Improved technical success, postnatal outcome and refined predictors of outcome for fetal aortic valvuloplasty.

OBJECTIVES: Fetal aortic valvuloplasty (FAV) may prevent progression of mid-gestation aortic stenosis to hypoplastic left heart syndrome (HLHS). The aim of this study was to evaluate whether technical success and biventricular (Biv) outcome after FAV have changed from an earlier (2000-2008) to a more recent (2009-2015) era and identify pre-FAV predictors of Biv outcome. METHODS: We evaluated procedural and postnatal outcomes in 123 fetuses that underwent FAV for evolving HLHS at Boston Children's Hospital between 2000 and 2015. The primary outcome measure was circulation type (Biv vs single ventricle) at the time of neonatal hospital discharge. Classification and regression tree (CART) analysis was performed to construct a stratification algorithm to predict Biv circulation based on pre-FAV fetal variables. RESULTS: The FAV procedure was technically successful in 101/123 (82%) fetuses, with a higher technical success rate in the more recent era than in the earlier one (49/52 (94%) vs 52/71 (73%); P = 0.003). In liveborn patients, the incidence of Biv outcome was higher in the recent than in the earlier era, both in the entire liveborn cohort (29/49 (59%) vs 16/62 (26%); P = 0.001) and in those in whom the procedure was technically successful (27/46 (59%) vs 15/47 (32%); P = 0.007). Independent predictors of Biv outcome were higher left ventricular (LV) pressure, larger ascending aorta, better LV diastolic function and higher LV long-axis Z-score. On CART analysis, fetuses with LV pressure > 47 mmHg and ascending aorta Z-score ≥ 0.57 had a 92% probability of Biv outcome (n = 24). Those with a lower LV pressure, or mitral dimension Z-score < 0.1 and mitral valve inflow time Z-score < -2 (n = 34) were unlikely to have Biv (probability of 9%). The remainder of the patients had an intermediate (∼40-60%) likelihood of Biv circulation. CONCLUSIONS: The proportion of patients achieving Biv outcome after FAV has increased, probably owing to an improved technical success rate and modified selection criteria. Fetal factors, including LV pressure, size of the ascending aorta and diastolic function, are associated with likelihood of Biv circulation after FAV. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

N-formylpenicillamine and penicillamine as degradation products of penicillins in solution.

The degradation of several penicillins in unbuffered aqueous solution produces N-formylpenicillamine, in some cases in high yield. Very little or no penicillamine is formed under these conditions. N-Formylpenicillamine was produced from benzylpenicillin at pH values between 2.5 and 7, with a maximum yield of 30% at pH 5, whereas penicillamine was produced only at pH 5 or below in a yield of less than 1%. Benzylpenicillenic acid at pH 5 gave a 20% yield of N-formylpenicillamine and no penicillamine whereas benzylpenicilloic, penilloic and penillic acids gave no N-formylpenicillamine and a small amount of penicillamine.

Structure re-assignment of a metabolite of ampicillin and amoxycillin and epimerization of their penicilloic acids.

Products formed in-vitro from ampicillin and amoxycillin penicilloates have been examined by high-performance liquid chromatography, ultraviolet and nuclear magnetic resonance spectroscopy and thiol group determination and were found to be the 5S epimers of the penicilloic acids. This is in contrast to a published claim that the corresponding penamaldic acids were formed by the treatment used.

n-3 fatty acid enriched table eggs: a survey of consumer acceptability.

