Analytical and experimental characterization of a miniature calorimetric sensor in pulsatile flow

The behaviour of a miniature calorimetric sensor, which is under consideration for catheter-based coronary artery flow assessment, is investigated in both steady and pulsatile tube flow. The sensor is composed of a heating element operated at constant power, and two thermopiles that measure flow-induced temperature differences over the sensor surface. An analytical sensor model is developed, which includes axial heat conduction in the fluid and a simple representation of the solid wall, assuming a quasi-steady sensor response to the pulsatile flow. To reduce the mathematical problem, described by a two-dimensional advection-diffusion equation, a spectral method is applied. A Fourier transform is then used to solve the resulting set of ordinary differential equations and an analytical expression for the fluid temperature is found. To validate the analytical model, experiments with the sensor mounted in a tube have been performed in steady and pulsatile water flow with various amplitudes and Strouhal numbers. Experimental results are generally in good agreement with theory and show a quasi-steady sensor response in the coronary flow regime. The model can therefore be used to optimize the sensor design for coronary flow assessment

Long-Term Outcomes of Standard Endovascular Aneurysm Repair in Patients With Severe Neck Angulation

Objective: Severe neck angulation is associated with complications after endovascular aneurysm repair (EVAR). Newer endografts may overcome this limitation, but the literature lacks long-term results. We studied the long-term outcomes of EVAR in patients with severe neck angulation. Methods: A retrospective case-control study of a prospective multicenter database was performed. All measurements were made with dedicated software with center lumen line reconstruction. A study group including patients with neck length >15 mm, infrarenal angle (β) >75 degrees or suprarenal angle (α) >60 degrees, and neck length 10 to 15 mm with β >60 degrees or α >45 degrees was compared with a control group matched for demographics and other morphologic neck features. The primary end point was type IA endoleak (EL1A). Secondary end points were freedom from neck-related secondary interventions, primary clinical success, and overall survival. Results: Forty-five patients were included in the angulated neck group and compared with 65 matched patients. Median follow-up was 7.4 years (interquartile range, 4.8-8.5 years). In the angulated neck group, mean α was 51.4 degrees (±21.1 degrees) and the mean β was 80.8 degrees (±15.6 degrees); in the nonangulated group, these were 17.9 degrees (±17.0 degrees) and 35.4 degrees (±20.0 degrees), respectively. At 7 years, five patients in the angulated neck group and two nonangulated patients developed EL1A, yielding a freedom from EL1A of 86.1% (n = 14; standard error [SE], 0.069) and 96.6% (n = 34; SE, 0.023), respectively (P = .056). After exclusion of a patient who developed an EL1A secondary to an endograft infection, this difference was significant: 86.1% (n = 14; SE, 0.069) in the angulated neck group and 98.2% (n = 34; SE, 0.018) in the nonangulated group (P = .016). At 7 years, freedom from neck-related secondary interventions was 91.7% (n = 14; SE, 0.059) and 91.6% (n = 29; SE, 0.029), respectively. The 7-year primary clinical success estimates were 41.2% (n = 11; SE, 0.085) and 56.6% (n = 20; SE, 0.072) for the angulated neck and nonangulated groups, respectively (P = .12). The 7-year survival rates were 44.3% (n = 18; SE, 0.076) vs 66.7% (n = 42; SE, 0.059) for the angulated neck and nonangulated groups, respectively (P = .25). Device integrity failure was not observed. Conclusions: Despite satisfactory results early and in the midterm, a higher rate of EL1A was identified among patients with severely angulated necks in the long term. However, mortality was not affected by this difference. These findings suggest that EVAR should be used judiciously in patients with extreme angulation of the proximal neck and highlight the need for close follow-up of EVAR, especially in the long term and in patients treated outside instructions for use.info:eu-repo/semantics/publishedVersio

Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis

OBJECTIVE: Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. DESIGN: In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. RESULTS: In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis ≥1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), ≥1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). CONCLUSION: The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias

