Acute fetal cardiovascular adaptation to artificial placenta in sheep model.

OBJECTIVE: To describe the acute cardiovascular adaptation of the fetus after connection to an artificial placenta (AP) in a sheep model, using ultrasound and invasive and non-invasive hemodynamic assessment. METHODS: This was an experimental study of 12 fetal sheep that were transferred to an AP system, consisting of a pumpless circuit with umbilical cord connection, at 109-117 days' gestation. The study was designed to collect in-utero and postcannulation measurements in all the animals. The first six consecutive fetuses were fitted with intravascular catheters and perivascular probes to obtain invasive physiological data, including arterial and venous intravascular pressures and perivascular blood flows, with measurements taken in utero and at 5 and 30 min after cannulation. These experiments were designed with a survival goal of 1-3 h. The second set of six fetuses were not fitted with catheters, and experiments were aimed at 3-24 h of survival. Echocardiographic assessment of cardiac anatomy and function, as well as measurements of blood flow and pre- and postmembrane pressures recorded by circuit sensors in the AP system, were available for most of the fetuses. These data were acquired in utero and at 30 and 180 min after cannulation. RESULTS: Compared with in-utero conditions, the pulsatility index at 30 and 180 min after connection to the AP system was reduced in the umbilical artery (median, 1.36 (interquartile range (IQR), 1.06-1.50) vs 0.38 (IQR, 0.31-0.50) vs 0.36 (IQR, 0.29-0.41); P < 0.001 for extreme timepoints) and the ductus venosus (median, 0.50 (IQR, 0.41-0.67) vs 0.29 (IQR, 0.22-0.33) vs 0.36 (IQR, 0.22-0.41); P = 0.011 for extreme timepoints), whereas umbilical venous peak velocity increased (median, 20 cm/s (IQR, 18-22 cm/s) vs 39 cm/s (IQR, 31-43 cm/s) vs 43 cm/s (IQR, 34-54 cm/s); P < 0.001 for extreme timepoints) and flow became more pulsatile. Intravascular monitoring showed that arterial and venous pressures increased transiently after connection, with median values for mean arterial pressure at baseline, 5 min and 30 min of 43 mmHg (IQR, 35-54 mmHg), 72 mmHg (IQR, 61-77 mmHg) and 58 mmHg (IQR, 50-64 mmHg), respectively (P = 0.02 for baseline vs 5 min). Echocardiography showed a similar transient elevation of fetal heart rate at 30 and 180 min after connection compared with in utero (median, 145 bpm (IQR, 142-156 bpm) vs 188 bpm (IQR, 171-209 bpm) vs 175 bpm (IQR, 165-190 bpm); P = 0.001 for extreme timepoints). Fetal cardiac structure and function were mainly preserved; median values for right fractional area change were 36% (IQR, 34-41%) in utero, 38% (IQR, 30-40%) at 30 min and 37% (IQR, 33-40%) at 180 min (P = 0.807 for extreme timepoints). CONCLUSIONS: Connection to an AP system resulted in a transient fetal hemodynamic response that tended to normalize over hours. In this short-term evaluation, cardiac structure and function were preserved. However, the system resulted in non-physiologically elevated venous pressure and pulsatile flow, which should be corrected to avoid later impairment of cardiac function. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Corpus callosum size by neurosonography in fetuses with congenital heart defect and relationship with expected pattern of brain oxygen supply.

OBJECTIVE: To evaluate corpus callosum (CC) size by neurosonography (NSG) in fetuses with an isolated major congenital heart defect (CHD) and explore the association of CC size with the expected pattern of in-utero oxygen supply to the brain. METHODS: A total of 56 fetuses with postnatally confirmed isolated major CHD and 56 gestational-age-matched controls were included. Fetuses with CHD were stratified into two categories according to the main expected pattern of cerebral arterial oxygen supply: Class A, moderately to severely reduced oxygen supply (left outflow tract obstruction and transposition of the great arteries) and Class B, near normal or mildly impaired oxygenated blood supply to the brain (other CHD). Transvaginal NSG was performed at 32-36 weeks in all fetuses to evaluate CC length, CC total area and areas of CC subdivisions in the midsagittal plane. RESULTS: CHD fetuses had a significantly smaller CC area as compared to controls (7.91 ± 1.30 vs 9.01 ± 1.44 mm2 ; P < 0.001), which was more pronounced in the most posterior part of the CC. There was a significant linear trend for reduced CC total area across the three clinical groups, with CHD Class-A cases showing more prominent changes (controls, 9.01 ± 1.44 vs CHD Class B, 8.18 ± 1.21 vs CHD Class A, 7.53 ± 1.33 mm2 ; P < 0.05). CONCLUSIONS: Fetuses with major CHD had a smaller CC compared with controls, and the difference was more marked in the CHD subgroup with expected poorer brain oxygenation. Sonographic CC size could be a clinically feasible marker of abnormal white matter development in CHD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

FDG PET-CT imaging of therapeutic response in granulomatous lymphocytic interstitial lung disease (GLILD) in common variable immunodeficiency (CVID).

