 pts with oesophageal cancer who are eligible for neoadjuvant therapy were recruited. Blood samples were taken pre-treatment, on the first day of the 2nd cycle and post-neoadjuvant treatment. Plasma was extracted within four hours of blood draw and stored at -800C. 20 matched pre- and post-treatment samples were included in this analysis. HER2 status (IHC 3+ (n=3), IHC 2+ (n=5), IHC 1+ (n=3), IHC 0 (n=6) was available for 17 pts. 3 pts achieved a pCR but no HER2 IHC data was available. The levels (pg/ml) of 21 analytes were assessed using the Human Growth Factor Luminex Performance Assay and a Luminex MagPix system. Changes were significant if p<0.05, paired student’s t test. Results Twenty-one biomarkers of response were assessed in the final analysis. Platelet-derived growth factor (PDGF)-AA and PDGF AA/BB displayed the highest concentration levels of the tested analytes but levels did not change pre-and post-treatment. GRO-b (CXCL2) and vascular endothelial growth factor (VEGF) displayed a numerical increase post-treatment but this did not prove significant (p<0.05). Tumour-necrosis factor-related apoptosis-inducing ligand (TRAIL) protein decreased significantly post-therapy (p=0.038). PD-L1 levels significantly increased in the post-treatment cycles (paired t-test p=0.0029), especially in pts with HER2+ status. TRAIL or sPD-L1 levels were not significantly different when categorised by HER2 IHC or pCR status. Conclusion The increase in sPD-L1 and reduction in TRAIL levels in the peripheral blood of oesophageal cancer patients following neoadjuvant therapy suggests treatment alters factors associated with immune-suppression and the induction of tumour cell death. Further investigation in a larger cohort is warranted.

Pulse Wave Velocity as a Tool for Cardiometabolic Risk Stratification in Individuals With Hypertensive Disorders of Pregnancy and Increased BMI

ObjectivesObesity is one of the most prevalent risk factors for hypertensive disorders of pregnancy (HDP); however, the role of pre-pregnancy cardiometabolic health in the development of these conditions is not well understood. Carotid-femoral pulse wave velocity (PWV) is an established measure of arterial stiffness and cardiovascular health and is validated in pregnancy. Our objective was to examine the obesity-related changes in PWV in pregnant individuals with and without HDP. MethodsOverall, 87 individuals with singleton pregnancies were recruited and classified into 2 groups: cases (HDP: including pre-existing/chronic hypertension, gestational hypertension, preeclampsia, or intrauterine growth restriction; n = 39) and normotensive controls (no HDP or intrauterine growth restriction; n = 48). Patient data, including BMI, were collected from patient charts. Measurements of PWV were performed weekly until discharge or delivery (gestational age 24–37 weeks) and placental growth factor (PlGF) was measured at routine blood draws. ResultsPWV did not significantly change over gestation for either group. Cases had significantly increased PWV and decreased PlGF compared to normotensive controls. An elevated BMI was associated with higher PWV in both cases and controls. Once grouped based on BMI, PWV was only significantly higher in cases with a BMI ≥25 kg/m2 compared to controls, whereas PlGF was less affected by BMI. As PWV increased, PlGF decreased; however, after controlling for BMI, there was no relationship between PWV and PlGF. ConclusionsPWV measurements in early pregnancy may be useful as an additional independent marker to PlGF for risk-stratifying for HDP, especially in individuals with increased BMI.

Cord blood utilization as a blood conservation measure in the neonatal intensive care unit

Extremely low birth weight (ELBW) and very low birth weight (VLBW) infants are often exposed to several laboratory blood draws throughout their neonatal intensive care unit (NICU) stay, particularly at admission. Required routine admission labs place patients at risk for iatrogenic blood loss and need for treatment. Studies have demonstrated that blood collected from an umbilical cord segment may be used to obtain admission labs rather than drawing blood directly from the patient. The purpose of the quality improvement (QI) project was to determine if the utilization of umbilical cord blood for routine admission labs compared to the standard practice of infant phlebotamization result in fewer cases of iatrogenic anemia and the need for treatment in ELBW and VLBW infants. The following outcomes were monitored pre/post-implementation: number of blood transfusions, intra-ventricular hemorrhage (IVH) diagnosis, IVH severity, and vasopressor use. Despite a small sample size, statistically significant results were obtained.

