Feasibility, reliability and satisfaction of (automated) capillary carcinoembryonic antigen measurements for future home-based blood sampling: the prospective CASA-I study.

AIM: Follow-up for colorectal cancer (CRC) necessitates regular monitoring of carcinoembryonic antigen (CEA) at the hospital. Capillary home-based blood collection, including minimally invasive techniques such as lancet sampling or an automated upper arm device (TAP-II), has the potential to replace a significant portion of hospital-based blood sampling, thereby enhancing self-reliance and quality of life. The objectives of this study were to assess the feasibility, reliability and preference for CEA blood collection. METHODS: Baseline venous and capillary (by lancet and TAP-II) blood samples were collected from 102 participants, including 20 CRC patients with elevated CEA levels, 60 CRC patients undergoing postoperative outpatient monitoring and 20 healthy volunteers. The second group performed capillary blood collections at home on two consecutive follow-up appointments and subsequently sent them to the hospital. Satisfaction was assessed via patient reported outcome measures on pain, burden, ease of use and preference. RESULTS: The Pearson's correlation test of all usable samples resulted in a linear coefficient of 0.998 (95% CI 0.997-0.998) for the TAP-II method and 0.997 (95% CI 0.996-0.998) for the lancet method, both compared to venipuncture. Following the initial blood collection, 86% of the participants (n = 102) favoured the TAP-II, rating it as the least painful and burdensome option. After two home-based blood samples, the preference for the TAP-II method persisted, with 64% of the patients endorsing its use. CONCLUSION: This study demonstrated the feasibility of home-based capillary sampling of CEA. The TAP-II blood collection is the most reliable method and is preferred by patients over venipuncture and lancet sampling.

Impact of Blood Sampling Methods on Blood Loss and Transfusion After Pediatric Cardiac Surgery: An Observational Study.

OBJECTIVES: The aims of this study were to assess the impact of the closed-loop sampling method on blood loss and the need for blood transfusion in pediatric patients following cardiac surgery. DESIGN: Retrospective observational study. SETTING: A single tertiary center. PARTICIPANTS: All pediatric patients younger than 4 years old who were admitted to the pediatric intensive care unit (PICU) after cardiac surgery were enrolled. The study included 100 pediatric patients in the conservative (postimplementation) group and 43 pediatric patients in the nonconservative group (preimplementation). INTERVENTIONS: Observational. MEASUREMENTS: The primary outcome was the volume of blood loss during the PICU follow-up period. The secondary outcomes were the requirement for blood transfusion in each group, duration of mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, and mortality. MAIN RESULTS: In the conservative (postimplementation) group, blood loss during the follow-up period was 0.67 (0.33-1.16) mL/kg/d, while it was 0.95 (0.50-2.30) mL/kg/d in the nonconservative (preimplementation) group, demonstrating a significant reduction in blood loss in the conservative group (p = 0.012). The groups showed no significant differences in terms of the required blood transfusion volume postoperatively during the first 24 hours, first 48 hours, or after 48 hours (p = 0.061, 0.536, 0.442, respectively). The frequency of blood transfusion was comparable between the groups during the first 24 hours, first 48 hours, or after 48 hours postoperatively (p = 0.277, 0.639, 0.075, respectively). In addition, the groups did not show significant differences in the duration of mechanical ventilation, length of ICU stay, length of hospital stay, or mortality. CONCLUSIONS: The closed-loop sampling method can be efficient in decreasing blood loss during postoperative PICU follow-up for pediatric patients after cardiac surgeries. However, its application did not reduce the frequency or the volume of blood transfusion in these patients.

Effects of automatic heel lancet on invasiveness in neonates: A systematic review and meta-analysis.

