Citations

INTRODUCTION: Retained products of conception (POC) following uterine evacuation can lead to adverse sequelae, including hemorrhage, endometritis, intrauterine adhesions, and reoperation. Incidence of retained POC range from 1.5–3.7%. Use of procedural transvaginal sonography (TVUS) in the operating room has been proposed to help decrease this. METHODS: A retrospective review of first trimester uterine evacuation procedures from 1/2015–2/2017 was performed, noting use of transabdominal ultrasonography (TAUS), retained products of conception (sonographic findings requiring surgical or medical intervention), and complications. A practice change was implemented in May 2018, in which intra-procedural TVUS was routinely performed. A second retrospective chart review was conducted to assess for post-implementation incidence of retained POC, reoperation, and associated complications. Fisher's exact test was performed. RESULTS: Prior to implementation, 130 eligible procedures were performed during the specified timeframe, with 9/130 (6.9%) incidence of retained products of conception. TAUS was performed in 59/130 (45.4%) of procedures, and 4/9 (44.4%) of those with retained products. There were eight re-operative procedures in seven patients, and two patients were treated with misoprostol. Complications included hemorrhage, Asherman's and endometritis. Following implementation, 94 first trimester procedures were performed with transvaginal sonography, with 0 (0%) cases of retained POC (P=.01), no incidences of re-operation (P=.02), and one case of Asherman's. TVUS led to additional focused curettage in 20/94 (21.3%) of procedures. The endometrium was measured in 64 procedures, with a mean thickness of 5.5 mm (1–12 mm). CONCLUSION: Implementation of routine TVUS during uterine evacuation appears to reduce the incidence of retained POC and associated reoperation rates.

Background Ang‐(1‐12) is a primary non‐renin dependent substrate for direct tissue angiotensin II (Ang II) formation by chymase. This discovery challenges conventional thinking and explains the large residual risk of cardiovascular events in patients medicated with blockers of the renin angiotensin system (RAS). Here we report the first demonstration of circulating Ang‐(1‐12) as a biomarker of essential hypertension (EH) and cardio‐renal remodeling. Methods The cohort of patients from Olmsted County MN included 52 healthy adult volunteers (21 females), age 54 ± 8 years, and 23 essential hypertensive (EH) patients (14 females) age 61 ± 8 years with systolic blood pressure (SBP) ≥140 mm Hg prior to recruitment. Clinical examination, standardized BP measurements, and venous blood were obtained for measurements of plasma concentrations of angiotensinogen (AGT), Ang‐(1‐12), Ang II, aldosterone, renin activity, N‐terminal pro–B‐type natriuretic peptide (NT‐proBNP) and atrial and brain natriuretic peptides (ANP and BNP, respectively). All values are Means ± SD. Data were analyzed by 2‐way ANOVA for sex and hypertension. Results Plasma Ang‐(1‐12) levels in EHs [SBP: 134 ± 14 mm Hg; Ang‐(1‐12): 1,463 ± 446] were higher than normotensives [SBP: 117 ± 13 mm Hg; Ang‐(1‐12): 1,353 ± 379 fmol/mL, hypertension effect: P<0.05], irrespective of sex. Hypertension associated with increases in pulse pressure, PRA, and plasma AGT and NT‐proBNP concentrations (see Figure ). The elevation in circulating NT‐proBNP levels with hypertension was accounted for by a 4.6‐fold increase in hypertensive males (165 ± 134 pg/mL) while the 1.5‐fold rise in plasm NT‐proBNP did reach significance (134 ± 127 pg/mL, p> 0.05). Conclusions We show for the first time that Ang‐(1‐12) circulates in humans and its concentrations are elevated by chronic hypertension. We further demonstrate a sexual dimorphic pattern in hypertensives with respect to NT‐proBNP, the latter a biomarker for cardiac remodeling. Whether this represents a natriuretic system‐related compensatory mechanism, or worsening pathology, due to an elevated noncanonical RAS specific to male hypertensives remains to be studied. Further investigation to fully define the role of Ang‐(1‐12) as a cardiac disease biomarker in a larger, gender and ethnic diverse population and its relationship to hypertension and myocardial structure is warranted. Support or Funding Information Supported by grant HL‐051952 from the NHLBI of the NIH Lines are means ± SD Figure 1

Cardiorenal syndrome (CRS) is a multi‐organ disease, encompassing heart, kidney and vascular system dysfunction. CRS is a worldwide problem, with high morbidity, mortality, and inflicts a significant burden on the health care system. The pathophysiology is complex, involving interactions between neurohormones, inflammatory processes, oxidative stress and metabolic derangements. Therapies remain inadequate, mainly comprising symptomatic care with minimal prospect of full recovery. Challenges include limiting the contradictory effects of multi‐organ targeted drug prescriptions and continuous monitoring of volume overload. Novel strategies such as multi‐organ transplantation and innovative dialysis modalities have been considered but lack evidence in the CRS context. The adjunct use of pharmaceuticals targeting alternative pathways showing positive results in preclinical models also warrants further validation in the clinic. In recent years, studies have identified the involvement of gut dysbiosis, uraemic toxin accumulation, sphingolipid imbalance and other unconventional contributors, which has encouraged a shift in the paradigm of CRS therapy.