Platelet-Rich Plasma (PRP) Based on Simple and Efficient Integrated Preparation Precises Quantitatively for Skin Wound Repair.

Platelet-rich plasma (PRP) has become an important regenerative therapy. However, the preparation method of PRP has not been standardized, and the optimal platelet concentration for PRP used in skin wound repair is unclear, leading to inconsistent clinical efficacy of PRP. Therefore, the development of standardized preparation methods for PRP and the investigation of the dose-response relationship between PRP with different platelet concentrations and tissue regeneration plays an important role in the development and clinical application of PRP technology. This study has developed an integrated blood collection device from blood drawing to centrifugation. Response surface methodology was employed to optimize the preparation conditions, ultimately achieving a platelet recovery rate as high as 95.74% for PRP (with optimal parameters: centrifugation force 1730× g, centrifugation time 10 min, and serum separation gel dosage 1.4 g). Both in vitro and in vivo experimental results indicate that PRP with a (2×) enrichment ratio is the most effective in promoting fibroblast proliferation and skin wound healing, with a cell proliferation rate of over 150% and a wound healing rate of 78% on day 7.

Waning Humoral Immune Response Following the Third and Fourth SARS-COV-2 Vaccine: A Cohort Study in Healthcare Workers.

This study is aimed at providing information about the timing of booster doses and antibody kinetics in healthcare workers. This research extends a prospective cohort study conducted at Dokuz Eylul University Hospital in Turkey, covering the period from March 2021 to December 2021. During this timeframe, the antibody levels of the health workers were measured at four different time points. The associations of antibody levels with gender, age, occupation, body mass index (BMI), chronic disease, and smoking were analyzed. There was a significant difference between antibody levels in all four blood draws (p < 0.001). Antibody levels decreased in both those vaccinated with BNT162b2 (p < 0.001) and those vaccinated with CoronaVac (p = 0.002) until the fourth blood draw. There was a significant difference between those vaccinated with one and two doses of booster BNT162b2 before the third blood draw (p < 0.001), which continued at the fourth blood draw (p < 0.001). The antibody levels of those with an interval of 41-50 days between two vaccinations decreased significantly at the fourth blood draw (p < 0.001). This study provides insight into the dynamics and persistence of antibody response after additional COVID-19 vaccine doses among healthcare workers. The longer the interval between booster doses may result in greater antibody levels being maintained over time, allowing for longer durations of protection.

Blood Donation Service to The Sidanegara Cilacap Community

The scarcity of blood is assumed to be caused by a lack of public knowledge about blood donation. Donor health advantages can minimize the danger of cancer, help with weight loss, make the body psychologically better and prolong life, reduce the risk of heart and blood vessel disease, and detect major disorders. Aside from carrying out the Tri Dharma of Higher Education, community service activities seek to encourage local residents to donate blood for the safety of others, hence raising people's desire and willingness to contribute. PMI Cilacap supports this program by sending numerous medical personnel to perform blood draws. The service team distributed information about the benefits of blood donation during this activity. There were 62 registered blood donors, with 43 (69.35%) passing the health check and donating blood, and 19 (30.65%) failing (not passing) the health check and so unable to donate blood.

