A road map for the management of a pregnancy complicated by maternal bladder exstrophy.

Bladder exstrophy (BE) is a congenital genito-urinary malformation where there is a defect in the abdominal wall resulting in a protruding open bladder with exposed mucosa (Resnik R.P. et al. Creasy and Resnik's maternal-fetal medicine: principles and practice. Elsevier, 2019). Several reconstructive procedures are required to correct the anomalies, resulting in an ileal conduit which is an alternate urinary reservoir reconstructed from the terminal ileum (Madersbacher S, et al. J Urol 169(3):985-90, 2003). We describe the care of a pregnant woman with BE and outline the principles of management of her pregnancy with a multidisciplinary team. Timely pre-operative planning is advised to minimise intraoperative complications in the event of a caesarean section. The woman went on to have an uncomplicated classical caesarean section at term by midline laparotomy with a good outcome for both mother and baby.

Late first-trimester ultrasound findings can alter management after high-risk NIPT result.

OBJECTIVE: To evaluate the impact of detailed late first-trimester ultrasound (LFTU) on the positive predictive value (PPV) of a high-risk non-invasive prenatal test (NIPT) result for various chromosomal abnormalities. METHODS: This was a retrospective study of all cases undergoing invasive prenatal testing from three tertiary providers of obstetric ultrasound over 4 years, each using NIPT as a first-line screening test. Data were collected from pre-NIPT ultrasound, NIPT, LFTU, placental serology and later ultrasound examinations. Prenatal testing for chromosomal abnormalities was performed by microarray, initially using array comparative genomic hybridization and then single nucleotide polymorphism (SNP) array for the last 2 years. Uniparental disomy testing was performed by SNP array during all 4 years. The majority of NIPT tests were analyzed using the Illumina platform, initially confined to the assessment of the common autosomal trisomies, sex chromosome aneuploidies and rare autosomal trisomies (RAT), then extending to genome-wide analysis for the last 2 years. RESULTS: Amniocentesis or chorionic villus sampling (CVS) was performed on 2657 patients, 1352 (51%) of whom had undergone prior NIPT, with 612 (45%) of these returning a high-risk result and meeting the inclusion criteria for the study. LFTU findings significantly affected the PPV of the NIPT result for trisomies 13 (T13), 18 (T18) and 21 (T21), monosomy X (MX) and RAT but not for the other sex chromosomal abnormalities or segmental imbalances (> 7 Mb). Abnormal LFTU increased the PPV close to 100% for T13, T18, T21, MX and RAT. The magnitude of the change in PPV was highest for the most severe chromosomal abnormalities. When LFTU was normal, the incidence of confined placental mosaicism (CPM) was highest in those with a high-risk NIPT result for T13, followed by T18 and T21. After normal LFTU, the PPV for T21, T18, T13 and MX decreased to 68%, 57%, 5% and 25%, respectively. CONCLUSIONS: LFTU after a high-risk NIPT result can alter the PPV for many chromosomal abnormalities, assisting counseling regarding invasive prenatal testing and pregnancy management. The high PPVs of NIPT for T21 and T18 are not sufficiently modified by normal LFTU findings to alter management. These at-risk patients should be offered CVS for earlier diagnosis, particularly given the low rate of CPM associated with these aneuploidies. Patients with a high-risk NIPT result for T13 and normal LFTU findings often wait for amniocentesis or avoid invasive testing altogether given the low PPV and higher rate of CPM in this context. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Influence of fibroids on cell-free DNA screening accuracy.