AIM: We conducted a meta-analysis comparing the invasiveness of automatic lancet devices, which can collect adequate amount of blood at shallow puncture depths, with conventional manual lance devices (lancet or needle) to statistically identify less invasive instruments for neonatal heel lance. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, and Ichushi databases for studies comparing the invasiveness between automatic lancet and manual lancet or needle in term and preterm neonates in neonatal intensive care unit. RESULTS: This review included 9 out of 449 searched articles, with 673 neonates. Automatic lancet had significantly lower pain scores (standardised mean difference: -2.0, 95% confidence interval: -3.3 to -0.7), heart rate (mean difference: -8.0, 95% confidence interval: -13.8 to -2.1), cry duration (mean difference: -21.5, 95% confidence interval: -32.5 to -10.4), number of punctures (mean difference: -0.6, 95% confidence interval: -1.1 to -0.2), and duration of procedures (mean difference: -37.7, 95% confidence interval: -75.2 to -0.2) than manual lancet or needle. Furthermore, peripheral oxygen saturation was significantly higher in automatic lancet than in manual lancet or needle (mean difference: 4.5, 95% confidence interval: 0.5-8.5). CONCLUSION: Automatic heel lancet devices were less invasive than manual heel lance devices (lancet or needle).

Recommendations for blood sampling in emergency departments from the European Society for Emergency Medicine (EUSEM), European Society for Emergency Nursing (EuSEN), and European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase. Executive summary.

AIM: Blood Sampling Guidelines have been developed to target European emergency medicine-related professionals involved in the blood sampling process (e.g. physicians, nurses, phlebotomists working in the ED), as well as laboratory physicians and other related professionals. The guidelines population focus on adult patients. The development of these blood sampling guidelines for the ED setting is based on the collaboration of three European scientific societies that have a role to play in the preanalytical phase process: EuSEN, EFLM, and EUSEM. The elaboration of the questions was done using the PICO procedure, literature search and appraisal was based on the GRADE methodology. The final recommendations were reviewed by an international multidisciplinary external review group. RESULTS: The document includes the elaborated recommendations for the selected sixteen questions. Three in pre-sampling, eight regarding sampling, three post-sampling, and two focus on quality assurance. In general, the quality of the evidence is very low, and the strength of the recommendation in all the questions has been rated as weak. The working group in four questions elaborate the recommendations, based mainly on group experience, rating as good practice. CONCLUSIONS: The multidisciplinary working group was considered one of the major contributors to this guideline. The lack of quality information highlights the need for research in this area of the patient care process. The peculiarities of the emergency medical areas need specific considerations to minimise the possibility of errors in the preanalytical phase.

Umbilical Cord Blood as an Alternative to Neonatal Blood for Complete Blood Count: A Comparison Study.

OBJECTIVE: To assess concordance between umbilical cord blood (UCB) and neonatal blood (NB) laboratory test results at birth. STUDY DESIGN: This retrospective study considered very preterm neonates (<32 weeks' gestational age) admitted to a tertiary neonatal intensive care unit from 2012 to 2023. Inclusion criteria required neonates with a complete blood count measured in both UCB and NB drawn within 2 hours after birth. Median hemoglobin (Hb) and hematocrit (Hct) concentrations were compared between UCB (venous samples) and NB (venous, arterial, or capillary samples). RESULTS: A total of 432 neonates with paired UCB and NB values were included in the study. Hb concentration in UCB was 14.7 g/dL (IQR 13.5-16.1 g/dL) compared with 14.8 g/dL (IQR 12.6-19.3 g/dL) in venous NB samples, 13.9 g/dL (IQR 12.9-15.3 g/dL) in arterial NB and 18.7 g/dL (IQR 16.6-20.8 g/dL) in capillary NB. The regression equation showed a correction factor of 1.08 for converting Hb values from UCB to venous NB. Median Hct concentration in UCB was 0.45 L/L (IQR: 0.41-0.49 L/L) compared with 0.48 L/L (IQR 0.43-0.54 L/L) in venous NB, 0.42 L/L (IQR 0.38-0.45 L/L) in arterial NB and 0.57 L/L, (IQR 0.51-0.63 L/L) in capillary NB. CONCLUSIONS: Hb and Hct concentrations measured in UCB are similar to those measured in venous blood in very preterm infants and are valid alternatives for NB tests at birth. Hb and Hct concentrations in arterial and capillary NB are respectively lower and higher compared with UCB measurements.

Best practices for iatrogenic anaemia prevention in the intensive care unit: Blood-sparing techniques.