Characterization of circulating tumor cells in patients with metastatic bladder cancer utilizing functionalized microfluidics

Assessing the molecular profiles of bladder cancer (BC) from patients with locally advanced or metastatic disease provides valuable insights, such as identification of invasive markers, to guide personalized treatment. Currently, most molecular profiling of BC is based on highly invasive biopsy or transurethral tumor resection. Liquid biopsy takes advantage of less-invasive procedures to longitudinally profile disease. Circulating tumor cells (CTCs) isolated from blood are one of the key analytes of liquid biopsy. In this study, we developed a protein and mRNA co-analysis workflow for BC CTCs utilizing the graphene oxide (GO) microfluidic chip. The GO chip was conjugated with antibodies against both EpCAM and EGFR to isolate CTCs from 1 mL of blood drawn from BC patients. Following CTC capture, protein and mRNA were analyzed using immunofluorescent staining and ion-torrent-based whole transcriptome sequencing, respectively. Elevated CTC counts were significantly associated with patient disease status at the time of blood draw. We found a count greater than 2.5 CTCs per mL was associated with shorter overall survival. The invasive markers EGFR, HER2, CD31, and ADAM15 were detected in CTC subpopulations. Whole transcriptome sequencing showed distinct RNA expression profiles from patients with or without tumor burden at the time of blood draw. In patients with advanced metastatic disease, we found significant upregulation of metastasis-related and chemotherapy-resistant genes. This methodology demonstrates the capability of GO chip-based assays to identify tumor-related RNA signatures, highlighting the prognostic potential of CTCs in metastatic BC patients.

Blood metal concentrations and cardiac structure and function in total joint arthroplasty patients.

There is concern regarding potential long-term cardiotoxicity with systemic distribution of metals in total joint arthroplasty (TJA) patients. To determine the association of commonly used implant metals with echocardiographic measures in TJA patients. The study comprised 110 TJA patients who had a recent history of high chromium, cobalt or titanium concentrations. Patients underwent two-dimensional, three-dimensional, Doppler and speckle-strain transthoracic echocardiography and a blood draw to measure metal concentrations. Age and sex-adjusted linear and logistic regression models were used to examine the association of metal concentrations (exposure) with echocardiographic measures (outcome). Higher cobalt concentrations were associated with increased left ventricular end-diastolic volume (estimate 5.09; 95%CI: 0.02-10.17) as well as left atrial and right ventricular dilation, particularly in men but no changes in cardiac function. Higher titanium concentrations were associated with a reduction in left ventricle global longitudinal strain (estimate 0.38; 95%CI: 0.70 to 0.06) and cardiac index (estimate 0.08; 95%CI, -0.15 to -0.01). Elevated cobalt and titanium concentrations may be associated with structural and functional cardiac changes in some patients. Longitudinal studies are warranted to better understand the systemic effects of metals in TJA patients.

A pilot pragmatic randomized controlled trial of a nicotine metabolite ratio-guided smoking cessation intervention in a lung health and screening program

IntroductionPatients with pulmonary nodules detected through lung cancer screening or as incidental findings are often followed in lung health and screening programs. The use of personalized pharmacotherapy for smoking cessation informed by the nicotine metabolite ratio (NMR), a measure of nicotine metabolism, has not yet been evaluated in this setting. This pilot randomized controlled trial (RCT) evaluated the feasibility of conducting a larger trial. MethodsThrough a pragmatic RCT design, participants were recruited from a Mid-Atlantic lung health and screening program. Eligible participants smoked >5 cigarettes per day and completed a blood draw to determine NMR before being randomized to standard or NMR-guided care treatment arms. Standard care participants were offered nicotine replacement therapy (NRT) or varenicline and a referral to phone-based smoking cessation counseling. NMR-guided participants received standard care except they were provided a personalized medication recommendation based on their NMR. Study outcomes included measures of feasibility, medication uptake, and treatment matching (i.e., uptake of the optimal medication). ResultsMore than 80 % of 205 screened patients were eligible. However, only 37 (22 %) of these patients enrolled in the study, with a mean age of 65 years, 43 % female, and 25 % Black. Nearly all patients who declined cited a disinterest in smoking cessation. Participants in both treatment arms had high rates of medication uptake (68 %), with NMR-guided participants showing a trend towards greater treatment matching (55 % vs. 29 %). ConclusionsThe results of this pilot study provide support for conducting a larger RCT of an NMR-guided smoking cessation intervention in a lung health and screening setting. Consideration should be given to augmenting the intervention to address barriers to study entry.