OBJECTIVE: Cell-free DNA (cfDNA) screening assesses both maternal and placental cfDNA. Fibroids are common and release cfDNA into maternal serum. Genetic abnormality is seen in 50% of fibroids. We aimed to assess the impact of fibroids on the accuracy of genome-wide cfDNA screening. METHODS: This was a prospective cohort study of singleton pregnancies examined at one of two centers in Melbourne and Sydney, Australia, between 1 November 2019 and 31 December 2020. All cases underwent pretest ultrasound examination to confirm an ongoing pregnancy of at least 10 weeks' gestation, and, at this stage, the number and volume of any uterine fibroid were documented. Genome-wide cfDNA screening was performed to detect all copy-number variants (CNV) > 7 megabases. The incidence of a false-positive result was compared between cases with and those without fibroids. RESULTS: Over the 14-month study period, 13 184 patients underwent cfDNA screening, of whom 1017 (7.7%) had fibroids. Fibroids were not identified in any of the 17 participants who had a false-positive result for chromosomes 13, 18, 21, X or Y. Ninety-five (0.7%) cases were screen-positive for subchromosomal aberration (SA), rare autosomal trisomy (RAT) or multiple abnormalities (MA), with 10 of these cases having a fetal genetic abnormality. The incidence of a false-positive RAT, MA or SA result was significantly higher in participants with fibroids (20/1017 (2.0%)) than in those without fibroids (64/12 167 (0.5%)). Women with fibroids were approximately six times as likely to have a false-positive result for SA, and this was associated positively with both fibroid number and volume. CONCLUSIONS: Most women with fibroids do not have an abnormal result on genome-wide cfDNA screening. However, CNVs due to fibroids are associated with false-positive SA findings, although fibroids do not appear to influence cfDNA screening accuracy for the common autosomal trisomies or sex-chromosomal abnormalities. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

IL4-10 fusion protein: a novel immunoregulatory drug combining activities of interleukin 4 and interleukin 10.

The objective of this study was to test the capacity of a newly developed fusion protein of interleukin 4 (IL-4) and IL-10 [IL4-10 fusion protein (FP)] to shift multiple pro-inflammatory pathways towards immune regulation, and to inhibit pro-inflammatory activity in arthritis models. The effects of IL4-10 FP in comparison with IL-4, IL-10 and IL-4 plus IL-10 on pro- and anti-inflammatory mediators, T cells and immunoglobulin (Ig) receptors in favour of immunoregulatory activity were studied. In addition, the capacity of IL4-10 FP to inhibit pro-inflammatory activity in ex-vivo and in-vivo arthritis models was investigated. IL4-10 FP robustly inhibited pro-inflammatory cytokine [IL-1ß, tumour necrosis factor (TNF)-α, IL-6 and IL-8] production in whole blood cultures, mediated by both the IL-10 and the IL-4 moiety. IL4-10 fusion protein induced IL-1 receptor antagonist (IL-1RA) production and preserved soluble TNF receptor (sTNFR) levels, strongly increasing IL-1RA/IL-1ß and sTNFR/TNF-α ratios. In addition, IL4-10 FP strongly inhibited T helper (Th) type 1 and 17 cytokine secretion, while maintaining FoxP3 expression and up-regulating Th2 activity. In addition, while largely leaving expression of activating Fc gamma receptor (FcγR)I, III and Fc epsilon receptor (FcεR) unaffected, it significantly shifted the FcγRIIa/FcγRIIb ratio in favour of the inhibitory FcγRIIb. Moreover, IL4-10 FP robustly inhibited secretion of pro-inflammatory cytokines by rheumatoid arthritis synovial tissue and suppressed experimental arthritis in mice, without inducing B cell hyperactivity. IL4-10 fusion protein is a novel drug, signalling cells to induce immunoregulatory activity that overcomes limitations of IL-4 and IL-10 stand-alone therapy, and therefore has therapeutic potential for inflammatory diseases such as rheumatoid arthritis.

Visual grading analysis of digital neonatal chest phantom X-ray images: Impact of detector type, dose and image processing on image quality.

OBJECTIVES: To evaluate the impact of digital detector, dose level and post-processing on neonatal chest phantom X-ray image quality (IQ). METHODS: A neonatal phantom was imaged using four different detectors: a CR powder phosphor (PIP), a CR needle phosphor (NIP) and two wireless CsI DR detectors (DXD and DRX). Five different dose levels were studied for each detector and two post-processing algorithms evaluated for each vendor. Three paediatric radiologists scored the images using European quality criteria plus additional questions on vascular lines, noise and disease simulation. Visual grading characteristics and ordinal regression statistics were used to evaluate the effect of detector type, post-processing and dose on VGA score (VGAS). RESULTS: No significant differences were found between the NIP, DXD and CRX detectors (p>0.05) whereas the PIP detector had significantly lower VGAS (p< 0.0001). Processing did not influence VGAS (p=0.819). Increasing dose resulted in significantly higher VGAS (p<0.0001). Visual grading analysis (VGA) identified a detector air kerma/image (DAK/image) of ~2.4 µGy as an ideal working point for NIP, DXD and DRX detectors. CONCLUSIONS: VGAS tracked IQ differences between detectors and dose levels but not image post-processing changes. VGA showed a DAK/image value above which perceived IQ did not improve, potentially useful for commissioning. KEY POINTS: • A VGA study detects IQ differences between detectors and dose levels. • The NIP detector matched the VGAS of the CsI DR detectors. • VGA data are useful in setting initial detector air kerma level. • Differences in NNPS were consistent with changes in VGAS.