Anaemia is a common issue in patients who are admitted to intensive care units and worsens their condition throughout the stay due to the extraction of blood for diagnostic purposes. It is also well-known that an important amount of the carbon dioxide produced by health services is likely attributable to blood donation, testing and manufacture, storage or distribution of blood components. This must be taken into account to perform nursing interventions consistent with the idea of sustainable health care. In this regard, within patient blood management bundles, with the objective of minimizing the use of blood products, it is recommended to use blood-sparing techniques: small volume tubes (SVT) or closed-blood sampling devices (CBSD). Published studies before 2014 (excepting two more recent ones) have shown that by themselves, both techniques reduce drawn volume but do not decrease haemoglobin reduction and/or need of transfusion. Given the lack of cost-effectiveness studies, it may be easier to implement the use of CBSD as it does not require prior consensus on the discard volume or adaptations in the processing of laboratory tests, as is the case with SVT.

Optimal volume for the draw-and-return methods to enhance activated partial thromboplastin time ratio accuracy in hemodialysis patients with central venous catheters.

Background: Significant errors of activated partial thromboplastin time (aPTT) ratio were frequently observed in blood sampling from central venous dialysis catheter (CVC) of hemodialysis (HD) patients. Following the draw-and-return methods, initial blood withdrawal from the catheter before sampling can reduce the error, but the optimal withdrawal volume remains undetermined. Aim: The objective of this study is to determine the optimal blood withdrawal volume for the draw-and-return methods to improve aPTT ratio accuracy in hemodialysis patients with CVC. Methods: A prospective study was conducted in patients receiving HD via CVC. Four blood samples were collected from each patient, involving a peripheral venipuncture and three draw-and-return samples (10 ml, 20 ml and 25 ml groups). The aPTT ratio of a peripheral sample was used as a reference to determine the aPTT ratio accuracy for each draw-and-return group. Subsequently, the agreement was illustrated using modified Bland-Altman plot. Results: A total of 1,000 samples were obtained from 250 patients. The patients had a mean age of 59.6 ± 15.4 years, with 17.2% using citrate as the CVC's locking agent. The adjusted accuracies of the aPTT ratio varied significantly among the three withdrawal volumes (p-value <0.001). The 25 ml group demonstrated the highest accuracy (43.2%; 95%CI, 38.0-48.4), followed by the 20 ml group (30.0%; 95%CI, 24.9-35.2), and the 10 ml group (18.0%; 95%CI, 12.8-23.2). Additionally, using citrate as a locking agent provided more than 80.0% aPTT ratio accuracy, whereas heparin demonstrated inferior accuracy even in the 25 ml withdrawal group. Conclusion: The optimal blood withdraw volume for the draw-and-return methods concluded at 20 ml for citrate locked-CVC and 25 ml for heparin which significantly improved aPTT ratio accuracies. Applying citrate as a locking agent provides clear benefits for aPTT ratio monitoring, while peripheral venipuncture is recommended in cases of heparin-locked CVC.

Use of an expert elicitation methodology to compare welfare impacts of two approaches for blood sampling European badgers (Meles meles) in the field.

In the UK and Republic of Ireland, the European badger (Meles meles) is considered the most significant wildlife reservoir of the bacterium Mycobacterium bovis, the cause of bovine tuberculosis (bTB). To expand options for bTB surveillance and disease control, the Animal and Plant Health Agency developed a bespoke physical restraint cage to facilitate collection of a small blood sample from a restrained, conscious badger in the field. A key step, prior to pursuing operational deployment of the novel restraint cage, was an assessment of the relative welfare impacts of the approach. We used an established welfare assessment model to elicit expert opinion during two workshops to compare the impacts of the restraint cage approach with the only current alternative for obtaining blood samples from badgers in the field, which involves administration of a general anaesthetic. Eleven panellists participated in the workshops, comprising experts in the fields of wildlife biology, animal welfare science, badger capture and sampling, and veterinary science. Both approaches were assessed to have negative welfare impacts, although in neither case were overall welfare scores higher than intermediate, never exceeding 5-6 out of a possible 8. Based on our assessments, the restraint cage approach is no worse for welfare compared to using general anaesthesia and possibly has a lower overall negative impact on badger welfare. Our results can be used to integrate consideration of badger welfare alongside other factors, including financial cost and efficiency, when selecting a field method for blood sampling free-living badgers.