Overcoming Barriers to Latino Participation in Alzheimer's Disease Research.

There is a critical need to increase Latino participation in research on Alzheimer's disease and related disorders (ADRD). Applying principles of community-based participatory research, we convened a community advisory board (CAB) to identify barriers and recommend strategies to increase participation of older Latinos in a longitudinal observational research study of ADRD at the Shiley-Marcos Alzheimer's Disease Research Center. Six major barriers were identified and programmatic changes to overcome them were implemented. Changes resulted in a nearly three-fold increase in the number of Latino individuals recruited, with the proportion of all newly recruited participants who were Latino increasing from 12.2% to 57.4%. Newer Latino recruits were more representative of the elderly Latino population in San Diego County than those recruited pre-CAB and remained highly agreeable to blood draw and neuroimaging, though less so to lumbar puncture and autopsy. Results demonstrate the value of CAB involvement in enhancing diversity in ADRD research.

Recruitment and retention of pediatric participants for pandemic preparedness research: Experience from the PREMISE EV-D68 Pilot Study

Recruitment and retention are challenges for prospective pediatric cohort studies, particularly those involving serial venipunctures. We investigated factors underlying enrollment and retention in the Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) Enterovirus D68 (EV-D68) Pilot Study, a multicenter prospective longitudinal cohort study assessing the utility of immunologic surveillance for pandemic preparedness. This study enrolls children ≤10 years for two blood draws, pre- and post-EV-D68 season, separated by 6–18 months. Overall, 174 children were enrolled in Cohort 1 of the study and 120 (69 %) of children completed the study, with follow-up blood samples obtained from 101 (58 %) of participants. Families were primarily motivated to participate by a desire to help other children, advance science, and better prepare for the next pandemic. Adding research blood draws to clinically indicated blood draws improved enrollment, and multiple study touch points facilitated retention. These findings can be applied to improve recruitment and retention in future pandemic preparedness efforts and longitudinal pediatric cohort studies.

The independent and combined effects of aerobic exercise intensity and dose differentially increase post-exercise cerebral shear stress and blood flow.

This research examined the impact of aerobic exercise intensity and dose on acute post-exercise cerebral shear stress and blood flow. Fourteen young adults (27±5years of age, eight females) completed a maximal oxygen uptake ( ) treadmill test followed by three randomized study visits: treadmill exercise at 30% of for 30min, 70% of for 30min and 70% of for a duration that resulted in caloric expenditure equal to that in the 30% visit (EqEE). A venous blood draw and internal carotid artery (ICA) ultrasound were collected before and immediately following exercise. ICA diameter and blood velocity were determined using automated edge detection software, and blood flow was calculated. Using measures of blood viscosity, shear stress was calculated. Aerobic exercise increased ICA shear stress (time: P=0.005, condition: P=0.012) and the increase was greater following exercise at 70% (∆4.1±3.5dyn/cm2) compared with 30% (∆1.1±1.9dyn/cm2; P=0.041). ICA blood flow remained elevated following exercise (time: P=0.002, condition: P=0.010) with greater increases after 70% (Δ268±150mL/min) compared with 30% (∆125±149mL/min; P=0.041) or 70% EqEE (∆127±177mL/min; P=0.004). Therefore, aerobic exercise resulted in both intensity- and dose-dependent effects on acute post-exercise ICA blood flow whereby vigorous intensity exercise provoked a larger increase in ICA blood flow compared to light intensity exercise when performed at a higher dose.

CORRECT-MRD I: A clinical validation study to predict recurrence in stage II-III colorectal cancer (CRC) using a bespoke circulating tumor DNA (ctDNA) assay to detect molecular residual disease (MRD).