Implications of failure to achieve a result from prenatal maternal serum cell-free DNA testing: a historical cohort study.

OBJECTIVE: To investigate the pregnancy outcomes in a cohort of women who failed to obtain a result in non-invasive prenatal testing (NIPT). DESIGN: Historical cohort study. SETTING: A multicentre private practice in Sydney, Australia. POPULATION: Women who failed to obtain a result from NIPT (n = 131). METHODS: The maternal characteristics, antenatal investigations and pregnancy outcomes for these women were compared with those who obtained a result at the same practice and to the general Australian obstetric population. MAIN OUTCOME MEASURES: Antenatal investigations: pregnancy-associated plasma protein-A (PAPP-A), free ß-human chorionic gonadotrophin (ß-hCG), placental growth factor (PlGF), uterine artery pulsatility index (PI), mean arterial pressure (MAP). Pregnancy outcomes: chromosomal abnormality, pre-eclampsia, gestational diabetes, small-for-gestational-age (SGA), preterm delivery. RESULTS: Only 1.1% of NIPT samples failed to return a result. This cohort was significantly older and had significantly increased weight compared with the general Australian obstetric population. Pregnancy outcomes were available for 94% of the cohort. There were significantly higher rates of chromosomal aneuploidies (6.5% versus 0.2%, P < 0.0001), pre-eclampsia (11% versus 1.5%, P < 0.0001) and gestational diabetes (23% versus 7.5%, P < 0.0001) compared with the general obstetric population. Rates of preterm delivery and SGA were elevated but did not reach significance. Antenatal investigations demonstrated decreased PAPP-A MoM (0.75 versus 1.14, P < 0.0001), decreased free ß-hCG (0.71 versus 1.01, P < 0.0001) and increased uterine artery PI (1.79 versus 1.65, P = 0.02). CONCLUSION: Women who fail to obtain a result from NIPT are at increased risk of adverse pregnancy outcomes, in particular chromosomal aneuploidy, gestational diabetes and pre-eclampsia. FUNDING: None received. TWEETABLE ABSTRACT: Women who fail to obtain a result from cell-free DNA NIPT are at increased risk of adverse pregnancy outcomes.

Sex steroids in relation to cardiac structure and function in men.

The prevalence of testosterone substitution as well as of androgen deprivation therapy in men is increasing. This review aims to summarise available knowledge of the effects of sex steroids on cardiac structure and function in men. MEDLINE was searched through PubMed. Original studies, systematic reviews and meta-analyses, and relevant citations were screened. A short-term hormonal intervention study in healthy young men with respect to echocardiographic parameters of structure and function was performed. Preclinical research provides sufficient evidence for the heart as a substrate for sex hormones. In animals, administration of oestradiol appears to have beneficial effects on cardiac structure and function, whereas administration of testosterone to noncastrated animals adversely affects cardiac function. However, the effects of sex steroids on cardiac function and structure appear more heterogeneous in human observational studies while comparative, prospective studies in humans are lacking. It is concluded that although effects of testosterone substitution as well as of androgen deprivation on cardiac structure and function can be expected based on pre-clinical research, there exists an important knowledge gap of the effects of hormonal intervention in men. As such, there is a need to address this question in future prospective intervention trials.

γ-H2AX foci as in vivo effect biomarker in children emphasize the importance to minimize x-ray doses in paediatric CT imaging.