Contribution of fetal blood sampling to determining the prognosis of congenital cytomegalovirus infections: a case-cohort study in Switzerland.

BACKGROUND: Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5% to 1.0% of live births in Europe. Congenital cytomegalovirus infection can be diagnosed during pregnancy by viral DNA amplification in the amniotic fluid, but the prognosis of fetuses without severe brain abnormalities remains difficult to establish on the basis of prenatal imaging alone. OBJECTIVE: To identify predictors of moderate to severe symptomatic cytomegalovirus infection among fetal blood parameters and to propose an algorithm on the basis of these parameters and on prenatal imaging that would provide the best positive and negative predictive values. STUDY DESIGN: Fetal blood sampling at 21-28 weeks gestation was performed in fetuses with congenital cytomegalovirus infection confirmed by amniocentesis after maternal infection in the first-trimester or periconceptional period. We compared the levels of hemoglobin, thrombocytes, γ-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, ß2-microglobulin, immunoglobulins G and M, and cytomegalovirus DNA viral loads in amniotic fluid and fetal blood between those with moderate to severe symptomatic infection and those with asymptomatic to mild infection (median follow-up of 36 months for live births). RESULTS: Among 58 fetuses included, 25 (43%) had a moderate to severe symptomatic infection: 16 with severe cerebral abnormalities, 5 with multiple signs or symptoms at birth, 2 with bilateral sensorineural hearing loss, and 2 with neurodevelopmental delay. The values of thrombocytes, aspartate aminotransferase, ß2 microglobulin, Immunoglobulin M, and cytomegalovirus viral loads differed significantly between fetuses with moderate to severe symptomatic infection and those with asymptomatic to mild infection. The optimal strategy to predict moderate to severe symptomatic infection was to first perform fetal brain imaging, followed by fetal blood sampling with the following cutoffs: thrombocytes <120,000/mL, viremia ≥5 log10/mL, and ß2 microglobulin ≥12 mg/L). This recursive algorithm had a negative predictive value of 100% for moderately to severely symptomatic infection. CONCLUSION: The combination of thrombocytes, ß2-microglobulin, and cytomegalovirus viral load in fetal blood can be used for prognosis determination, particularly in cytomegalovirus-infected fetuses without severe brain abnormalities at the time of prenatal diagnosis. Future studies should evaluate whether these parameters remain useful in infected fetuses who have been treated with valacyclovir before fetal blood sampling.

Prototype and evaluation of automatic fingertip-blood-sampling system that uses fingertip blood-vessel images to determine puncture position.

We are developing an automatic fingertip-blood-sampling system to reduce the burden on trained medical personnel. For this system to withdraw a consistent volume of sampled blood for blood tests, we developed a mechanism for our system to select and puncture the vicinity of a large blood vessel from the blood-vessel image of an individual's fingertip. We call this mechanism the fingertip-vessel-puncture mechanism. From the results of an experiment in which the fingertips of 20 individuals (men and women in their 20 s to 60 s) were manually punctured at near and far locations from the blood vessel selected with our mechanism, the following conclusions were obtained. The fingertip-vessel-puncture mechanism tends to increase the volume of sampled blood, thus is effective in sampling more than 650 µL of blood for automatic blood analyzers. It was also found that it is more effective in increasing the volume of sampled blood in the men and those who were younger.

Are we ready for widespread implementation of lactate POCT in fetal blood sampling? An analytical and clinical verification of the novel statstrip POCT analyzer.