TPS98 Background: Despite standard of care management with surgery ± adjuvant chemotherapy treatment (ACT), &gt;30% of patients (pts) with resectable CRC recur. The presence of ctDNA in plasma after resection and after ACT, has been shown to be a strong prognostic factor for the risk of recurrence, suggesting that the presence of ctDNA in blood is molecular evidence of residual disease. As such, ctDNA analysis may enable post-surgical risk stratification for ACT decision-making, as well as detection of molecular recurrence during surveillance and subsequent early intervention. The CORRECT-I study aims to validate the association of post-definitive therapy and pre-recurrence follow-up ctDNA positivity with recurrence-free interval (RFI) in pts who have undergone complete surgical resection for stage II or III CRC. Methods: This study is a prospective, observational, multicenter study, which is open in Israel, Italy, Japan, Spain, and the UK. Pts must have pathologically confirmed stage II or III CRC, have undergone complete surgical resection, and have tissue available from the primary resection. Pts may not have started ACT prior to baseline blood draw post-surgery. Pts are asked to provide serial whole blood specimens for ctDNA analysis at a) post-surgical baseline, b) pre-recurrence follow-up visits (max 15 blood draws over max 5 years), and c) clinical recurrence. ctDNA will be analyzed with an NGS-based tumor-informed MRD assay that identifies somatic genomic alterations from DNA derived from the patient’s tumor tissue and detects a selected subset of tumor-specific (bespoke) ctDNA in their blood. The primary objective of this study is to validate the association of post-definitive therapy and serial pre-recurrence follow-up ctDNA positivity with RFI, using a Cox proportional hazards regression analysis. Further objectives include the assessment of sensitivity and specificity of the ctDNA assay, the association between ctDNA at individual timepoints and RFI, ctDNA dynamics and RFI, and the time from ctDNA positivity to clinical recurrence. A multivariable model, including ctDNA, clinicopathological risk features, serial serum CEA assessments, and recurrence risk as determined by the Oncotype Colon Recurrence Score will be fit with RFI as endpoint. The primary analysis will be conducted when ≥30 histologic and/or radiographic confirmed cases of clinical recurrence have been observed. As of April 2, 2024, 158 pts of 400 have been enrolled.

A novel cell-free multi-omics approach for enhancing multi-cancer early detection.

103 Background: While circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection (MCED) have shown significant potential, their performance is hindered by the limited amount and inherent variability of ctDNA, particularly in cancer types with low ctDNA shedding. To enhance the accuracy of MCED, recent studies have focused on profiling cell-free RNA (cfRNA), which is secreted not only by tumor cells but also by other cell types to reflect the systemic tumor responses. Herein, we developed a novel cell-free multi-omics approach integrating cfDNA and cfRNA analyses from a single blood draw to improve the sensitivity of an MCED assay, especially for detecting low-shedding ctDNA cancer types. Methods: We recruited 535 healthy subjects and 287 patients across five cancer types (77 breast cancers, 102 colorectal cancers, 35 gastric cancers, 34 liver cancers, and 42 lung cancers). We established a multi-omics workflow to comprehensively profile cfDNA signatures (methylation, fragment length, motif ends, and copy number alterations), and cfRNA signatures (cfmRNA). Distinctive signatures were identified to differentiate cancers from healthy subjects and used for constructing robust machine learning classifiers. Results: We identified multiple significantly different features distinguishing cancer from healthy individuals, with 81% originating from cfDNA. Notably, cfmRNA features, accounting for 19% of total significant features, were mainly enriched in immune-related pathways, reflecting tumor-immune cell interactions. The cfDNA-based model achieved 81.2% accuracy, with highest performance in detecting liver cancer (100%) and 64%, 42%, and 36.4% for breast, colorectal, and gastric cancers, respectively, at 93% specificity. Combining cfDNA and cfRNA signatures increased sensitivity to 73%, 71%, and 46% for breast, colorectal, and gastric cancers. Overall, the multi-omic model achieved 85.6% accuracy and 72.7% sensitivity for detecting five cancer types at 92.6% specificity. Conclusions: The cell-free multi-omics approach holds potential for improving ctDNA-based MCED tests by simultaneously profiling both cfDNA and transcriptomic cfmRNA from a single blood draw. Validation on larger cohorts could lead to a paradigm shift in cancer screening practices.

