Typical ultrasound features of various endometrial pathologies described using International Endometrial Tumor Analysis (IETA) terminology in women with abnormal uterine bleeding.

OBJECTIVE: To describe the ultrasound features of different endometrial and other intracavitary pathologies inpre- and postmenopausal women presenting with abnormal uterine bleeding, using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: This was a prospective observational multicenter study of consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler and fluid-instillation sonography were performed. Endometrial sampling was performed according to each center's local protocol. The histological endpoints were cancer, atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (EIN), endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma and other. For fluid-instillation sonography, the histological endpoints were endometrial polyp, intracavitary leiomyoma and cancer. For each histological endpoint, we report typical ultrasound features using the IETA terminology. RESULTS: The database consisted of 2856 consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler was performed in all cases and fluid-instillation sonography in 1857. In 2216 women, endometrial histology was available, and these comprised the study population. Median age was 49 years (range, 19-92 years), median parity was 2 (range, 0-10) and median body mass index was 24.9 kg/m2 (range, 16.0-72.1 kg/m2 ). Of the study population, 843 (38.0%) women were postmenopausal. Endometrial polyps were diagnosed in 751 (33.9%) women, intracavitary leiomyomas in 223 (10.1%) and endometrial cancer in 137 (6.2%). None (0% (95% CI, 0.0-5.5%)) of the 66 women with endometrial thickness < 3 mm had endometrial cancer or atypical hyperplasia/EIN. Endometrial cancer or atypical hyperplasia/EIN was found in three of 283 (1.1% (95% CI, 0.4-3.1%)) endometria with a three-layer pattern, in three of 459 (0.7% (95% CI, 0.2-1.9%)) endometria with a linear endometrial midline and in five of 337 (1.5% (95% CI, 0.6-3.4%)) cases with a single vessel without branching on unenhanced ultrasound. CONCLUSIONS: The typical ultrasound features of endometrial cancer, polyps, hyperplasia and atrophy and intracavitary leiomyomas, are described using the IETA terminology. The detection of some easy-to-assess IETA features (i.e. endometrial thickness < 3 mm, three-layer pattern, linear midline and single vessel without branching) makes endometrial cancer unlikely. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Abnormalities of acid-base balance and predisposition to metabolic acidosis in Metachromatic Leukodystrophy patients.

Metachromatic Leukodystrophy (MLD; MIM# 250100) is a rare inherited lysosomal storage disorder caused by the deficiency of Arylsulfatase A (ARSA). The enzymatic defect results in the accumulation of the ARSA substrate that is particularly relevant in myelin forming cells and leads to progressive dysmyelination and dysfunction of the central and peripheral nervous system. Sulfatide accumulation has also been reported in various visceral organs, although little is known about the potential clinical consequences of such accumulation. Different forms of MLD-associated gallbladder disease have been described, and there is one reported case of an MLD patient presenting with functional consequences of sulfatide accumulation in the kidney. Here we describe a wide cohort of MLD patients in whom a tendency to sub-clinical metabolic acidosis was observed. Furthermore in some of them we report episodes of metabolic acidosis of different grades of severity developed in acute clinical conditions of various origin. Importantly, we finally show how a careful acid-base balance monitoring and prompt correction of imbalances might prevent severe consequences of acidosis.

The -665 C>T polymorphism in the eNOS gene predicts cardiovascular mortality and morbidity in white Europeans.

