Stillbirths: how can health systems deliver for mothers and babies?

The causes of stillbirths are inseparable from the causes of maternal and neonatal deaths. This report focuses on prevention of stillbirths by scale-up of care for mothers and babies at the health-system level, with consideration for effects and cost. In countries with high mortality rates, emergency obstetric care has the greatest effect on maternal and neonatal deaths, and on stillbirths. Syphilis detection and treatment is of moderate effect but of lower cost and is highly feasible. Advanced antenatal care, including induction for post-term pregnancies, and detection and management of hypertensive disease, fetal growth restriction, and gestational diabetes, will further reduce mortality, but at higher cost. These interventions are best packaged and provided through linked service delivery methods tailored to suit existing health-care systems. If 99% coverage is reached in 68 priority countries by 2015, up to 1·1 million (45%) third-trimester stillbirths, 201?000 (54%) maternal deaths, and 1·4 million (43%) neonatal deaths could be saved per year at an additional total cost of US$10·9 billion or $2·32 per person, which is in the range of $0·96-2·32 for other ingredients-based intervention packages with only recurrent costs.     

Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis

BACKGROUND & AIMS: An attenuated form of familial adenomatous polyposis has been described, but the phenotype remains poorly understood. METHODS: We performed genetic testing on 810 individuals from 2 attenuated familial adenomatous polyposis kindreds harboring an identical germline adenomatous polyposis coli gene mutation. Colonoscopy was performed on mutation-positive persons. RESULTS: The disease-causing mutation was present in 184 individuals. Adenomatous polyps were present in 111 of 120 gene carriers who had colonoscopy at an average age of 41 years. The median number of adenomas was 25 (range, 0-470), with striking variability of polyp numbers and a proximal colonic predominance of polyps. Colorectal cancer occurred in 27 mutation carriers (average age, 58 years; range, 29-81 years), with 75% in the proximal colon. The cumulative risk of colorectal cancer by age 80 was estimated to be 69%. An average of 3.4 recurrent polyps (range, 0-29) were found in the postcolectomy rectal remnant over a mean of 7.8 years (range, 1-34 years), with 1 rectal cancer. CONCLUSIONS: This investigation shows that attenuated familial adenomatous polyposis in the kindreds examined shows a much smaller median number of polyps than typical familial adenomatous polyposis, a wide variability in polyp number even at older ages, and a more proximal colonic location of polyps and cancer, yet it is associated with an extremely high risk of colon cancer. The phenotype of attenuated familial adenomatous polyposis mimics typical familial adenomatous polyposis in some cases but in others is difficult to distinguish from sporadic adenomas and colorectal cancer, thus making genetic testing particularly important.     

Use of an ultrasonic contrast method in the diagnosis of valvular regurgitation and intracardiac shunts

Injection of normal saline solution or indocyanine green dye through intracardiac catheters results in ultrasonic reflections from the site of injection. To evaluate the diagnostic usefulness of this observation, ultrasonic transducers were first placed directly on the pulmonary artery or ascending aorta of six open chest dogs. The rapid injection of 5 ml of normal saline solution into the femoral vein or left atrium produced a “cloud” of contrast echoes filling the pulmonary artery or ascending aorta. Thus, the echo-reflecting phenomenon persists during the passage of blood across two cardiac valves. Sixty-two patients aged 2 months to 70 years were then studied during cardiac catheterization; recordings were made during injection of indocyanine green dye or normal saline solution. Contrast echoes appeared in the left atrium after left ventricular injection in 14 of 16 patients with mitral regurgitation. Aortic root injection produced contrast echoes in the left ventricle in 13 of 16 patients with aortic regurgitation. Valvular regurgitation as small as 10 percent by angiographic determination was detected. Shunting was detected In patients with atrial and ventricular septal defects, patent ductus arteriosus and tetralogy of Fallot. Catheter-induced mitral regurgitation was demonstrated in one patient. This method is a sensitive and accurate qualitative technique for detecting intracardiac shunts and valvular regurgitation.     

