A survey about the practice of regional anesthesia in Manchester and Lancashire.

INTRODUCTION: In 2021, the UK Royal College of Anaesthetists published an updated curriculum which outlines specific peripheral nerve blocks in which all anesthetists must achieve competency during their training. Little is known about which nerve blocks anesthetists in the UK can perform, nor which techniques they use to perform them. METHODS: We conducted a survey of anesthetists in North West England to discover their experience in anesthesia, which nerve blocks they can perform, and which techniques they use to perform them. RESULTS: Overall, 195 responses were received. Seventy-nine respondents (44%) preferred to perform nerve blocks on anesthetized patients, 70 (40%) preferred to perform nerve blocks with the patient awake with no sedation. One hundred and thirty-seven (85%) respondents used ultrasound only to localize nerves when performing a block. Among consultant respondents, 21 (19%) were unable to perform any upper limb block, and 48 (44%) were unable to perform any block of the thorax, both are a required competency of trainees under the 2021 curriculum. DISCUSSION: Trainees may struggle to achieve the required competencies of the new curriculum given many consultants are also unable to perform them. A structured placement in regional anesthetic training in each stage of training could help improve the acquisition of skills and knowledge among trainees. Further studies are needed to assess the ability of anesthetists nationwide in regional anesthesia.

Omadacycline efficacy in the hollow fibre system model of pulmonary Mycobacterium avium complex and potency at clinically attainable doses.

OBJECTIVES: The standard of care (SOC) for the treatment of pulmonary Mycobacterium avium complex (MAC) disease (clarithromycin, rifabutin, and ethambutol) achieves sustained sputum conversion rates of only 54%. Thus, new treatments should be prioritized. METHODS: We identified the omadacycline MIC against one laboratory MAC strain and calculated drug half life in solution, which we compared with measured MAC doubling times. Next, we performed an omadacycline hollow fibre system model of intracellular MAC (HFS-MAC) exposure-effect study, as well as the three-drug SOC, using pharmacokinetics achieved in patient lung lesions. Data was analysed using bacterial kill slopes (γ-slopes) and inhibitory sigmoid Emax bacterial burden versus exposure analyses. Monte Carlo experiments (MCE) were used to identify the optimal omadacycline clinical dose. RESULTS: Omadacycline concentration declined in solution with a half-life of 27.7 h versus a MAC doubling time of 16.3 h, leading to artefactually high MICs. Exposures mediating 80% of maximal effect changed up to 8-fold depending on sampling day with bacterial burden versus exposure analyses, while γ-slope-based analyses gave a single robust estimate. The highest omadacycline monotherapy γ-slope was -0.114 (95% CI: -0.141 to -0.087) (r2 = 0.98) versus -0.114 (95% CI: -0.133 to -0.094) (r2 = 0.99) with the SOC. MCEs demonstrated that 450 mg of omadacycline given orally on the first 2 days followed by 300 mg daily would achieve the AUC0-24 target of 39.67 mg·h/L. CONCLUSIONS: Omadacycline may be a potential treatment option for pulmonary MAC, possibly as a back-bone treatment for a new MAC regimen and warrants future study in treatment of this disease.

Potency of the novel PolC DNA polymerase inhibitor CRS0540 in a disseminated Listeria monocytogenes intracellular hollow-fibre model.