We recently identified rs3918226 as a hypertension susceptibility locus (-665 C>T), TT homozygosity being associated with higher hypertension risk. T compared with C allele transfected cells had lower endothelial nitric oxide synthase (eNOS) expression. In the family-based Flemish Study on Environment, Genes and Health Outcomes (50.9% women; mean age 40.3 years), we investigated whether 32 TT homozygotes had worse outcomes than 2787 C allele carriers. Over 15 years (median), total and cardiovascular mortality and cardiovascular and coronary events amounted to 269 (9.5%), 98 (3.5%), 247 (8.8%) and 120 (4.3%), respectively. While accounting for family clusters, the hazard ratios associated with TT homozygosity were 4.11 (P=0.0052) for cardiovascular mortality (4 deaths), 2.75 (P=0.0067) for cardiovascular events (7 endpoints) and 3.10 (P=0.022) for coronary events (4 endpoints). With adjustment for cardiovascular risk factors, these hazard ratios were 6.01 (P=0.0003), 2.64 (P=0.0091) and 2.89 (P=0.010), respectively. Analyses unadjusted for blood pressure and antihypertensive treatment produced consistent results. For all fatal plus nonfatal cardiovascular events, the positive predictive value, attributable risk and population-attributable risk associated with TT homozygosity were 21.9, 61.5 and 2.0%, respectively. In conclusion, TT homozygosity at the position -665 in the eNOS promoter predicts adverse outcomes, independent of blood pressure and other risk factors.

Sonohysterographic endometrial sampling and hysteroscopic endometrial biopsy: a comparative study.

OBJECTIVES: To compare the quantity and quality of endometrial tissue sampled at saline contrast sonohysterography (SCSH) with that obtained by directed endometrial biopsy by operative hysteroscopy in patients with diffusely thickened and/or inhomogeneous endometrium at SCSH. A secondary aim was a comparison of the extent of procedure-related pain. METHODS: One hundred and twenty-eight patients with diffusely thickened (> 4 mm) and/or inhomogeneous endometrium at SCSH were prospectively recruited. Endometrial sampling was performed at the end of SCSH using the same 4.7-mm intrauterine catheter that had been used for saline instillation. These samples were compared to directed endometrial biopsies obtained with the guidance of an office 5-mm hysteroscope. After hysteroscopy, an extended guided curettage was performed under general anesthesia, providing specimens that were considered the gold standard for histological diagnosis. Endometrial specimen area (mm(2)), histologic concordance and procedure related pain (10-cm VAS) were compared for the two techniques. RESULTS: The median age of 88 pre- and of 40 post-menopausal patients was 41 (interquartile range, 34-48) years and 57 (interquartile range, 52-67) years, respectively. The median area of endometrial specimen obtained by SCSH was 25.1 (interquartile range, 12.4-52.3) mm(2) and was not significantly different from that obtained by hysteroscopy (16.9 (interquartile range, 10.0-52.7) mm(2)). The K values of the two different techniques for typical hyperplasia (n = 61) and for premalignant and malignant lesions (n = 26) were 0.91 and 0.94, respectively. Procedure-related pain was not significantly different between pre- and postmenopausal patients for both sampling techniques. CONCLUSIONS: SCSH with sampling proved to be as good as and as tolerable as hysteroscopic biopsy in cases with diffusely thickened and/or inhomogeneous endometrium. Both these imaging and biopsy techniques should be considered a reliable outpatient procedure in the management of patients with abnormal uterine bleeding. Published by John Wiley & Sons, Ltd.

Safety of sperm washing and ART outcome in 741 HIV-1-serodiscordant couples.

BACKGROUND: To evaluate the safety of sperm washing and assisted reproduction technique (ART) outcome offered to serodiscordant couples with a human immunodeficiency virus-1 (HIV-1)-positive male. METHODS: Sperm washing was performed and checked by RT-PCR on each semen sample before its fresh usage. Intrauterine insemination (IUI) or IFV/ICSI was offered according to fertility profile of each couple. Non-infected women underwent HIV testing 2 weeks before each procedure and for up to 6 months after. RESULTS: Seven hundred and forty-one couples entered the study of a possible 2011 serodiscordant couples counselled over 4 years. Superovulation and IUI were performed in 581 couples, where the pregnancy rate per cycle and pregnancy rate per couple were 19 and 78%, respectively, with multiple pregnancy rate being 4%. One hundred and sixty couples were treated by IVF/ICSI, where pregnancy rate per cycle and per couple were 22 and 41%, respectively, with multiple pregnancy rate being 10%. All female partners were still HIV-1 negative at follow-up. CONCLUSION: Sperm washing within a programme of reproductive counselling was proved to be safe in this large series of serodiscordant couples. The overall pregnancy rate (70.3%), independent of the procedure used (IUI or IVF/ICSI), justifies the effort of the medical team in setting up and implementing dedicated centres and of the individual patient in seeking a safe pregnancy.