OBJECTIVES: Investigation of DNA damage induced by CT x-rays in paediatric patients versus patient dose in a multicentre setting. METHODS: From 51 paediatric patients (median age, 3.8 years) who underwent an abdomen or chest CT examination in one of the five participating radiology departments, blood samples were taken before and shortly after the examination. DNA damage was estimated by scoring γ-H2AX foci in peripheral blood T lymphocytes. Patient-specific organ and tissue doses were calculated with a validated Monte Carlo program. Individual lifetime attributable risks (LAR) for cancer incidence and mortality were estimated according to the BEIR VII risk models. RESULTS: Despite the low CT doses, a median increase of 0.13 γ-H2AX foci/cell was observed. Plotting the induced γ-H2AX foci versus blood dose indicated a low-dose hypersensitivity, supported also by an in vitro dose-response study. Differences in dose levels between radiology centres were reflected in differences in DNA damage. LAR of cancer mortality for the paediatric chest CT and abdomen CT cohort was 0.08 and 0.13 ‰ respectively. CONCLUSION: CT x-rays induce DNA damage in paediatric patients even at low doses and the level of DNA damage is reduced by application of more effective CT dose reduction techniques and paediatric protocols. .

Are serum HE4 or ROMA scores useful to experienced examiners for improving characterization of adnexal masses after transvaginal ultrasonography?

OBJECTIVE: To determine whether serum human-epididymis protein-4 (HE4) levels or Risk of Ovarian Malignancy Algorithm (ROMA) scores are useful second-stage tests for tumors thought to be difficult to characterize as benign or malignant on the basis of ultrasound findings by experienced examiners, and to investigate whether adding information on serum HE4 levels or ROMA scores to ultrasound findings improves diagnostic performance. METHODS: This was a prospective cross-sectional diagnostic accuracy study conducted in a tertiary referral center that enrolled consecutive women with a known adnexal mass scheduled for surgery. Experienced level III examiners classified each mass as certainly or probably benign, difficult to classify, or probably or certainly malignant after preoperative ultrasound examination. Serum HE4 and CA 125 levels were measured before surgery. RESULTS: The final database comprised 360 women, of whom 216 (60%) had benign and 144 (40%) had malignant disease. Examiners were highly confident in 196 cases (54%), moderately confident in 135 (38%) and completely uncertain about their diagnosis in 29 (8%) cases. With a sensitivity of 67% and specificity of 70%, subjective assessment outperformed HE4 and ROMA in the subgroup of difficult tumors. Both tests had low discriminatory capacity with poor areas under the receiver-operating characteristics curve of 0.536 (95% CI, 0.302-0.771) and 0.565 (95% CI, 0.294-0.836), respectively. A strategy that incorporates sequential testing of serum HE4 or ROMA scores after transvaginal ultrasonography resulted in a deterioration in overall test performance. CONCLUSION: Measurement of serum HE4 or calculating scores using the ROMA as secondary tests does not seem useful for classifying adnexal tumors after subjective assessment with transvaginal ultrasonography.

Uveitis Patterns and Severity: An Epidemiologic Study from a Tertiary Care Private Referral Center in Buenos Aires, Argentina.

PURPOSE: To report uveitis' spectrum in a private practice cohort in the city of Buenos Aires, Argentina. METHODS: Retrospective review at Instituto de la Visión (November 2011-October 2015). Standard demographics, ethnicity and Native American aboriginal ancestry were recorded. RESULTS: Among 212 patients, median age 45 (6-97), 10% pediatric, 35% bilateral, 72% non-idiopathic, 36% infectious. Anterior uveitis presented in 50%, followed by posterior (32%), intermediate (9%) and panuveitis (8%). Frequent visits (≥ 6 per year) needed by 29%: posterior, non-idiopathic disease with 79% systemic immunosuppression requirement was their main presentation. Native American aboriginal ancestry was reported by 22.64% of the whole cohort and 37% of frequent visits' subgroup. CONCLUSIONS: Unilateral, non-idiopathic, non-infectious anterior uveitis was the most frequent presentation, in agreement with reports coming from western developed cities. The multi-racial Argentinian population with specific Native American aboriginal ancestry might contribute to certain forms of posterior uveitis and their response to treatment.

Seven general radiography x-ray detectors with pixel sizes ranging from 175 to 76µm: technical evaluation with the focus on orthopaedic imaging.