BACKGROUND: Listeriosis is an orphan disease, which is nevertheless fatal in immunocompromised people. CRS0540 is a novel PolC DNA polymerase inhibitor that has demonstrated good in vitro and in vivo activity against Listeria monocytogenes. METHODS: Rodent-to-human allometry projection-based human population pharmacokinetics of CRS0540 were used for all studies. CRS0540 pharmacokinetics/pharmacodynamics studies in an intracellular hollow-fibre system model of disseminated listeriosis (HFS-Lister) examined the effect of eight treatment doses, administered daily over 7 days, in duplicate units. Total bacterial burden versus AUC/MIC exposures on each day were modelled using the inhibitory sigmoid Emax model, while CRS0540-resistant bacterial burden was modelled using a quadratic function. Ten thousand-subject Monte Carlo simulations were used to predict an optimal clinical dose for treatment. RESULTS: The mean CRS0540 intracellular/extracellular AUC0-24 ratio was 34.07 (standard error: 15.70) as measured in the HFS-Lister. CRS0540 demonstrated exposure-dependent bactericidal activity in the HFS-Lister, with the highest exposure killing approximately 5.0 log10 cfu/mL. The free drug AUC0-24/MIC associated with 80% of maximal kill (EC80) was 36.4. Resistance emergence versus AUC/MIC was described by a quadratic function, with resistance amplification at an AUC/MIC of 54.8 and resistance suppression at an AUC/MIC of 119. Monte Carlo simulations demonstrated that for the EC80 target, IV CRS0540 doses of 100 mg/kg achieved PTAs of >90% at MICs up to 1.0 mg/L. CONCLUSIONS: CRS0540 is a promising orphan drug candidate for listeriosis. Future PK/PD studies comparing it with penicillin, the standard of care, could lead to this drug as a new treatment in immunocompromised patients.

Phase 1 and preclinical profiling of ESM-HDAC391, a myeloid-targeted histone deacetylase inhibitor, shows enhanced pharmacology and monocytopaenia.

AIMS: To improve the tolerability and therapeutic application of histone deacetylase inhibitors (HDACi), by application of an esterase-sensitive motif (ESM), to target pharmacological activity directly to mononuclear myeloid cells expressing the processing enzyme carboxylesterase-1 (CES1). METHODS: This first-in-human study comprised single and multiple ascending dose cohorts to determine safety and tolerability. Pharmacodynamic parameters included acetylation, cytokine inhibition and intracellular concentrations of processed acid metabolite in isolated monocytes. Mechanistic work was conducted in vitro and in a CES1/Es1elo mouse strain. RESULTS: ESM-HDAC391 showed transient systemic exposure (plasma half-life of 21-30 min) but selective retention of processed acid for at least 12 hours, resulting in robust targeted mechanistic engagement (increased acetylation in monocytes plus inhibition of ex vivo stimulated cytokine production). ESM-HDAC391 was well tolerated and clinical toxicities common to non-targeted HDACi were not observed. ESM-HDAC391 treatment was accompanied by the novel finding of a dose-dependent monocyte depletion that was transient and reversible and which plateaued at 0.06 × 109 monocytes/L after repeat dosing with 20 or 40 mg. Characterisation of monocyte depletion in transgenic mice (CES1/Es1elo ) suggested that colony stimulating factor 1 receptor loss on circulating cells contributed to ESM-HDAC-mediated depletion. Further mechanistic investigations using human monocytes in vitro demonstrated HDACi-mediated change in myeloid fate through modulation of colony stimulating factor 1 receptor and downstream effects on cell differentiation. CONCLUSION: These findings demonstrate selective targeting of monocytes in humans using the ESM approach and identify monocytopaenia as a novel outcome of ESM-HDACi treatment, with implications for potential benefit of these molecules in myeloid-driven diseases.

Antenatal counselling for prospective parents whose fetus has a neurological anomaly: part 1, experiences and recommendations for service design.

Prospective parents whose fetus is diagnosed with a neurological anomaly go through a complex range of emotions. They describe their discussions of antenatal counselling from health care professionals as focusing too much on the nature of the anomaly involving unintelligible medical terminology, when what they really want is a picture of the best- and worst-case scenarios. Whilst information on the level of risk for their fetus is important, it is not the parents' primary concern. When statistics for risk are given, they may not be as well understood as the health care professionals think. This review discusses the published evidence on antenatal counselling and recommendations for explaining risk to parents of fetuses with neurological anomalies. From this data we make recommendations for the organization of antenatal counselling services.

Antenatal counselling for prospective parents whose fetus has a neurological anomaly: part 2, risks of adverse outcome in common anomalies.