Flexible Graphene-Based Sensors for Electrochemical Analysis of Human Saliva and Sweat

Flexible carbon nanomaterial sensors offer a low-cost, facile fabrication approach toward producing sensors at an industrial scale for electrochemical sensing. Graphene and carbon nanotube (CNT) based sensors have been studied, with various fabrication methods available, including producing high-quality thin film graphene and CNTs via chemical vapor deposition (CVD). However, CVD is a high-temperature vacuum process that is low-yielding and consequently costly, hindering its implementation into single-use test strip sensors. Other methods, such as inkjet or aerosol printing, are more cost-effective as they print graphene inks obtained from liquid-phase exfoliation of graphite, which can be performed using large batch processing techniques. Additionally, the laser-induced graphene (LIG) technique directly converts sp3 carbon found in carbon-rich substrates, such as polyimide, into conductive sp2-hybridized carbon found in graphene through a laser scribing technique. Saliva and sweat offer promising biological fluids for precision health monitoring and diagnostics due to the non-invasive nature of their sampling (no need for a blood draw at a laboratory or a fingerstick at home) and due to the abundance of medically relevant analytes. Saliva can also be used for monitoring infections such as COVID-19 infection. Herein, we introduce graphene-based flexible sensors fabricated using scalable manufacturing based on aerosol jet printing (AJP) using custom-formulated graphene inks and laser-induced graphene via direct writing. We report a label-free, high-sensitivity, and rapid-response-time graphene-based electrochemical immunosensor for quantitatively detecting the SARS-CoV-2 Spike Receptor-Binding Domain (RBD) as well as SARS-CoV-2 Spike S1 protein. We demonstrate LIG-based electrochemical sensors for real-time monitoring of glucose, lactate, and sodium in sweat, and potassium and lactate in saliva. Different electrochemical methods are used, including amperometric, potentiometric, coulometric, and impedimetric, to quantify the analytes. All these electrochemical sensors were validated in human saliva and sweat and demonstrated to have limits of detection and linear sensing ranges that are relevant to their sensing applications. Flexibility studies were also performed to evaluate the ability of the sensors to operate under stresses caused by bending, such as those that would be encountered by skin and implanted oral sensors. Results demonstrate the utility of AJP-graphene and LIG for rapid and sensitive measurement of biological analytes and pathogen infection as simple methods for scalable production of non-invasive salivary and perspiration (sweat) health sensors.

The Impact of Kaleidoscope and Distraction Cards on Pain Level During Blood Drawing in Children

Aim: This study is designed as a randomized controlled experimental study to investigate the impact of kaleidoscope and distraction cards on the pain level of child patients during blood drawing procedure. Method: The population of the study was composed of children between the ages of 7-12 years who came to the pediatric blood drawing department of Alanya Training and Research Hospital between August 01, 2022 and November 15, 2022. The study sample included a total of ‘57’ children who met the criteria of the study, who came to the pediatric blood drawing department, who volunteered to take part in the study, and who were randomly selected from among the children between the ages of 7 and 12 years old with the consent of their parents as 28 study (separate kaleidoscope group and attention diversion cards were administered) and 19 control (no kaleidoscope or attention diversion card was administered) groups. The data were obtained by using the “Descriptive Information Form”, “Visual Equivalence Scale (VAS)”, and “Wong Baker Rating Scale for Facial Expressions”. During blood drawing from the children in the study group, kaleidoscope and distraction cards were used. In the control group, standard blood drawing procedure was used without any intervention. Moreover, mean, percentage, chi-square, t-test, t-test in dependent and independent groups were used to analyze the data. Results: It was found that the use of distraction cards and kaleidoscope significantly reduced the level of pain (p

Cardiovascular and hematological responses to a dry dynamic apnea in breath hold divers.