Objectives: Currently, pH values are used in fetal scalp blood sampling as a parameter to rule out fetal distress during the delivery. Due to a high number of pre-analytical errors in pH measurements, lactate measurement is already extensively examined as an alternative. Our objectives were to confirm the analytical performance of the StatStrip lactate POCT analyzer and to compare pH and lactate as a marker of fetal distress. Design: and methods: Fetal blood scalp, umbilical and arterial blood test results (n = 100) were analyzed to compare the current POC blood gas analyzer including lactate (iSTAT-1) with the new POCT analyzer (StatStrip) to test the analytical performance. Furthermore, in all fetal scalp blood tests with a lactate en pH measurement from 2021 to 2023, clinical delivery data was collected to perform a clinical verification. Results: The lactate concentration on the StatStrip analyzer correlated well with the iSTAT-1 (Pearson's r ≥ 0.95). 73 Fetal scalp blood tests showed 18% discrepant results when comparing pH and lactate with regard to fetal distress and consequent delivery intervention. Lactate showed more false positive results than pH (4 versus 1), but no false negatives as opposed to pH (0 versus 1). Conclusions: The lactate Statstrip and iSTAT-1 POCT analyzers were analytically equivalent. The clinical verification study showed that lactate is a good predictor of fetal distress, although more false positive results were found in our limited dataset. However, unnecessary interventions due to failed pH measurements might be prevented when a lactate measurement is introduced.

Comparative Efficacy of Breastfeeding or Feeding of Breast Milk on Blood Sampling Pain Relief in Full-Term Neonates: A Systematic Review and Meta-Analysis.

Objectives: To evaluate the efficacy of breastfeeding or feeding of breast milk in reducing blood sampling pain in full-term neonates by comparing with other intervention measures. Methods: Related literature was searched from PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials (Central). Only randomized controlled trials (RCTs), which reported the effect of breastfeeding or feeding of breast milk on blood sampling pain in full-term neonates, were eligible. The primary outcome was set as pain score on scales, and the secondary outcomes as physiological and behavioral indicators. The risk of bias in included studies was assessed by the Cochrane Collaboration's tool. Data analysis was performed using RevMan 5.4.1. Main Results: A total of 17 RCTs were included. Breastfeeding showed a stronger effectiveness in reducing blood sampling pain, compared with nonintervention, placebo, mother's holding, breast milk odor, mother's heartbeat, music therapy, skin-to-skin, and Eutectic Mixture of Local Anesthetics ointment. However, the efficacy of glucose or sucrose (12.5%-30% concentration) seems better than breastfeeding. When compared with other interventions, feeding of breast milk yielded different results. Its effect was only stronger than placebo (sterile water or distilled water), massage, or nonintervention. Conclusions: Breastfeeding might be effective for alleviating blood sampling pain in full-term neonates. Its effect is second only to that of glucose/sucrose. The efficacy of feeding of breast milk in reducing blood sampling pain in full-term neonates might not be guaranteed.

How to obtain the image-derived blood concentration from 89Zr-immuno-PET scans.

BACKGROUND: PET scans using zirconium-89 labelled monoclonal antibodies (89Zr-mAbs), known as 89Zr-immuno-PET, are made to measure uptake in tumour and organ tissue. Uptake is related to the supply of 89Zr-mAbs in the blood. Measuring activity concentrations in blood, however, requires invasive blood sampling. This study aims to identify the best delineation strategy to obtain the image-derived blood concentration (IDBC) from 89Zr-immuno-PET scans. METHODS: PET imaging and blood sampling of two 89Zr-mAbs were included, 89Zr-cetuximab and 89Zr-durvalumab. For seven patients receiving 89Zr-cetuximab, PET scans on 1-2 h, 2 and 6 days post-injection (p.i.) were analysed. Five patients received three injections of 89Zr-durvalumab. The scanning protocol for the first two injections consisted of PET scanning on 2, 5 and 7 days p.i. and for the third injection only on 7 days p.i. Blood samples were drawn with every PET scan and the sample-derived blood concentration (SDBC) was used as gold standard for the IDBC. According to an in-house developed standard operating procedure, the aortic arch, ascending aorta, descending aorta and left ventricle were delineated. Bland-Altman analyses were performed to assess the bias (mean difference) and variability (1.96 times the standard deviation of the differences) between IDBC and SDBC. RESULTS: Overall, the activity concentration obtained from the IDBC was lower than from the SDBC. When comparing IDBC with SDBC, variability was smallest for the ascending aorta (20.3% and 17.0% for 89Zr-cetuximab and 89Zr-durvalumab, respectively). Variability for the other regions ranged between 17.9 and 30.8%. Bias for the ascending aorta was - 10.9% and - 11.4% for 89Zr-cetuximab and 89Zr-durvalumab, respectively. CONCLUSIONS: Image-derived blood concentrations should be obtained from delineating the ascending aorta in 89Zr-immuno-PET scans, as this results in the lowest variability with respect to sample-derived blood concentrations.