After diagnosis of a fetal neurological anomaly, prospective parents want to know the best and worst-case scenarios and an estimation of the risk to their infant of having an atypical developmental outcome. The literature on developmental outcomes for fetal neurological anomalies is poor: studies are characterized by retrospective design, small sample size, often no standardized assessment of development, and differing definitions of anomalies. This review provides an aide-memoir on the risks of adverse neurodevelopmental outcome for ventriculomegaly, cortical anomalies, microcephaly, macrocephaly, agenesis of the corpus callosum, posterior fossa anomalies, and myelomeningocele, to assist healthcare professionals in counselling. The data in this review should be used alongside recommendations on counselling and service design described in part 1 to provide antenatal counselling.

Humanised effector-null FcγRIIA antibody inhibits immune complex-mediated proinflammatory responses.

OBJECTIVE: Immune complexes (ICs) play a critical role in the pathology of autoimmune diseases. The aim of this study was to generate and characterise a first-in-class anti-FcγRIIA antibody (Ab) VIB9600 (previously known as MEDI9600) that blocks IgG immune complex-mediated cellular activation for clinical development. METHODS: VIB9600 was humanised and optimised from the IV.3 Ab. Binding affinity and specificity were determined by Biacore and ELISA. Confocal microscopy, Flow Cytometry-based assays and binding competition assays were used to assess the mode of action of the antibody. In vitro cell-based assays were used to demonstrate suppression of IC-mediated inflammatory responses. In vivo target suppression and efficacy was demonstrated in FcγRIIA-transgenic mice. Single-dose pharmacokinetic (PK)/pharmacodynamic study multiple dose Good Laboratory Practice (GLP) toxicity studies were conducted in non-human primates. RESULTS: We generated a humanised effector-deficient anti-FcγRIIA antibody (VIB9600) that potently blocks autoantibody and IC-mediated proinflammatory responses. VIB9600 suppresses FcγRIIA activation by blocking ligand engagement and by internalising FcγRIIA from the cell surface. VIB9600 inhibits IC-induced type I interferons from plasmacytoid dendritic cells (involved in SLE), antineutrophil cytoplasmic antibody (ANCA)-induced production of reactive oxygen species by neutrophils (involved in ANCA-associated vasculitis) and IC-induced tumour necrosis factor α and interleukin-6 production (involved in rheumatoid arthritis). In FcγRIIA transgenic mice, VIB9600 suppressed antiplatelet antibody-induced thrombocytopaenia, acute anti-GBM Ab-induced nephritis and anticollagen Ab-induced arthritis. VIB9600 also exhibited favourable PK and safety profiles in cynomolgus monkey studies. CONCLUSIONS: VIB9600 is a specific humanised antibody antagonist of FcγRIIA with null effector function that warrants further clinical development for the treatment of IC-mediated diseases.

Diagnosis and outcome in nonhydropic fetal pleural effusions.

OBJECTIVE: To determine the outcome of all pregnancies with nonhydropic fetal pleural effusions in the Wessex region. METHOD: Data were extracted from the Wessex congenital anomaly database for the years 1994-2015 inclusive. RESULTS: Sixty-two fetuses and babies were identified giving a total prevalence of 1:9500. Eight fetuses had bilateral effusions with additional, nonhydrops anomalies, and 54 had isolated effusions. Of the isolated cases, 36 presented before 24-week gestation: 12 were unilateral and 24 bilateral. All of the unilateral effusions resolved before or soon after birth with no other diagnosis but of the bilateral cases, four (17%) had a trisomy and three (13%) a genetic or syndrome diagnosis. Eighteen isolated cases presented after 24-week gestation, six were unilateral of which one had trisomy 21 (17%), and three (50%) Noonan's or another lymphoedema syndrome. Twelve were bilateral: One had trisomy 21, one an unbalanced translocation (17%), three had Noonan's or another lymphoedema syndrome, and two an unspecified syndrome (42%) at birth. CONCLUSION: These data suggest that a chromosomal microarray should be offered to all fetuses presenting with a pleural effusion in the absence of hydrops, and Noonan's syndrome testing should be considered for those that develop after 24 weeks. AIM: To determine the outcome of all pregnancies with nonhydropic fetal pleural effusions in the Wessex region from 1994-2015.