The mammalian dive reflex, characterized by bradycardia and peripheral vasoconstriction, occurs in all mammals, including humans, in response to apnea. However, the dive reflex to a single, maximal, dry, dynamic apnea (DYN) and how it compares to a time-matched exercise control trial (EX) or dry static apnea (SA) has not been studied. We examined the hypotheses that, compared with EX and SA, the magnitude of the 1) cardiovascular response and 2) hematological response to DYN would be greater. Cardiovascular parameters [heart rate (HR), systolic (SBP), diastolic (DBP), and mean arterial (MAP) blood pressure] were continuously collected in 23 (F = 6 females) moderate and elite freedivers, first during a maximal DYN, then during a time-matched SA and EX on a swimming ergometer in randomized order. Venous blood draws were made before and following each trial. The change in calculated oxygen saturation (DYN: -17 ± 13%, EX: -2 ± 1%, ΔSA: -2 ± 1%; P < 0.05, all comparisons) was greater during DYN compared with EX and SA. During DYN, ΔSBP (DYN: 104 ± 31 mmHg; EX: 38 ± 23 mmHg; and SA: 20 ± 11 mmHg), ΔDBP (DYN: 45 ± 12 mmHg; EX: 14 ± 10 mmHg; and SA: 15 ± 8 mmHg), and ΔMAP (DYN: 65 ± 17 mmHg; EX: 22 ± 13 mmHg; and SA: 16 ± 9 mmHg) were increased compared with EX and SA, while ΔHR was greater during EX (DYN: -24 ± 23 beats/min; EX: 33 ± 13 beats/min; and SA: -1 ± 10 beats/min) than either DYN or SA (P < 0.0001, all comparisons). Females had a greater pressor response to EX (ΔSBP: 59 ± 30 mmHg; ΔDBP: 24 ± 14 mmHg; and ΔMAP: 35 ± 8 mmHg) than males (ΔSBP: 31 ± 15 mmHg; ΔDBP: 11 ± 6 mmHg; and ΔMAP: 18 ± 8 mmHg; P < 0.01, all comparisons). Together, these data indicate that DYN elicits a distinct, exaggerated cardiovascular response compared with EX or SA alone.NEW & NOTEWORTHY This study performed a dry dynamic apnea with sport-specific equipment to closely mimic the physiological demands of competition diving. We found the cardiovascular and hematological responses to dynamic apnea were more robust compared with time-matched exercise and dry static apnea control trials.

Examining emotion regulation and inflammation as predictors of maternal mental health after fetal anomaly diagnosis

ObjectiveFetal anomalies occur in approximately 3% of pregnancies and receiving the diagnosis may be a potentially traumatic experience for families. The mental health of mothers receiving diagnoses and what predicts resilience or poor mental health is understudied. Emotion regulation is an important, modifiable, transdiagnostic factor of mental health, and may be protective post-diagnosis. Evaluating biomarkers of stress, including IL-6 and Allostatic Load (AL), can also serve as early indicators of risk, indicative of early intervention. This study assessed whether reappraisal, suppression, IL-6, and AL was associated with mental health outcomes and resilience in women after receiving a fetal anomaly diagnosis. MethodsPregnant women (N=108) presenting to a fetal concerns clinic for initial consultation completed measures of emotion regulation (i.e., reappraisal and suppression), depression, anxiety, posttraumatic stress symptoms, and resilience between 2019–2022. A blood draw was used to assess IL-6 and create composite allostatic load measure including: IL-6, blood pressure, heart rate, glucose, cortisol, and body mass index. ResultsLinear regressions controlling for age, gestational age, and perceived fetal diagnosis severity, demonstrated that IL-6 was negatively associated with resilience and positively associated with depression. Reappraisal was positively associated to resilience and negatively associated with depression, anxiety, and PTSD, whereas state insurance status was positively associated to anxiety and PTS symptoms. Suppression and allostatic load were not significant. ConclusionsWomen experiencing fetal anomaly diagnosis represent an understudied population with unaddressed mental health needs. Reappraisal serves as not only a protective factor, but one that can be enhanced to promote maternal resilience and mental health. Furthermore, elevated IL-6 may be a critical early indicator of potential intervention needs among women who are pregnant, to mitigate negative psychological states and enhance resilience.