Plasma ouabain-like factor during acute and chronic changes in sodium balance in essential hypertension.

An ouabain-like factor has been implicated repeatedly in salt-sensitive hypertension as a natriuretic agent. However, the response of plasma ouabain-like factor to acute and chronic variation of body sodium is unclear. We studied 138 patients with essential hypertension who underwent an acute volume expansion/contraction maneuver (2 days) and 20 patients who entered a blind randomized crossover design involving chronically controlled sodium intake and depletion (170 to 70 mmol/d; 2 weeks each period). In both studies, plasma levels of ouabain-like factor were higher during sodium depletion (acute: 338.8+/-17.4 and 402.7+/-22.8 pmol/L for baseline and low sodium, respectively, P<0.01; chronic: 320.4+/-32.0 versus 481.0+/-48.1 pmol/L, P=0.01). No significant change in plasma ouabain-like factor was observed after a 2-hour saline infusion (333.4+/-23.9 pmol/L) or controlled sodium (402.1+/-34.9 pmol/L). When patients were divided into salt-sensitive or salt-resistant groups, no differences in plasma ouabain-like factor were observed in the 2 groups at baseline or in response to the 2 protocols: salt resistant (n=69, 340.1+/-25.9 pmol/L) versus salt sensitive (n=69, 337.4+/-23.6 pmol/L) and chronic salt resistant (n=11, 336.0+/-53.2) versus salt sensitive (n=9, 301.1+/-331.4 pmol/L). However, circulating ouabain-like factor was increased by sodium depletion in both groups. These results demonstrate that circulating ouabain-like factor is raised specifically by maneuvers that promote the loss of body sodium. Acute expansion of body fluids with isotonic saline is not a stimulus to plasma ouabain-like factor. Moreover, basal levels of plasma ouabain-like factor do not differ among patients with salt-sensitive or salt-resistant hypertension. Taken together, these new results suggest that ouabain-like factor is involved in the adaptation of humans to sodium depletion and argue against the hypothesis that ouabain-like factor is a natriuretic hormone.

Alpha-adducin polymorphisms and renal sodium handling in essential hypertensive patients.

The relationship between blood pressure and sodium (Na) excretion is less steep in hypertension caused by increased renal tubular reabsorption. We recently demonstrated that one mutation in rat alpha-adducin gene: (1) is responsible for approximately 50% of the hypertension of MHS rats, and (2) stimulates tubular Na-K pump activity when transfected in renal epithelial cell, suggesting that its pressor effect may occur because an increased tubular reabsorption. Linkage and association studies demonstrated that the alpha-adducin locus is relevant for human hypertension. A point mutation (G460W) was found in human alpha-adducin gene, the 460W variant (G/W) is more frequent in hypertensives than in normotensives. The aim of this study was to test whether acute changes in body Na may differently affect blood pressure in humans as a function of alpha-adducin genotype. The pressure-natriuresis relationship was analyzed in 108 hypertensive using two different acute maneuvers: Na removal (furosemide 25 mg p.o.) and, two days later, Na load (310 mmoles i.v. in 2 hr). We found that 80 patients were wild-type homozygous (G/G), 26 were G/W heterozygous, and 2 were W/W homozygous with similar blood pressure, age body mass index, gender, plasma and urinary sodium and potassium. In basal condition G/W-W/W patients showed a lower plasma renin activity and fractional excretion of Na. In either case the pressure-natriuresis relationship was less sleep in G/W-W/W than in G/G patients, obviously negative for Na depletion with furosemide (-0.011 +/- 0.004 vs. -0.002 +/- 0.002 mm Hg/mumol/min, P < 0.03), and positive for Na load (0.086 +/- 0.02 vs. 0.027 +/- 0.007 mm Hg/mumol/min, P < 0.001). The finding of reduced slope after Na depletion or Na load supports the hypothesis that, as MHS rats, humans bearing one W alpha-adducin variant display an increased of renal tubular sodium reabsorption.