Intrauterine death rate in gastroschisis following the introduction of an antenatal surveillance program: Retrospective observational study.

AIM: To investigate whether an antenatal surveillance protocol including ultrasound and cardiotocograph monitoring reduces intrauterine death (IUD) in cases of gastroschisis. Secondary outcomes included neonatal death rate, mode of delivery and rate of intervention before planned time of delivery. METHODS: This was a retrospective observational study of all women with antenatally diagnosed gastroschisis who were managed according to the surveillance program between 2002 and 2015 in a tertiary fetal medicine and pediatric surgical center covering the Wessex region of England. We reviewed and analyzed data from the Wessex Antenatally Detected Anomalies (WANDA) database as well as prospectively managed maternity, ultrasound and neonatal databases over the given time period. Case notes were reviewed when delivery was expedited. RESULTS: The IUD rate was 2.2%, a 58% reduction since the introduction of the surveillance protocol. Delivery was expedited in 35.4% of cases, and in 86% of these, delivery was by cesarean section. In women being induced as planned at 38 weeks, the vaginal delivery rate was 88%, and for those in spontaneous labor before 38 weeks it was 75%. CONCLUSIONS: An antenatal surveillance program appears to reduce the IUD in gastroschisis. In one-third of cases, delivery was indicated before the planned date of delivery. When expedited delivery was indicated, the chance of cesarean section was high.

Blowing Bubbles Helps Intubation.

Rocuronium is commonly used in preference to suxamethonium for rapid sequence induction in the Intensive Care Unit (ICU). We describe a patient who suffered significant neck trauma following a suicide attempt. On initial presentation to accident and emergency, he was an easy intubation with a Grade 1 view obtained at laryngoscopy. After surgery to repair his neck laceration, he was extubated and discharged from ICU. He later developed a severe aspiration pneumonia and required reintubation. After induction and paralysis with suxamethonium, the best view at laryngoscopy was a Grade 3 despite the use of different laryngoscopes. As the muscle paralysis wore off the patient began breathing. This produced bubbles in the back of the patient's pharynx which directed the clinician to the laryngeal inlet to allow successful intubation. In this case, the short duration of action of suxamethonium significantly aided intubation due to the return of spontaneous breathing by the patient.

The increasing incidence of foetal echogenic congenital lung malformations: an observational study.

OBJECTIVES: The aim of this study was to investigate the incidence of congenital lung malformations over the past 19 years. Congenital lung malformations (CLM) are a heterogeneous group of lung abnormalities. The antenatal diagnosis is important for foetal and neonatal management but there have been no studies examining whether the reported incidence of this abnormality is constant. METHODS: A retrospective cross-sectional study of cases identified from the Wessex Antenatally Detected Anomalies (WANDA) register 1994-2012. RESULTS: One hundred and thirty-three cases of CLM in 524 372 live and stillbirths were identified. All but seven were identified on antenatal ultrasound. During the early registry (1994-1998) the average incidence of CLM was 1.27 per 10,000 births. By the last 4 years (2008-2012) this had risen to 4.15 per 10,000 births, with a progressive increase during the intervening years. CONCLUSION: There was over a three-fold increase in the antenatally detected CLM in the Wessex region 1994-2012. Comparison with the antenatal detection of diaphragmatic hernia suggests that this is a true rise in incidence rather than an artefactual increase due to increased antenatal recognition secondary to improved ultrasound resolution and operator experience. These results have clinical and cost implications for practitioners of foetal medicine, neonatology and paediatric surgery services.

Foetal supraventricular tachycardia with hydrops fetalis: a role for direct intraperitoneal amiodarone.