[Analysis of indocyanine green plasma disappearance rate in clinical practice]. / Vybor metodiki opredeleniya skorosti plazmennoi eliminatsii indotsianina zelenogo v klinicheskoi praktike.

OBJECTIVE: To justify the optimal method for determining indocyanine green plasma disappearance rate (PDRICG). MATERIAL AND METHODS: We analyzed PDRICG in intensive care units. Indocyanine green was administered intravenously at a dose of 0.25 mg/kg. PDRICG was analyzed simultaneously by using of three methods: 1) PDD (PiCCO2 LiMON device), 2) SBS with analysis of plasma samples on precise spectrophotometer, 3) SBS with analysis of plasma samples on simple experimental photometer. RESULTS: PDD method was used for 346 PDRICG tests in 256 patients. Of these, 14.3% of measurements were erroneous. Paired tests using PDD and SBS methods were performed in 299 cases. SBS method resulted erroneous data in 0.6% of cases. Certain correlation (r=0.79, p<0.001) was found between the reference method (SBS with spectrophotometry) and the PDD method. Bland-Altman plot for these two methods showed that proportional bias of mean difference was caused by extremely high PDRICG of the PDD method (for example, more than 30%/min). Comparison of two SBS variants (spectrophotometer and experimental photometer) revealed good correlation (r=0.91, p<0.001). CONCLUSION: SBS method for measuring PDRICG ensures accurate results under mechanical interferences in patients with impaired capillary blood flow. This eliminates the need for redo measurement. Duplication of the PDD and SBS methods is recommended when repeating the test is not possible (organ donors).

The influence of dead space in blood sampling needle on FVIII level and pharmacokinetic profiles in children with hemophilia.

OBJECTIVE: To investigate the influence of the dead space in disposable blood sampling needle on activated partial thromboplastin time (APTT), FVIII level and pharmacokinetic (PK) profiles in children with hemophilia. METHODS: Children (<18 years) with severe hemophilia A were enrolled. After three days' washout-period, blood samples were collected at pre-dose, 1 h, 3 h, 9 h, 24 h and 48 h post-infusion. At each timepoint, two 2 mL vacuum tubes with 3.2% trisodium citrate were used. The first tube was signed as 'non-standard' (NS) and the second tube was signed as 'standard' (S). FVIII activities were evaluated by one-stage assay. WAPPS-Hemo was used to generate PK profiles like half-life time (t1/2), clearance (CL), trough level and time to 1, 2 and 5IU/dL after a dose of 50 ± 10IU/dL. The FVIII activities at 9 h and 24 h post-infusion were put into WAPPS and thus brought four combinations by true or biased FVIII level that used. RESULT: Compared with standard-collected blood samples, prolonged APTT results (P-values < 0.01) and decreased FVIII activity (P-values < 0.05) were revealed in those non-standard blood samples. The corresponding bias was in positive relation to both APTT-S (r = 0.44, P < 0.0001) and FVIII-S level(r = 0.68, P < 0.001). The FVIII bias percentage got larger as FVIII-S level reduced (r = -0.24, P < 0.01). During the four combinations of FVIII activity at 9 h and 24 h, statistically longer t1/2, lower CL and longer time to 1, 2 or 5IU/dL were observed in 9H-S&24H-S group and 9H-NS&24H-S group. CONCLUSION: While using vacuum tubes for clotting indicators and PK profiles, the dead space of blood sampling needle should be eliminated in advance.

Adherence to Background Antipsychotic and Pimavanserin in Patients with Schizophrenia: Post Hoc Analyses from the ENHANCE and ADVANCE Studies.