Substantial and sustained improvement of serrated polyp detection after a simple educational intervention: Results from a prospective controlled trial

Objective: Serrated polyps (SPs) are an important cause of postcolonoscopy colorectal cancers (PCCRCs), which is likely the result of suboptimal SP detection during colonoscopy. We assessed the long-term effect of a simple educational intervention focusing on optimising SP detection. Design: An educational intervention, consisting of two 45 min training sessions (held 3 years apart) on serrated polyp detection, was given to endoscopists from 9 Dutch hospitals. Hundred randomly selected and untrained endoscopists from other hospitals were selected as control group. Our primary outcome measure was the proximal SP detection rate (PSPDR) in trained versus untrained endoscopists who participated in our faecal immunochemical test (FIT)-based population screening programme. Results: Seventeen trained and 100 untrained endoscopists were included, who performed 11 305 and 51 039 colonoscopies, respectively. At baseline, PSPDR was equal between the groups (9.3% vs 9.3%). After training, the PSPDR of trained endoscopists gradually increased to 15.6% in 2018. This was significantly higher than the PSPDR of untrained endoscopists, which remained stable around 10% (p=0.018). All below-average (ie, PSPDR ≤6%) endoscopists at baseline improved their PSPDR after training session 1, as did 57% of endoscopists with average PSPDR (6%-12%) at baseline. The second training session further improved the PSPDR in 44% of endoscopists with average PSPDR after the first training. Conclusion: A simple educational intervention was associated with substantial long-term improvement of PSPDR in a prospective controlled trial within FIT-based population screening. Widespread implementation of such interventions might be an easy way to improve SP detection, which may ultimately result in fewer PCCRCs. Trial registration number: NCT03902899

GATA transcription factors in testicular adrenal rest tumours

Testicular adrenal rest tumours (TARTs) are benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia. Recently, GATA transcription factors have been linked to the development of TARTs in mice. The aim of our study was to determine GATA expression in human TARTs and other steroidogenic tissues. We determined GATA expression in TARTs (n = 16), Leydig cell tumours (LCTs; n = 7), adrenal (foetal (n = 6) + adult (n = 10)) and testis (foetal (n = 13) + adult (n = 8)). We found testis-like GATA4, and adrenal-like GATA3 and GATA6 gene expressions by qPCR in human TARTs, indicating mixed testicular and adrenal characteristics of TARTs. Currently, no marker is available to discriminate TARTs from LCTs, leading to misdiagnosis and incorrect treatment. GATA3 and GATA6 mRNAs exhibited excellent discriminative power (area under the curve of 0.908 and 0.816, respectively), while immunohistochemistry did not. GATA genes contain several CREB-binding sites and incubation with 0.1 mM dibutyryl cAMP for 4 h stimulated GATA3, GATA4 and GATA6 expressions in a human foetal testis cell line (hs181.tes). Incubation of adrenocortical cells (H295RA) with ACTH, however, did not induce GATA expression in vitro Although ACTH did not dysregulate GATA expression in the only human ACTH-sensitive in vitro model available, our results do suggest that aberrant expression of GATA transcription factors in human TARTs might be involved in TART formation

Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: A multicentre cohort analysis