INTRODUCTION: Persistent foetal tachyarrythmias complicated by hydrops fetalis carry a poor prognosis, with foetal death reported in excess of a quarter despite treatment. We present our experience with direct intraperitoneal amiodarone administration in eight hydropic foetuses with resistant supraventricular tachycardia. METHODS: Amiodarone was injected slowly into foetal peritoneal cavity under ultrasound guidance. All mothers were loaded with oral amiodarone before the procedure and maintained on it. The procedure was repeated guided by foetal rhythm. RESULT: All eight cases had severe hydrops with a median foetal heart rate of 255 bpm (range 240-300 bpm), and the median gestational age was 27+1 weeks (range 21-33+3 weeks) at presentation. In six cases, the average time for supraventricular tachycardia to revert to sinus rhythm from the first procedure was 11.5 days. In one case, intravascular injection of amiodarone into the umbilical vein was performed before intraperitoneal injection, which resulted in conversion to sinus rhythm sustained until delivery. In the last case, supraventricular tachycardia and severe hydrops persisted and the baby was delivered 5 days later at 34 weeks' gestation. Hydrops resolved in five foetuses with a mean resolution time of 28.4 days. The mean gestational age at delivery was 34+5 days and seven of eight cases survived beyond the neonatal period with good postnatal outcomes. CONCLUSION: Intraperitoneal administration of amiodarone is a relatively simple and effective strategy in refractory supraventricular tachycardia complicated by severe hydrops. The intraperitoneal route assures delivery of the drug to the severely hydropic foetus and enables a bolus dose to be delivered for sustained absorption.

Smartphone hearing screening with integrated quality control and data management.

OBJECTIVE: To determine if a smartphone application could be used as a calibrated screening audiometer with real-time noise monitoring for school screening using automated test sequences. DESIGN: The investigation comprised three studies. Study 1 evaluated calibration accuracy across four Samsung S5301 smartphones (Android v4.0.4) using commercial Sennheiser HD202 headphones. Study 2 involved referencing smartphone microphone sensitivity to narrowband noise intensity as measured in octave bands by a sound-level meter between 30 and 75 dB SPL (5 dB increments). Study 3 compared screening outcomes of smartphone based and conventional hearing screening. STUDY SAMPLE: Study 2: 15 normal-hearing subjects (age range, 18-22 years; all female). Study 3: 162 children (324 ears) aged 5 to 7 years. RESULTS: Smartphone calibration at 20, 30, and 40 dB was within 1 dB of recommended reference equivalent thresholds levels. Microphone calibration for noise monitoring had maximum variability across phones of 0.9, 0.6, and 2.9 dB at 1, 2, and 4 kHz, respectively, from reference intensities (30 to 75 dB SPL). Screening outcomes demonstrated no significant difference between smartphone and conventional audiometry with an overall referral rate of 4.3% and 3.7%, respectively. CONCLUSIONS: The newly developed smartphone application can be accurately calibrated for audiometry with valid real-time noise monitoring, and clinical results are comparable to conventional screening.

The implicit power of positive thinking: The effect of positive episodic simulation on implicit future expectancies.

Previous research demonstrating that positive episodic simulation enhances future expectancies has relied on explicit expectancy measures. The current study investigated the effects of episodic simulation on implicit expectancies. Using the Future Thinking Implicit Relational Assessment Procedure (FT-IRAP), participants made true/false decisions to indicate whether or not they expected positive/negative outcomes after adopting orientations consistent or inconsistent with an optimistic disposition. The outcome measure, DIRAP, was based on response time differences between consistent and inconsistent blocks. Participants then engaged in either positive simulation training, in which they imagined positive future events, or a neutral visualisation task before repeating the FT-IRAP twice following 10-minute intervals. Positive simulation training increased DIRAP scores for don't-expect-negative trials-boosting participants' readiness to affirm that negative events were unlikely to happen to them. Although findings did not generalise across all trial types, they show potential for positive simulation training to enhance implicit future expectancies.

A novel somatostatin receptor ligand for human ACTH - and GH -secreting pituitary adenomas.