Aim. Flat panel detectors with small pixel sizes general can potentially improve imaging performance in radiography applications requiring fine detail resolution. This study evaluated the imaging performance of seven detectors, covering a wide range of pixel sizes, in the frame of orthopaedic applications.Material and methods. Pixel sizes ranged from 175 (detector A175) to 76µm (detector G76). Modulation transfer function (MTF) and detective quantum efficiency (DQE) were measured using International Electrotechnical Commission (IEC) RQA3 beam quality. Threshold contrast (CT) and a detectability index (d') were measured at three air kerma/image levels. Rabbit shoulder images acquired at 60 kV, over five air kerma levels, were evaluated in a visual grading study for anatomical sharpness, image noise and overall diagnostic image quality by four radiologists. The detectors were compared to detector E124.Results. The 10% point of the MTF ranged from 3.21 to 4.80 mm-1, in going from detector A175to detector G76. DQE(0.5 mm-1) measured at 2.38µGy/image was 0.50 ± 0.05 for six detectors, but was higher for F100at 0.62. High frequency DQE was superior for the smaller pixel detectors, howeverCTfor 0.25 mm discs correlated best with DQE(0.5 mm-1). Correlation betweenCTand the detectability model was good (R2= 0.964).CTfor 0.25 mm diameter discs was significantly higher for D150and F100compared to E124. The visual grading data revealed higher image quality ratings for detectors D125and F100compared to E124. An increase in air kerma was associated with improved perceived sharpness and overall quality score, independent of detector. Detectors B150, D125, F100and G76, performed well in specific tests, however only F100consistently outperformed the reference detector.Conclusion. Pixel size alone was not a reliable predictor of small detail detectability or even perceived sharpness in a visual grading analysis study.

Simultaneous T1 measurements and proton resonance frequency shift based thermometry using variable flip angles.

A method is presented which allows precise temperature and longitudinal (T(1)) relaxation time measurements with high spatial and temporal resolution. This is achieved by combining dynamic variable flip angle based T(1) relaxation mapping with proton resonance frequency shift based thermometry. Herein, dynamic T(1) mapping is either used as a complementary measure of temperature or for the detection of T(1) contrast agent release. For the first application, the temperature evolution during a high-intensity focused ultrasound tissue ablation experiment was measured in both, porcine fat and muscle, simultaneously. In this application, temperature accuracies of 2.5 K for T(1)-based thermometry in fat and 1.2 K for proton resonance frequency shift-based thermometry in muscle were observed. The second application relates to MR-guidance of high-intensity focused ultrasound-induced local drug delivery by means of thermo-sensitive liposomes labeled with a T(1) contrast agent (Gd-HPDO3A). When the measured temperature exceeded the phase transition temperature of the liposomes, T(1) was observed to decrease with a good temporal and spatial correlation due to the release of Gd-HPDO3A. The presented results demonstrate the feasibility of the proposed method for two important applications in MR-guided noninvasive therapy. It offers a high temporal resolution when compared with interleaved Look-Locker based T(1) mapping techniques and thus represents an interesting candidate for simultaneous real-time monitoring of T(1) and temperature changes.

An unexpected cause of constipation and abdominal distension in COPD.

Question: A 62-year old man presented to our tertiary care hospital for a second opinion regarding end stage COPD GOLD 4D. He had a medical history of former alcohol use complicated by liver steatosis and former smoking. Upon admission the patient complained of constipation and abdominal distension. Physical examination showed diffuse hypertympanic percussion and diffuse abdominal pain upon palpation without signs of peritoneal irrita- tion. CRP, hemoglobin, lactate, liver enzymes, and serum creatinine were within limits of normal. Abdominal radiography showed dilatation of the colon transversum with intramural and intra-abdominal free air (Figure 1). Contrast-enhanced abdominal CT showed extensive intramural air in the right hemicolon (Figure 2). Answer: The findings are consistent with pneumatosis intestinalis (PI). Conservative management with oxygen, triple bronchodilator therapy, fasting, laxation and antibiotic therapy resulted in resolution of the clinical symptoms.

SARS-CoV-2-related Multisystem Inflammatory Syndrome in Adult complicated by myocarditis and cardiogenic shock.