Objective Serrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC risk. We aimed to assess risk factors for CRC in a large cohort of patients with SPS and to evaluate the risk of CRC during surveillance. Design In this retrospective cohort analysis, all patients with SPS from seven centres in the Netherlands and two in the UK were enrolled. WHO criteria were used to diagnose SPS. Patients who only fulfilled WHO criterion-2, with IBD and/or a known hereditary CRC syndrome were excluded. Results In total, 434 patients with SPS were included for analysis; 127 (29.3%) were diagnosed with CRC. In a per-patient analysis =1 serrated polyp (SP) with dysplasia (OR 2.07; 95% CI 1.28 to 3.33), =1 advanced adenoma (OR 2.30; 95% CI 1.47 to 3.67) and the fulfilment of both WHO criteria 1 and 3 (OR 1.60; 95% CI 1.04 to 2.51) were associated with CRC, while a history of smoking was inversely associated with CRC (OR 0.36; 95% CI 0.23 to 0.56). Overall, 260 patients underwent surveillance after clearing of all relevant lesions, during which two patients were diagnosed with CRC, corresponding to 1.9 events/1000 person-years surveillance (95% CI 0.3 to 6.4). Conclusion The presence of SPs containing dysplasia, advanced adenomas and/or combined WHO criteria 1 and 3 phenotype is associated with CRC in patients with SPS. Patients with a history of smoking show a lower risk of CRC, possibly due to a different pathogenesis of disease. The risk of developing CRC during surveillance is lower than previously reported in literature, which may reflect a more mature multicentre cohort with less selection bias

Optimizing the Timing of Highest Hydrocortisone Dose in Children and Adolescents With 21-Hydroxylase Deficiency

CONTEXT: Hydrocortisone treatment of young patients with 21-hydroxylase deficiency (21OHD) is given thrice daily, but there is debate about the optimal timing of the highest hydrocortisone dose, either mimicking the physiological diurnal rhythm (morning), or optimally suppressing androgen activity (evening). OBJECTIVE: We aimed to compare 2 standard hydrocortisone timing strategies, either highest dosage in the morning or evening, with respect to hormonal status throughout the day, nocturnal blood pressure (BP), and sleep and activity scores. METHODS: This 6-week crossover study included 39 patients (aged 4-19 years) with 21OHD. Patients were treated for 3 weeks with the highest hydrocortisone dose in the morning, followed by 3 weeks with the highest dose in the evening (n = 21), or vice versa (n = 18). Androstenedione (A4) and 17-hydroxyprogesterone (17OHP) levels were quantified in saliva collected at 5 am; 7 am; 3 pm; and 11 pm during the last 2 days of each treatment period. The main outcome measure was comparison of saliva 17OHP and A4 levels between the 2 treatment strategies. RESULTS: Administration of the highest dose in the evening resulted in significantly lower 17OHP levels at 5 am, whereas the highest dose in the morning resulted in significantly lower 17OHP and A4 levels in the afternoon. The 2 treatment dose regimens were comparable with respect to averaged daily hormone levels, nocturnal BP, and activity and sleep scores. CONCLUSION: No clear benefit for either treatment schedule was established. Given the variation in individual responses, we recommend individually optimizing dose distribution and monitoring disease control at multiple time points

Validity of free testosterone calculation in pregnant women

Objective: Increased maternal testosterone concentration during pregnancy may affect the fetus. Therefore it is clinically relevant to have a quick and reliable method to determine free testosterone levels. Current calculators for free testosterone are suspected to perform poorly during pregnancy due to suggested competition between high levels of estradiol and free (bio-active) testosterone for sex hormone-binding globulin (SHBG) binding. Therefore, it is claimed that reliable calculation of free testosterone concentration is not possible. However, recent evidence on SHBG-binding sites questions the estradiol effect on the testosterone-SHBG binding during pregnancy. In this study, we investigated whether the free testosterone concentration can be calculated in pregnant women. Design and methods: Free testosterone was measured with a specially developed equilibrium dialysis method combined with liquid chromatography tandem mass spectrometry (LC-MS/MS). Free testosterone was also calculated with the formulas of Vermeulen et al. and Ross et al. Results: Total and free testosterone measured in healthy men and women were in good agreement with earlier reports. In pregnant women, total t estosterone values were higher than in non-pregnant women, whereas free testosterone values were comparable. Calculated free testosterone levels in pregnant women were highly correlated, but marginally higher, compared to measured free testosterone levels. Conclusions: We developed an equilibrium dialysis–LC-MS/MS method for the measurement of free testosterone in the low range of pregnant and non-pregnant women. Although during pregnancy total testosterone is increased, this is not the case for free testosterone. The free testosterone formulas perform well in pregnant women