Background: In patients with schizophrenia, study design to optimize adherence and objective measurement of adherence is critical for interpreting results. Two randomized, double-blind studies evaluating adjunctive pimavanserin in patients with schizophrenia who received stable antipsychotic treatment included measures to encourage and assess treatment adherence. Objective: This post hoc analysis evaluated adherence levels achieved in the Phase III ENHANCE study (NCT02970292) and the Phase II ADVANCE study (NCT02970305). Methods: Blood levels of participants receiving adjunctive treatment with pimavanserin or placebo added to their ongoing antipsychotic medication were tested and evaluated regularly throughout both studies. For both the background antipsychotic and pimavanserin, treatment adherence was defined as a blood sample test result above the lower limit of quantification. Results: Overall, 392 of 633 screened patients and 403 of 608 screened patients were in the safety populations in ENHANCE and ADVANCE, respectively. In ENHANCE, at weeks 1, 3, and 6/early termination (ET), the adherence rates remained ≥ 95.1% for the background antipsychotic in both pimavanserin and placebo treatment groups and ≥ 96.8% for pimavanserin. In ADVANCE, high adherence rates (≥90.6%) with the background antipsychotic (for both treatment groups) and pimavanserin (≥95.0%) were observed at weeks 2, 8, 14, and 26/ET. Conclusion: Rigorous screening was performed to exclude patients not adherent to their background antipsychotic before enrollment and to pimavanserin during study visits by using regular blood sampling. Mandatory caregiver participation further supported adherence to study treatment and procedures. These efforts may have contributed to the high levels of adherence to both background antipsychotic and pimavanserin reported in ENHANCE and ADVANCE.

Fetal Anemia: Determinants and Perinatal Outcomes according to the Method of Intrauterine Blood Transfusion.

INTRODUCTION: Fetal anemia from hemolytic disease treated by intrauterine transfusion (IUT) can be performed by intraperitoneal, intracardiac, and intravascular transfusion (IVT). Objective of our study was to compare different transfusion techniques. METHODS: Retrospective review of IUT secondary to red cell alloimmunization was conducted at eight international centers from 2012 to 2020. Severe anemia suspected if middle cerebral artery peaks systolic velocity ≥1.5 multiples of the median. Demographic, delivery, and postnatal variables were analyzed. RESULTS: Total of 344 procedures, 325 IVT and 19 other techniques (non-IVT) included. No difference in demographics, history of stillbirth (20.5 vs. 15.8%, p = 0.7), prior pregnancy IUT (25.6 vs. 31.6%, p = 0.5) or neonatal transfusion (36.1 vs. 43.8%, p = 0.5). At first IUT, non-IVT had higher hydrops (42.1% vs. 20.4%, p = 0.03), lower starting hematocrit (13.3% [±6] vs. 17.7% [±8.2], p = 0.04), and trend toward lower gestational age (24.6 [20.1-27] vs. 26.4 [23.2-29.6] weeks, p = 0.08). No difference in birthweight, neonatal phototherapy, exchange, or simple transfusion was observed. CONCLUSION: This is one of the largest studies comparing techniques to treat fetal anemia. IVT was most performed, other techniques were more likely performed in hydrops, and lower starting hematocrit was seen. Neither technique affected outcomes. This study may suggest that physician's experience may be the strongest contributor of outcomes.

Re-evaluating fetal scalp pH thresholds: An examination of fetal pH variations during labor.