Selective red blood cell depletion by apheresis in sheep causes severe normovolemic anemia

Background: The setting of normovolemic anemia is required for a variety of research applications, such as testing of novel medication for anemia treatment. Unfortunately, large animal models using full blood draw and replenishment with balanced electrolyte solution (BES) lead to bleeding complications, as coagulation factors and platelets are also drawn. We therefore aimed to establish a model of selective red blood cell (RBC) depletion to the main endpoint of hemoglobin (Hgb) levels of 4–6 g dL−1 using apheresis in sheep. Methods: In vitro experiments were performed first to establish the apheresis protocol. In vivo, anesthetized ewes underwent a sham protocol without apheresis (n = 5) or apheresis (n = 4). Both groups were observed for the following six hours at a defined starting point (BE0) to compare Hgb, hematocrit (Hct), coagulation and clinical parameters. For statistical analysis, unpaired t-test with Welch`s correction was used. Results: Hgb levels were effectively decreased by 51 % to mean Hgb of 4.4 g dL−1 in the apheresis group compared to 9.1 g dL−1 in sham (*p < 0.0001). Hct (11.2% vs 25.1 %, *p = 0.01) and RBCs (3.7 vs 8.2 × 106/µl, *p = 0.003) also decreased. The relative number of platelets compared to baseline was different (55.6 ± 10.6% vs. 100 ± 0 %, *p = 0.004), but no hemorrhage was observed. White blood cells (WBCs), lactate, prothrombin ratio and activated partial thromboplastin time (aPTT) remained within similar ranges. Conclusions: Critical normovolemic anemia without bleeding complications was successfully reached by selective RBC depletion in sheep. Investigations of physiological adaptations to severe anemia and pharmaceutical testing can be performed in large animals with depleted RBCs.

Recombinant erythropoietin for the treatment of iron deficiency anemia in pregnancy: A systematic review.

Treatment options for severe, refractory iron deficiency anemia are limited in pregnancy. To review the available literature on the use of recombinant erythropoietin in the treatment of iron deficiency anemia in pregnancy. An electronic search of seven databases from inception to March 2022 was performed using a combination of keywords. We included all randomized controlled or observational studies of pregnant patients with iron deficiency anemia who received recombinant erythropoietin or control. The primary outcome was a change in hematologic parameters (hemoglobin or hematocrit) after treatment. Studies were appraised using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Data were summarized using narrative synthesis and descriptive statistics as appropriate. This study was registered with PROSPERO, CRD42022313328. Of 234 studies screened, five studies met the inclusion criteria and had sufficient data for analysis (n = 103 recombinant erythropoietin and n = 104 controls). All patients in the intervention group received iron supplementation (intravenous or oral) in addition to recombinant erythropoietin. All patients in the control group received iron supplementation (intravenous or oral) alone. As the result of variance between studies in inclusion criteria, the timing of repeat blood draws, and data reporting, a meta-analysis could not be performed. Three studies found that serial recombinant erythropoietin combined with iron supplementation was more effective at raising hematologic laboratory parameters (hemoglobin or hematocrit) than iron alone. One study reported no difference in hemoglobin or hematocrit levels between groups at day 28. However, patients in this study only received one dose of recombinant erythropoietin, whereas those in the other studies received serial doses. Another study also found no difference in hemoglobin levels by day 28, but patients in the recombinant erythropoietin group had lower hemoglobin levels at baseline and a more rapid rise in hemoglobin than iron alone. This is demonstrated by a more significant rise in hemoglobin at day 11 in the recombinant erythropoietin group than in the control group. Serial recombinant erythropoietin administration and iron supplementation may be more effective at treating refractory iron deficiency anemia in pregnancy than iron supplementation alone.