OBJECTIVE: Somatostatin receptor ligands have come to play a pivotal role in the treatment of both ACTH- and GH-secreting pituitary adenomas. Clinical efficacy averages 30-50%, thus a considerable number of patients with Cushing's disease or acromegaly remain unresponsive to this therapeutic approach. HTL0030310 is a new somatostatin receptor ligand selective for subtype 5 over subtype 2, thus with a different receptor profile compared to clinical somatostatin receptor ligands. DESIGN: Assessment of the effect of HTL0030310 on hormone secretion in human ACTH- and GH-secreting pituitary adenomas in vitro. METHODS: Primary cultures from 3 ACTH-secreting and 5 GH-secreting pituitary adenomas were treated with 1, 10 and 100 nM HTL0030310 alone or with 10 nM CRH or GHRH, respectively. Parallel incubations with 10 nM pasireotide were also carried out. ACTH and GH secretion were assessed after 4 and 24 hour incubation; SSTR2, SSTR3, SSTR5, GH and POMC expression were evaluated after 24 hours. RESULTS: HTL0030310 reduced unchallenged ACTH and POMC levels up to 50% in 2 ACTH-secreting adenomas and blunted CRH-stimulated ACTH/POMC by 20-70% in all 3 specimens. A reduction in spontaneous GH secretion was observed in 4 GH-secreting adenomas and in 2 specimens during GHRH co-incubation. SSTRs expression was detected in all specimens. CONCLUSIONS: This first study on a novel somatostatin receptor 5-preferring ligand indicates that HTL0030310 can inhibit hormonal secretion in human ACTH- and GH-secreting pituitary adenomas. These findings suggest a potential new avenue for somatostatin ligands in the treatment of Cushing's disease and acromegaly.

A Randomized Phase I Study of the Anti-Interleukin-33 Antibody Tozorakimab in Healthy Adults and Patients With Chronic Obstructive Pulmonary Disease.

Tozorakimab is a human monoclonal antibody that neutralizes interleukin (IL)-33. IL-33 is a broad-acting epithelial "alarmin" cytokine upregulated in lung tissue of patients with chronic obstructive pulmonary disease (COPD). This first-in-human, phase I, randomized, double-blind, placebo-controlled study (NCT03096795) evaluated the safety, tolerability, pharmacokinetics (PKs), immunogenicity, target engagement, and pharmacodynamics (PDs) of tozorakimab. This was a 3-part study. In part 1, 56 healthy participants with a history of mild atopy received single escalating doses of either intravenous or subcutaneous tozorakimab or placebo. In part 2, 24 patients with mild COPD received multiple ascending doses of subcutaneous tozorakimab or placebo. In part 3, 8 healthy Japanese participants received a single intravenous dose of tozorakimab or placebo. The safety data collected included treatment-emergent adverse events (TEAEs), vital signs, and clinical laboratory parameters. Biological samples for PKs, immunogenicity, target engagement, and PD biomarker analyses were collected. No meaningful differences in the frequencies of TEAEs were observed between the tozorakimab and placebo arms. Three tozorakimab-treated participants with COPD experienced treatment-emergent serious adverse events. Subcutaneous or intravenous tozorakimab demonstrated linear, time-independent PKs with a mean half-life of 11.7-17.3 days. Treatment-emergent anti-drug antibody frequency was low. Engagement of tozorakimab with endogenous IL-33 in serum and nasal airways was demonstrated. Tozorakimab significantly reduced serum IL-5 and IL-13 levels in patients with COPD compared with placebo. Overall, tozorakimab was well tolerated, with a linear, time-independent serum PK profile. Additionally, biomarker studies demonstrated proof of mechanism. Overall, these data support the further clinical development of tozorakimab in COPD and other inflammatory diseases.

In utero magnetic resonance imaging for diagnosis of dural venous sinus ectasia with thrombosis in the fetus.