Polymorphisms of alpha-adducin and salt sensitivity in patients with essential hypertension.

BACKGROUND: Abnormalities in renal sodium transport may be involved in hypertension. Adducin, an alpha/beta heterodimeric protein found in the renal tubule is thought to regulate ion transport through changes in the actin cytoskeleton. We investigated whether an alpha-adducin polymorphism (Gly 460 Trp) is involved in essential hypertension in two separate populations. METHODS: Linkage analysis of three DNA markers at different distances from the alpha-adducin locus (20-2500 kb) was done in 137 hypertensive sibling-pairs. 477 hypertensive and 322 normotensive individuals were genotyped for the alpha-adducin polymorphism. The blood-pressure response to acute and chronic changes in sodium balance was studied in hypertensive individuals with and without the 460 Trp alpha-adducin allele. FINDINGS: Significant linkage was found for all three markers in the sibling-pair study. The extra shared alleles (9.1%, 6.5%, and 4.7%) and the significance level for linkage (p = 0.0006, p = 0.0119, and p = 0.0211) both decreased with increasing distance from the alpha-adducin locus. There was a significant association between the 460 Trp mutation and hypertension (p = 0.0003). In the salt-sensitivity test, to assess the acute blood-pressure response to changes in body sodium in 86 hypertensive patients, the decrease in mean arterial pressure was greater in 65 patients who were heterozygous for the mutant allele (Gly/Trp) than in 21 wild-type homozygotes (Gly/Gly) (mean decrease 15.9 [SE 2.0] vs 7.4 [1.3] mm Hg; p = 0.001). Similarly, 21 heterozygous hypertensive patients showed a greater fall in mean arterial pressure in response to 2 months' treatment with hydrochlorothiazide than did 37 wild-type homozygous hypertensive patients (mean decrease 14.7 [2.2] vs 6.8 [1.4] mm Hg; p = 0.002). INTERPRETATION: Our findings of significant linkage of the alpha-adducin locus to essential hypertension and greater sensitivity to changes in sodium balance among patients with the mutant allele suggest that alpha-adducin is associated with a salt-sensitive form of essential hypertension. We suggest the alpha-adducin polymorphism may identify hypertensive patients who will benefit from diuretic treatment or manoeuvres to reduce total body sodium.

Renal artery stenosis: value of screening with three-dimensional phase-contrast MR angiography with a phased-array multicoil.

PURPOSE: To evaluate screening with three-dimensional (3D) phase-contrast magnetic resonance (MR) angiography with a phased-array multicoil to detect renal artery stenosis. MATERIALS AND METHODS: Fifty consecutive patients suspected of having renovascular disease were prospectively examined with 3D phase-contrast MR imaging with a phased-array multicoil. Findings were correlated with those at intra-arterial digital subtraction angiography (DSA) as the standard of reference for grade of stenosis. RESULTS: MR angiography depicted 101 of 103 renal arteries depicted at intraarterial DSA; the two missed arteries were an accessory artery outside the imaging volume and an artery with a stent. At intraarterial DSA, a stenosis was found in 31 of 101 arteries. On the basis of findings at 3D phase-contrast MR angiography, the presence of any degree of stenosis was correctly depicted in 29 of 31 cases and the absence of stenosis was correctly depicted in 66 of 70 cases (accuracy, 94%; sensitivity, 94%; negative predictive value, 97%). Overall accuracy was 97% for correct depiction of severe renal artery stenosis (> 50%). CONCLUSION: 3D phase-contrast MR angiography with a phased-array multicoil was an accurate noninvasive screening technique in patients with suspected renal artery stenosis.