Common variable immunodeficiency (CVID) is the most common severe adult primary immunodeficiency and is characterized by a failure to produce antibodies leading to recurrent predominantly sinopulmonary infections. Improvements in the prevention and treatment of infection with immunoglobulin replacement and antibiotics have resulted in malignancy, autoimmune, inflammatory and lymphoproliferative disorders emerging as major clinical challenges in the management of patients who have CVID. In a proportion of CVID patients, inflammation manifests as granulomas that frequently involve the lungs, lymph nodes, spleen and liver and may affect almost any organ. Granulomatous lymphocytic interstitial lung disease (GLILD) is associated with a worse outcome. Its underlying pathogenic mechanisms are poorly understood and there is limited evidence to inform how best to monitor, treat or select patients to treat. We describe the use of combined 2-[(18)F]-fluoro-2-deoxy-d-glucose positron emission tomography and computed tomography (FDG PET-CT) scanning for the assessment and monitoring of response to treatment in a patient with GLILD. This enabled a synergistic combination of functional and anatomical imaging in GLILD and demonstrated a widespread and high level of metabolic activity in the lungs and lymph nodes. Following treatment with rituximab and mycophenolate there was almost complete resolution of the previously identified high metabolic activity alongside significant normalization in lymph node size and lung architecture. The results support the view that GLILD represents one facet of a multi-systemic metabolically highly active lymphoproliferative disorder and suggests potential utility of this imaging modality in this subset of patients with CVID.

Facilitated subcutaneous immunoglobulin (fSCIg) therapy--practical considerations.

There is an increasing range of therapeutic options for primary antibody-deficient patients who require replacement immunoglobulin. These include intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), rapid push SCIg and most recently recombinant human hyaluronidase-facilitated SCIg (fSCIg). Advantages of fSCIg include fewer needle punctures, longer infusion intervals and an improved adverse effect profile relative to IVIg. Limited real-life experience exists concerning the practical aspects of switching or starting patients on fSCIg. We describe the first 14 patients who have been treated with fSCIg at the Immunodeficiency Centre for Wales (ICW), representing more than 6 patient-years of experience. The regimen was well tolerated, with high levels of satisfaction and no increase in training requirement, including for a treatment-naive patient. Two patients discontinued fSCIg due to pain and swelling at the infusion site, and one paused therapy following post-infusion migraines. Ultrasound imaging of paired conventional and facilitated SCIg demonstrated clear differences in subcutaneous space distribution associated with a 10-fold increase in rate and volume delivery with fSCIg. Patient profiles for those choosing fSCIg fell into two main categories: those experiencing clinical problems with their current treatment and those seeking greater convenience and flexibility. When introducing fSCIg, consideration of the type and programming of infusion pump, needle gauge and length, infusion site, up-dosing schedule, home training and patient information are important, as these may differ from conventional SCIg. This paper provides guidance on practical aspects of the administration, training and outcomes to help inform decision-making for this new treatment modality.

Quantitative ultrasound texture analysis of fetal lungs to predict neonatal respiratory morbidity.

OBJECTIVE: To develop and evaluate the performance of a novel method for predicting neonatal respiratory morbidity based on quantitative analysis of the fetal lung by ultrasound. METHODS: More than 13,000 non-clinical images and 900 fetal lung images were used to develop a computerized method based on texture analysis and machine learning algorithms, trained to predict neonatal respiratory morbidity risk on fetal lung ultrasound images. The method, termed 'quantitative ultrasound fetal lung maturity analysis' (quantusFLM™), was then validated blindly in 144 neonates, delivered at 28 + 0 to 39 + 0 weeks' gestation. Lung ultrasound images in DICOM format were obtained within 48 h of delivery and the ability of the software to predict neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, was determined. RESULTS: Mean (SD) gestational age at delivery was 36 + 1 (3 + 3) weeks. Among the 144 neonates, there were 29 (20.1%) cases of neonatal respiratory morbidity. Quantitative texture analysis predicted neonatal respiratory morbidity with a sensitivity, specificity, positive predictive value and negative predictive value of 86.2%, 87.0%, 62.5% and 96.2%, respectively. CONCLUSIONS: Quantitative ultrasound fetal lung maturity analysis predicted neonatal respiratory morbidity with an accuracy comparable to that of current tests using amniotic fluid.