BACKGROUND: Dural venous sinus ectasia with thrombosis (DVSET) in the fetus is a rare condition that can be diagnosed prenatally with the use of fetal MR imaging, yet with limited indication of long-term clinical significance. OBJECTIVE: To describe and evaluate the diagnostic value of fetal MR imaging in the prenatal diagnosis of dural venous sinus ectasia with thrombosis and its clinical significance. MATERIALS AND METHODS: We report a series of nine fetuses with dural venous sinus ectasia with thrombosis. The mothers, located in four feto-maternal centres, were referred for fetal MR imaging due to space occupying lesions identified on second-trimester antenatal ultrasound. RESULTS: In all but one case the dural venous sinus ectasia with thrombosis was in the vicinity of the venous confluence (VC) with various extension in the posterior dural sinuses. Antenatal follow-up imaging was performed in seven cases and showed progression in one, stable appearances in one and regression in five cases. Three pregnancies were terminated. In the remaining six cases there was no reported neurological deficit at up to 44 months of clinical follow-up. CONCLUSION: This is among the largest series of postnatal clinical follow-up in cases of prenatal diagnosis of dural venous sinus ectasia with thrombosis in the literature. Clinical follow-up suggests a good prognosis when antenatal follow-up shows partial or complete thrombus resolution.

Changes in coagulation factor activity and content of di(2-ethylhexyl)phthalate in frozen plasma units during refrigerated storage for up to five days after thawing.

BACKGROUND: Thawed plasma is typically transfused to supply coagulation factors but factor activity declines during refrigerated storage. Refrigerating thawed plasma for longer than 24 hours could reduce plasma wastage and make plasma more readily available for emergency transfusions. We measured coagulation factor activity and di(2-ethylhexyl)phthalate (DEHP) concentration in frozen plasma (FP) thawed and stored at 1 to 6°C for up to 5 days. STUDY DESIGN AND METHODS: FP units prepared using "top-and-bottom" collection sets were thawed, refrigerated, and sampled aseptically at 0, 24, 72, and 120 hours after thawing (n = 54). Clotting factor activities and prothrombin times (PTs) were measured using an automated coagulation factor analyzer. DEHP was measured by high-performance liquid chromatography after hexane extraction (n = 11). Unit sterility was confirmed using an automated microbial detection system. RESULTS: Factor (F)V and FVIII, but not FVII, declined significantly within 24 hours. By Day 5, mean losses were 20, 14, and 41%, in FV, FVII, and FVIII, respectively; fibrinogen activity did not change. PT values were prolonged by 9% on Day 5. Mean DEHP levels increased from 22 ppm at thaw to 66 ppm on Day 5. CONCLUSIONS: The bulk of coagulation factor activity losses during storage occurred in the first 24 hours. Coagulation factor activities remaining in FP after 5 days did not differ from those previously reported in similar products frozen within 24 hours of phlebotomy. While DEHP levels in 5-day-thawed FP are not of concern for adult patients, for infants, DEHP levels can be minimized by using FP refrigerated for no more than 24 hours.

Gestation-specific reference intervals for right and left ventricular ejection force from 12 to 40 weeks of gestation.

AIM: Ejection force of the fetal cardiac ventricles has previously been described from 18weeks of gestation. We aimed to establish gestation-specific reference intervals for ventricular ejection force (VEF) from 12 to 40weeks of pregnancy. MATERIAL AND METHODS: In a cross-sectional observational study of singleton pregnancies, examinations were performed in 236 women evenly distributed across each week of pregnancy from 12 to 40weeks. Each mother was scanned once. For the aortic and pulmonary valves, the time to peak velocity (TPV) and the average (TAV) and peak flow velocity in systole (PSV) was measured. For each we averaged values from three consecutive complexes. The outlet valve diameters were measured and the VEF on both the right and left sides were calculated using the formula VEF=(1.055×valve area×time to peak velocity×TAV)×(PSV/TPV) where 1.055 represents the density of blood. Measurements were repeated in 40 women to assess intraobserver reproducibility and in 19 women for interobserver variability. RESULTS: We present reference intervals for right and left VEF. We demonstrated that the ventricular force on both right and left sides increases with advancing gestational age. CONCLUSION: Fetal cardiac physiology can be studied and Doppler indices reliably measured as early as the late first trimester of pregnancy. Ventricular ejection force and its relationship with fetal growth could be explored in future studies and this may eventually provide better understanding of changes which may predispose to adult cardiac disease.