Multisystem Inflammatory Syndrome in Adult (MIS-A) is a rare COVID-19 complication, presenting as fever with laboratory evidence of inflammation, severe illness requiring hospitalization and multisystem organ involvement. We report on a 25-year-old man presenting with fever, rash, abdominal pain, diarrhoea and vomiting following prior asymptomatic COVID-19 infection. He developed refractory shock and type 1 respiratory insufficiency requiring mechanical ventilation. Diagnostic testing revealed significant inflammation, anemia, thrombocytopenia, acute kidney injury, hepatosplenomegaly, colitis, lymphadenopathy and myocarditis necessitating inotropy. Ventilatory, vasopressor and inotropic support was weaned following pulse corticosteroids and intravenous immunoglobulins. Heart failure therapy was started. Short-term follow-up shows resolution of inflammation and cardiac dysfunction.

ESTRO-ACROP guideline on surface guided radiation therapy.

Surface guidance systems enable patient positioning and motion monitoring without using ionising radiation. Surface Guided Radiation Therapy (SGRT) has therefore been widely adopted in radiation therapy in recent years, but guidelines on workflows and specific quality assurance (QA) are lacking. This ESTRO-ACROP guideline aims to give recommendations concerning SGRT roles and responsibilities and highlights common challenges and potential errors. Comprehensive guidelines for procurement, acceptance, commissioning, and QA of SGRT systems installed on computed tomography (CT) simulators, C-arm linacs, closed-bore linacs, and particle therapy treatment systems are presented that will help move to a consensus among SGRT users and facilitate a safe and efficient implementation and clinical application of SGRT.

Are intravitreal injections essential during the COVID-19 pandemic? Global preferred practice patterns and practical recommendations.

Tertiary outpatient ophthalmology clinics are high-risk environments for COVID-19 transmission, especially retina clinics, where regular follow-up is needed for elderly patients with multiple comorbidities. Intravitreal injection therapy (IVT) for chronic macular diseases, is one of the most common procedures performed, associated with a significant burden of care because of the vigorous treatment regimen associated with multiple investigations. While minimizing the risk of COVID-19 infection transmission is a priority, this must be balanced against the continued provision of sight-saving ophthalmic care to patients at risk of permanent vision loss. This review aims to give evidence-based guidelines on managing IVT during the COVID-19 pandemic in common macular diseases such as age-related macular degeneration, diabetic macula edema and retinal vascular disease and to report on how the COVID-19 pandemic has affected IVT practices worldwide.To illustrate some real-world examples, 18 participants in the International Retina Collaborative, from 15 countries and across four continents, were surveyed regarding pre- and during- COVID-19 pandemic IVT practices in tertiary ophthalmic centers. The majority of centers reported a reduction in the number of appointments to reduce the risk of the spread of COVID-19 with varying changes to their IVT regimen to treat various macula diseases. Due to the constantly evolving nature of the COVID-19 pandemic, and the uncertainty about the normal resumption of health services, we suggest that new solutions for eye healthcare provision, like telemedicine, may be adopted in the future when we consider new long-term adaptations required to cope with the COVID-19 pandemic.

Intestinal barrier function in patients undergoing colectomy.

AIM: The aim of this pilot study was to determine whether the type of approach (open or laparoscopic) and the order of devascularization during laparoscopic colectomy affect intestinal barrier function, local inflammatory response and clinical outcome. METHOD: Twenty-two patients undergoing elective colectomy from April 2006 to July 2008 were randomized to two sequences of vascular ligation, starting with either the inferior mesenteric artery or the ileocolic artery. Eighteen patients scheduled for open surgery served as a prospective control group. To assess the intestinal barrier function, release of intestinal fatty-acid binding protein (I-FABP; a marker of mucosal injury and ischaemia) was measured pre- and postoperatively. Mesenteric lymph nodes were harvested to assess the expression of inflammatory mediator-related genes using multiplex ligation probe amplification. The study was registered under NTR1025. RESULTS: Laparoscopic devascularization starting at the ileocolic artery resulted in a significantly increased excretion of I-FABP over time (P = 0.002). In this group, the I-FABP levels were significantly increased on postoperative days 1 and 3 compared with preoperative values (P = 0.011 and P = 0.001, respectively). There were no differences in expression of inflammatory mediator-related genes or postoperative morbidity among the groups. CONCLUSIONS: In this pilot study, devascularization commencing at the ileocolic artery during laparoscopic colectomy was associated with prolonged intestinal mucosal ischaemia.