Table eggs enriched with n-3 fatty acids may provide an alternative to fish as a source of these proposed healthful fatty acids. Successful marketing of this product may be influenced, however, by consumer perceptions of the egg as an unhealthful food. Therefore, the objectives of the current study were to assess consumer perceptions of table egg health quality and to determine the potential consumer acceptability of an n-3 fatty acid-enriched table egg. A survey was conducted in five major Texas cities; over 500 consumers completed the survey. Data were analyzed using the chi-square procedure. The majority of consumers surveyed considered eggs healthful and reported purchasing eggs at least once monthly and consuming an average of three whole eggs per week, as compared with an average reported fish consumption of only one serving per week. Sixty-five percent of the consumers reported willingness to purchase an n-3 fatty acid-enriched table egg and of these, 71% were willing to pay an additional $.50 per dozen. These data indicate that n-3 fatty acid-enriched table eggs represent a viable means of incorporating n-3 fatty acids into the diet of health-conscious consumers.

A review of ductal stenting in hypoplastic left heart syndrome: bridge to transplantation and hybrid stage I palliation.

There is increasing interest in applying ductal stenting technology to high-risk patients with hypoplastic left heart syndrome (HLHS). In this review, we present the complete history and a comprehensive up-to-date analysis of all available data on the use of ductal stenting as part of various hybrid strategies for the combined medical and surgical management of HLHS.

Changes in left heart hemodynamics after technically successful in-utero aortic valvuloplasty.

OBJECTIVE: Severe aortic stenosis in the mid-gestation fetus can progress to hypoplastic left heart syndrome (HLHS). @ In-utero aortic valvuloplasty is an innovative therapy to promote left ventricular growth and function and potentially to prevent HLHS. This study evaluated the effects of mid-gestation fetal balloon aortic valvuloplasty on subsequent fetal left ventricular function and left heart Doppler characteristics. METHODS: We reviewed fetuses with aortic stenosis that underwent attempted in-utero aortic valvuloplasty between 2000 and 2006. Pre-intervention and the latest post-intervention fetal echocardiograms were analyzed to characterize changes in left heart function and Doppler characteristics in utero. RESULTS: Forty-two fetuses underwent attempted aortic valvuloplasty during the study period, 12 of which were excluded from analysis secondary to inadequate follow-up data, termination or fetal demise. Study fetuses (n = 30) underwent pre-intervention echocardiography at a median gestational age of 23 weeks, and were followed for a median of 66 +/- 23 days post-intervention. In 26 fetuses, aortic valvuloplasty was technically successful. Among these 26, left heart physiology was abnormal pre-intervention and improved or normalized after intervention in most cases: biphasic mitral inflow was present in 5/25 (20%) cases pre-intervention and in 21/23 (91%) post-intervention (P < 0.001); moderate or severe mitral regurgitation was present in 14/26 (54%) cases pre-intervention and in 5/23 (22%) post-intervention (P = 0.02); bidirectional flow across the patent foramen ovale was present in 0/26 cases pre-intervention and in 6/25 (24%) post-intervention (P = 0.01); antegrade flow in the transverse arch was present in 0/25 cases pre-intervention and in 17/26 (65%) post-intervention (P < 0.001). The left ventricular ejection fraction increased from 19 +/- 10% pre-intervention to 39 +/- 14% post-intervention (P < 0.001). These changes were not observed in control fetuses (n = 18). CONCLUSION: Fetal aortic valvuloplasty, when technically successful, improves left ventricular systolic function and left heart Doppler characteristics.

Factors affecting technical success of fetal aortic valve dilation.

OBJECTIVE: We have reported previously that valve dilation enhances growth of cardiac structures and may prevent hypoplastic left heart syndrome (HLHS) in fetuses with critical aortic stenosis. We aimed to investigate maternal/fetal factors which may affect the technical success of fetal valvuloplasty, and to describe perinatal complications of the procedure. METHODS: This was a descriptive series of 22 fetuses diagnosed with critical aortic stenosis developing into HLHS which underwent intervention by valvuloplasty. Initially this was attempted using a percutaneous approach; reassessment after our first five attempts, only one of which was successful, led to the introduction of the option of laparotomy. Technical success was defined as balloon inflation across the aortic annulus and a broader jet through the aortic valve as assessed by Doppler. Data collected included body mass index, demographic variables, ultrasound findings and postprocedure interventions. RESULTS: Technical success increased significantly if maternal laparotomy was an option (83.3% vs. 20.0%, P = 0.017). Laparotomy was performed in 66.6% (12/18) of cases. There was a learning curve that showed an increase in success rate and decrease in need for laparotomy over the 3-year study period. Neither the need for laparotomy nor the chances of technical success were predictable by gestational age, body mass index or placental location. Tocolysis was limited to perioperative prophylaxis; one woman experienced wound infection and fluid overload. Postoperatively, three fetuses died and two delivered prematurely, 2 and 7 weeks after intervention. CONCLUSION: Fetal aortic valvuloplasty can be performed with technical success, with low fetal loss rate and few maternal complications. While the need for laparotomy cannot be predicted, having it available as an option improves the technical success rate.