A UK national audit of hereditary and acquired angioedema.

Hereditary angioedema (HAE) and acquired angioedema (AAE) are rare life-threatening conditions caused by deficiency of C1 inhibitor (C1INH). Both are characterized by recurrent unpredictable episodes of mucosal swelling involving three main areas: the skin, gastrointestinal tract and larynx. Swelling in the gastrointestinal tract results in abdominal pain and vomiting, while swelling in the larynx may be fatal. There are limited UK data on these patients to help improve practice and understand more clearly the burden of disease. An audit tool was designed, informed by the published UK consensus document and clinical practice, and sent to clinicians involved in the care of HAE patients through a number of national organizations. Data sets on 376 patients were received from 14 centres in England, Scotland and Wales. There were 55 deaths from HAE in 33 families, emphasizing the potentially lethal nature of this disease. These data also show that there is a significant diagnostic delay of on average 10 years for type I HAE, 18 years for type II HAE and 5 years for AAE. For HAE the average annual frequency of swellings per patient affecting the periphery was eight, abdomen 5 and airway 0·5, with wide individual variation. The impact on quality of life was rated as moderate or severe by 37% of adult patients. The audit has helped to define the burden of disease in the UK and has aided planning new treatments for UK patients.

Fetal brain MRI texture analysis identifies different microstructural patterns in adequate and small for gestational age fetuses at term.

OBJECTIVES: We tested the hypothesis whether a texture analysis (TA) algorithm applied to MRI brain images identified different patterns in small for gestational age (SGA) fetuses as compared with adequate for gestational age (AGA). STUDY DESIGN: MRI was performed on 83 SGA and 70 AGA at 37 weeks' GA. Texture features were quantified in the frontal lobe, basal ganglia, mesencephalon, cerebellum and cingulum. A classification algorithm based on discriminative models was used to correlate texture features with clinical diagnosis. RESULTS: Region of interest delineation in all areas was achieved in 61 SGA (12 vasodilated) and 52 AGA; this was the sample for TA feature extraction which allowed classifying SGA from AGA with accuracies ranging from 90.9 to 98.9% in SGA versus AGA comparison and from 93.6 to 100% in vasodilated SGA versus AGA comparison. CONCLUSIONS: This study demonstrates that TA can detect brain differences in SGA fetuses. This supports the existence of brain microstructural changes in SGA fetuses.

Survey of clinical allergy services provided by clinical immunologists in the UK.

BACKGROUND: The UK National Health Service is failing to meet the need for diagnosis and treatment of allergic disorders, which are common and increasing in prevalence. The House of Commons select committee report on allergy services highlighted the inequalities and urgent need for investment. AIM: To survey the allergy workload provided by clinical immunologists to inform service planning and resource allocation. METHODS: The allergy services performed by clinical immunologists during a 12 month period from 1 April 2003 to 31 March 2004 were surveyed by means of a questionnaire via supra-regional audit groups. RESULTS: The immunology centres surveyed serve 32 million people and offer almost the complete repertoire of a specialised allergy service. There were large variations in clinic capacity, new referrals, appointment duration, and service configuration. Services were largely consultant delivered, but availability of joint clinics with paediatricians and anaesthetists was locally variable. Novel service delivery models utilising nurses and clinical assistants have been developed and merit further investigation. CONCLUSION: Consultant immunologists and trainees currently make a major contribution to the development and provision of specialised allergy services. Consultant immunologists will probably remain key providers of tertiary level allergy care in the UK in the long term (in line with other countries) and will be pivotal in supporting and developing the provision of equitable national access to specialist allergy services in a timely manner. Rapid progress in developing the new specialty of allergy and securing better access to services for patients in the short term will be best served by strengthening the collaborative relationship between allergists and clinical immunologists.

Transmission dynamics of Cryptosporidium in primates and herbivores at the Barcelona zoo: a long-term study.

Factors influencing the transmission of Cryptosporidium in primates and herbivores housed at the Barcelona zoo have been analyzed. The relationship between continuous and discontinuous oocyst shedding, both animal housing conditions and abiotic factors (seasonality, humidity, temperature) was examined to explain the epizootiology of the protozoan. Thirty six fecal samples from each of 11 primates (Pongidae, Cebidae, Cercopithecidae and Lemuridae) and 22 herbivores (Elephantidae, Camelidae, Cervidae, Giraffidae and Bovidae) were examined over the period of 1 year. The parasite transmission was based on the chronic infection status of some animals serving as a source of successive reinfection for other animals. The environmental temperature and humidity (seasonality), the physical features of the facilities, the vicinity of the animals and the physiological status induced by captivity contributed to transmission. The long-term character of this study was essential for obtaining these results and interpreting the complex relationships.