INTRODUCTION: Since the 1970s, fetal scalp blood sampling (FSBS) has been used as a second-line test of the acid-base status of the fetus to evaluate fetal well-being during labor. The commonly employed thresholds that delineate normal pH (>7.25), subnormal (7.20-7.25), and pathological pH (<7.20) guide clinical decisions. However, these experienced-based thresholds, based on observations and common sense, have yet to be confirmed. The aim of the study was to investigate if pH drop rate accelerates at the common thresholds (7.25 and 7.20) and to explore the possibility of identifying more accurate thresholds. MATERIAL AND METHODS: A retrospective study was conducted at a tertiary maternity hospital between June 2017 and July 2021. Patients with at least one FSBS during labor for category II fetal heart rate and delivery of a singleton cephalic infant were included. The rate of change in pH value between consecutive samples for each patient was calculated and plotted as a function of pH value. Linear regression models were used to model the evolution of the pH drop rate estimating slope and standard errors across predefined pH intervals. Exploration of alternative pH action thresholds was conducted. To explore the independence of the association between pH value and pH drop rate, multiple linear regression adjusted on age, body mass index, parity, oxytocin stimulation and suspected small for gestational age was performed. RESULTS: We included 2047 patients with at least one FSBS (total FSBS 3467); with 2047 umbilical cord blood pH, and a total of 5514 pH samples. Median pH values were 7.29 1 h before delivery, 7.26 30 min before delivery. The pH drop was slow between 7.40 and 7.30, then became more pronounced, with median rates of 0.0005 units/min at 7.25 and 0.0013 units/min at 7.20. Out of the alternative pH thresholds, 7.26 and 7.20 demonstrated the best alignment with our dataset. Multiple linear regression revealed that only pH value was significantly associated to the rate of pH change. CONCLUSIONS: Our study confirms the validity and reliability of current guideline thresholds for fetal scalp pH in category II fetal heart rate.

Maternal Risk Factors and Their Effect on Outcome and Procedure-Related Complications in Cordocentesis: A Multicenter Retrospective Study.

BACKGROUND: Cordocentesis is used in clinical situations in which lower-risk diagnostic procedures do not deliver the desired results. The aim of this study was to evaluate the risk for procedure-related complications and fetal loss in correlation to maternal risk factors. METHODS: This is a multicenter retrospective study investigating the complications, risk factors and perinatal outcome of diagnostic cordocentesis between 1998 and 2019 in three different centers. RESULTS: A total of 1806 cordocenteses were performed and procedure-related complications (IUFD within 48 h, contractions, bradycardia, unsuccessful puncture, chorioamniotic separation) were noted in 1.6% of cases. Fetuses with chromosomal aberrations, intrauterine growth restriction and hydropic fetuses had a significantly higher rate of fetal loss compared to other indications. Fetal blood sampling (FBS) performed before 17+0 weeks of gestation was associated with a higher risk of procedure-related complications. Maternal BMI ≥ 40 increased the risk for fetal loss, whereas maternal age, number of previous miscarriages, number of previous abortions, history of vaginal bleeding or nicotine abuse did not affect the risk for complications or overall fetal loss rate. CONCLUSIONS: In the hands of experienced operators, FBS is a safe way to further fetal diagnostics, and the risk of complications is low.

An update on the use of image-derived input functions for human PET studies: new hopes or old illusions?

BACKGROUND: The need for arterial blood data in quantitative PET research limits the wider usability of this imaging method in clinical research settings. Image-derived input function (IDIF) approaches have been proposed as a cost-effective and non-invasive alternative to gold-standard arterial sampling. However, this approach comes with its own limitations-partial volume effects and radiometabolite correction among the most important-and varying rates of success, and the use of IDIF for brain PET has been particularly troublesome. MAIN BODY: This paper summarizes the limitations of IDIF methods for quantitative PET imaging and discusses some of the advances that may make IDIF extraction more reliable. The introduction of automated pipelines (both commercial and open-source) for clinical PET scanners is discussed as a way to improve the reliability of IDIF approaches and their utility for quantitative purposes. Survey data gathered from the PET community are then presented to understand whether the field's opinion of the usefulness and validity of IDIF is improving. Finally, as the introduction of next-generation PET scanners with long axial fields of view, ultra-high sensitivity, and improved spatial and temporal resolution, has also brought IDIF methods back into the spotlight, a discussion of the possibilities offered by these state-of-the-art scanners-inclusion of large vessels, less partial volume in small vessels, better description of the full IDIF kinetics, whole-body modeling of radiometabolite production-is included, providing a pathway for future use of IDIF. CONCLUSION: Improvements in PET scanner technology and software for automated IDIF extraction may allow to solve some of the major limitations associated with IDIF, such as partial volume effects and poor temporal sampling, with the exciting potential for accurate estimation of single kinetic rates. Nevertheless, until individualized radiometabolite correction can be performed effectively, IDIF approaches remain confined at best to a few tracers.