Structural and compliant anatomy of the patent foramen ovale in patients undergoing transcatheter closure.

BACKGROUND: Most current intracardiac closure devices target the atrial septal defect. However, defects such as the patent foramen ovale (PFO) have unique structural features that may influence rational device design. With mounting interest in transcatheter techniques for closure of PFO in patients with cryptogenic stroke, a clearer understanding of these features is warranted. METHODS: Retrospectively, we reviewed angiograms obtained at the time of transcatheter closure of PFOs with a non-self-centering device in a group of 21 patients with a history of stroke. RESULTS: The PFO appeared as a tunnel of varying length (2.4 to 19.5 mm, mean 9.1 +/- 4.7 mm) bounded by septum secundum and septum primum. The potential area of the defect was as small as 12.2 mm(2) and as large as 121.1 mm(2). With device placement, the tunnel length shortened or disappeared (0.5 +/- 1.6 mm) by inferior displacement of the more compliant septum primum. CONCLUSIONS: In patients with PFO referred for transcatheter closure, the defect most commonly appeared as a tunnel-like defect between a thicker, less compliant septum secundum and a thinner, more compliant septum primum. Although the length of the undisturbed tunnel varied widely, the tunnel was shortened or eliminated by placement of a non-self-centering device. The observation that PFO anatomy can be predictably altered by some devices may have an impact on device design or implantation technique.

Changes in cerebral blood volume with changes in position in awake and anesthetized subjects.

UNLABELLED: Changes in posture affect cerebral blood volume (CBV), and moderate head-up tilt is used as a therapeutic maneuver to reduce CBV and intracranial pressure. However, CBV is rarely measured in the clinical setting. Near-infrared spectroscopy allows real-time bedside monitoring of cerebral hemodynamics, and we have used this technique to measure changes in CBV with changes in posture in 10 normal subjects and 10 propofol-anesthetized patients. In the awake subjects, changes in CBV were correlated with the degree of table tilt. CBV decreased with 18 degrees head-up tilt and increased with 18 degrees head-down tilt (P < 0.0001, r = -0.924). In anesthetized patients, there were differences between head-up and head-down tilt. In the head-down position, CBV was also correlated with the degree of table tilt (P < 0.001, r = -0.782), whereas there was a clinically insignificant reduction in CBV in the head-up position. Near-infrared spectroscopy allows continuous, real time measurement of changes in CBV at the bedside. IMPLICATIONS: Near-infrared spectroscopy, a bedside technique, has been used to measure changes in cerebral blood volume in normal subjects. We have used the same technique in anesthetized patients and have shown that, when a patient is placed in the head up position, the decrease in cerebral blood volume is attenuated, relative to normal subjects.

Early results and medium-term follow-up of stent implantation for mild residual or recurrent aortic coarctation.