3567 Background: The ability to genotype large numbers of people rapidly and inexpensively for research purposes highlights the need to develop guidelines for providing medically-relevant research results - including unanticipated findings - to study participants. The Colon Cancer Family Registry (C-CFR) is the oldest and largest international colon cancer population-based registry; its experience managing genetic research findings can offer guidance to clinicians and researchers. The C-CFR has enrolled 10,019 cases with colon cancer and 24,708 family members in six registries in the US, Canada, Australia, and New Zealand. Deleterious (“high risk”) germline mutations have been identified in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) and the MutYH gene. The aims of this presentation are to: (1) report the uptake of genetic test results by C-CFR participants; (2) systematically compare disclosure protocols and barriers to uptake by registry; (3) make recommendations to guide clinicians and researchers. Methods: Uptake of genetic test results was calculated from data collected by the C-CFR; key investigators (KIs) from each registry completed a survey about disclosure decision-making; KIs also took part in discussions to generate recommendations. Results: Registry-wide molecular testing has identified deleterious MMR germline mutations for at least one member of 424 families (4%) and 48 biallelic MutYH gene carriers. Uptake of test results ranged from 56-86% (n= 1542) across registries. Barriers to disclosure include: (1) lack of pre-existing notification protocols; (2) logistics of re-consent; (3) limited involvement of genetic counselors at some registries; (4) in the US, the requirement that genetic testing be performed in a CLIA approved laboratory; (5) IRBs declining approval; and (6) budget constraints. Conclusions: Based on our international registry’s findings we recommend that researchers generating genetic information establish plans for disclosure at the outset; obtain subject consent a priori; consider subject knowledge and disclosure preferences; provide guidance and budget for clinical follow-up; and involve genetic counselors.

Objective: To describe reported outcomes of nonsurgical radiologic interventions for abdominal wall endometriosis in comparison with surgery where available. Data sources: A systematic search of Ovid Medline, Embase, PubMed, and Cochrane Controlled Register of Trials was performed from inception to January 2019 with no language restrictions. Study eligibility criteria: Studies were included if they evaluated a nonsurgical intervention in women with symptomatic abdominal wall endometriosis with both comparative and noncomparative study designs. Study appraisal and synthesis methods: Titles and abstracts were reviewed for relevance, and full-text articles were obtained and evaluated for inclusion, all in duplicate. Meta-analysis was performed when possible using a fixed effects model. Results: Of the 114 records reviewed, 16 full-text articles were assessed and 7 were included in analysis. The standard mean difference between pre- and post-intervention pain scores was similar between ultrasound-guided high-intensity focused ultrasound (USgHIFU) (−3.00; 95% confidence interval −3.34, −2.66) and cryoablation (−3.93; 95% confidence interval −5.73, −2.12). The mean percent decrease in lesion size following intervention was similar between USgHIFU (−61.38%; 95% confidence interval −78.64%, −44.11%), and cryoablation (−88.16%; 95% confidence interval −83.90%, −55.06%). When compared with surgical excision, mean length of stay was 2.78 days less in the nonsurgical intervention group (95% confidence interval −3.78, −1.79). Conclusions: Both USgHIFU and cryoablation are effective at reducing pain scores and lesion size in abdominal wall endometriosis. Mean length of stay was significantly less following a nonsurgical radiologic intervention for abdominal wall endometriosis compared with surgery. More studies are needed comparing complication and recurrence rates between nonsurgical radiologic interventions for abdominal wall endometriosis and surgery.

Based on the cardiac hormone atrial natriuretic peptide (ANP) and its seminal role in blood pressure (BP) homeostasis, we investigated the chronic BP lowering actions of a novel ANP analog currently entering clinical trials for hypertension. Previous reports demonstrate that this analog MANP activates the guanylyl cyclase A receptor (GC-A) and results in more potent biological actions compared with ANP; thus, it may represent a new therapeutic drug for hypertension. A major goal of this study was to establish that chronic subcutaneous delivery of MANP is feasible and hypotensive together with cGMP effects. We investigated the BP-lowering and cGMP-activating actions of acute and chronic subcutaneous delivery in normal and hypertensive rats. Furthermore, we explored vascular mechanisms of MANP in human aortic smooth muscle cells (HASMC) and ex vivo in isolated arteries. In normal rats with a single subcutaneous injection, MANP promoted robust dose-dependent BP-lowering actions and natriuresis, together with cGMP activation. Most importantly in hypertensive rats, once-a-day subcutaneous injection of MANP for 7 days induced cGMP elevation and long-term BP reduction compared with vehicle. Mechanistically, in HASMC, MANP activated cGMP and attenuated angiotensin II-mediated increases in intracellular Ca2+levels while directly vasorelaxing arterial rings. Our study demonstrates for the first time the effectiveness of subcutaneous administration of MANP for 7 days and provides innovative, vascular mechanisms of BP regulation supporting its continued development as a novel therapeutic for hypertension.

Abstract This study was designed to test the hypothesis that, in a patient with decreased renal function and an increased plasma creatinine concentration, a significant quantity of creatinine is excreted into the gut, as is true of urea and uric acid, and is metabolized by gut flora. [Methyl-14C] creatinine was given intravenously to five patients and [methyl-14C] creatinine or [carbonyl-14C] creatinine was given orally to five patients. Extracts of excreta, plasma, and urine were subjected to ion-exchange chromatography, with monitoring for 14C and for ninhydrin-positive material. Respiratory gases, collected in acid and base, were assayed for radioactivity. Blood specimens were obtained at intervals to furnish data on decay of labeled creatinine in the body pool. The data show that there is a true creatinine deficit (15.9 to 65.7% of the creatinine formed is metabolized or excreted via extrarenal routes) in patients with decreased renal function. In these patients, creatinine is metabolized to CO2 and methylamine, presumably by the microflora of the gut. A significant portion of the carbonyllabeled creatinine appeared in plasma in an unidentified compound.

Abstract "Creatininase" activity was induced in the colon flora of rats by feeding creatinine. Sarcosine and methylamine were tentatively identified as the major products of the enzymic action. A third (unidentified) compound was observed. These compounds and methylguanidine were labeled in the urine of rats given 14CH3-creatinine orally. The results suggest that creatinine should not be considered biologically inert in animals, especially in those with decreased renal function.