BACKGROUND: Optimal timing and mode of treatment for patients with aortic coarctation remains controversial, particularly when the degree of obstruction is mild. Surgery, balloon dilatation, and stent implantation have all proven effective in the treatment of moderate or severe obstruction. In this report, we describe the use of stents to treat coarctation in a heterogeneous population, including patients with relatively mild obstruction. METHODS: Retrospectively, we studied the results of stent implantation in 33 patients, children and young adults, who underwent catheterization for treatment of coarctation. Patients with isolated coarctation, as well as those with associated cardiac defects, were included. The median systolic pressure gradient of our patients was 25 mm Hg. RESULTS: Patients had an acute decrease in systolic blood pressure gradient (25 mm Hg to 5 mm Hg, P <.001) and an increase in lumen diameter (8 mm to 13 mm, P <.001). When 16 patients were recatheterized during the follow-up period, gradients remained decreased (30 mm Hg to 14 mm Hg, P <.001) compared with prestent values. Ventricular end-diastolic pressure, which was increased in 82% of patients at the time of initial catheterization, decreased from 17 mm Hg to 14 mm Hg (P =.002). Although the procedure was generally safe, serious complications did occur. CONCLUSIONS: Stent implantation represents a therapeutic option that can safely and effectively reduce gradient in challenging patients with mild postoperative coarctation. Furthermore, our data suggest that aortic obstruction often coexists with ventricular diastolic dysfunction in these patients and that relief of obstruction may play a role in improvement of function.

Culture of mid catheter urine collected via an open-ended catheter: a reliable guide to bladder bacteriuria.

Colony counts were compared from urine samples obtained by suprapubic aspiration and via a short, wide bore, open-ended urethral catheter. We studied 30 female patients in whom suprapubic aspiration of bladder urine was necessary to confirm the presence of bacteriuria with conventional or fastidious organisms. Catheterization was done immediately following suprapubic aspiration. Culture results of mid catheter urine specimens were similar to those from suprapubic aspiration urine specimens in 27 of 30 patients, a result considerably superior to that obtained with a conventional side-hole catheter. We conclude that a short, wide bore, open-ended catheter should be used to obtain urine specimens from female patients. Results confirm catheter specimens to be a satisfactory alternative to bladder aspiration of urine for detection of bacteriuria caused by fastidious micro-organisms or in patients with low numbers of conventional urinary tract pathogens.

Inhibition of metallo-beta-lactamases by a series of mercaptoacetic acid thiol ester derivatives.

A series of mercaptoacetic acid thiol esters have been identified as metallo-beta-lactamase inhibitors. Electrospray mass spectrometry (ESMS) has shown that irreversible inhibition of the Bacillus cereus II metallo-beta-lactamase by SB214751, SB214752, and SB213079 was concomitant with a 90-Da increase in mass of the enzyme. Tryptic digestion of the B. cereus II inhibited with SB214751 illustrated that the peptide fragment, containing the only cysteine of the enzyme, had undergone a mass increment of 90 Da. It was further demonstrated that B. cereus II hydrolyzed this type of compound across the thiol ester bond to yield mercaptoacetic acid. Mercaptoacetic acid is the only molecular fragment common to SB214751, SB214752, and SB213079, and free mercaptoacetic acid does not bind covalently to B. cereus II. Therefore, it is concluded that these compounds inhibit B. cereus II by the mechanism-based delivery of mercaptoacetic acid, forming a disulfide linkage with the active sites cysteine (predicted mass shift = +90 Da) under the aerobic conditions of the assay. The different thiol esters examined had a broad range of potencies against the metallo-beta-lactamases tested. For example SB214751, SB214752, and SB213079 all had 50% inhibitory concentrations of < 10 and > 1,000 microM for the Stenotrophomonas maltophilia L-1 and Bacteroides fragilis CfiA enzymes, respectively. SB216968 was particularly active against the Aeromonas hydrophila CphA metallo-beta-lactamase and was found to be an uncompetitive inhibitor of this enzyme (Ki = 3.9 microM), whereas it exhibited irreversible inhibition of the L-1 enzyme. These observations with this series of compounds have revealed subtle differences between the active sites of different metallo-beta-lactamases. Finally, a novel application for isothermal titration calorimetry for assessing the zinc chelating activity of candidate inhibitors is also presented.