Insulin-like growth factor-binding protein-3 is associated with the presence and extent of coronary arteriosclerosis

Aging is associated with the progression of arteriosclerosis and the decline of several endocrine functions. We therefore investigated the association of coronary arteriosclerosis with hormones, the serum concentrations of which change during aging. Coronary angiograms of 189 men <70 years old were evaluated by 3 semiquantitative score systems to estimate the extent of focal and diffuse vessel wall alterations. Fasting sera were analyzed for levels of glucose, lipids, thyroid-stimulating hormone, insulin, insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), dehydroepiandrosterone sulfate (DHEAS), testosterone, and sex hormone-binding globulin (SHBG). After adjustment for age, body mass index, and waist-to-hip ratio, 92 patients with >/=1 stenoses >70% differed from 97 patients without such focal lesions by higher serum levels of glucose, total and LDL cholesterol, and apolipoprotein (apo) B, as well as by lower serum levels of IGFBP-3. Multivariate analyses revealed significant and independent correlations of all 3 coronary scores with LDL cholesterol (or apoB) and IGFBP-3; of 2 coronary scores with age, glucose, and insulin; and of 1 score with IGF-I. No significant correlations existed for waist-to-hip ratio (or body mass index) and DHEAS (or testosterone or SHBG). IGFBP-3 explained 9% to 14% and 3.5% to 10% of the variances of focal and diffuse lesions, respectively. In conclusion, IGFBP-3 and, with much less strength and consistency, insulin and IGF-I, but not markers of hypothyroidism, adrenopause, and andropause, have statistically significant and independent associations with coronary arteriosclerosis in men.     

Detection of missense mutations in the genes for lipoprotein lipase and hepatic triglyceride lipase in patients with dyslipidemia undergoing coronary angiography

Coronary events have a close association with a low HDL/hypertriglyceridemia (LHDL/HTG) phenotype. As enzymes that hydrolyze triglyceride-rich lipoproteins are associated with a modulation of both HDL cholesterol and triglycerides, we have tested the hypothesis that mutations in the genes encoding lipoprotein lipase (LPL) or hepatic lipase (HTGL) may contribute to the formation of coronary atherosclerosis and, thus, of coronary heart disease (CHD). The entire coding and boundary regions of LPL and HTGL genes were analyzed by direct sequencing in 20 patients with both LHDL/HTG and diagnosed CHD. In the LPL gene six different polymorphisms were identified with same frequencies observed in the general population. In the HTGL gene, besides several polymorphisms, we identified three missense mutations: Asn37His, Val73Met, and Ser267Phe. Population screening using allele specific PCR identified Val73Met as a polymorphism while the two others were absent from 100 control individuals. One of the mutations (Ser267Phe) is known to cause HTGL deficiency and is associated with type III hyperlipoproteinemia. Since this dyslipoproteinemia meets the criteria of LHDL/HTG, it is intriguing to speculate that missense mutations in HTGL may play a role in the pathogenesis of this atherogenic phenotype.     

Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries.

Plasma concentration of markers of inflammation are increased in patients with atherosclerosis. However, it is unclear whether the pattern and magnitude of this increase vary with the site and extent of disease. In 147 patients undergoing semiquantitative coronary angiography, we measured the acute-phase reactants C-reactive protein (CRP) or serum amyloid A (SAA); the proinflammatory cytokine interleukin 6 (IL-6); the active and total fractions of the anti-inflammatory cytokine transforming growth factor-beta (TGF-beta); the macrophage activation marker neopterin; and the infection marker procalcitonin. Compared with 62 patients without either coronary artery disease (CAD) or peripheral artery disease (PAD), 57 patients with CAD but no PAD showed greater median CRP (0. 4 versus 0.2 mg/dL, P=0.004) and IL-6 (3.8 versus 1.6 pg/mL, P=0. 007) levels and a lower level of active-TGF-beta (57 versus 100 ng/mL, P=0.038). Moreover, CRP, IL-6, and neopterin levels showed a positive and the active TGF-beta level a negative correlation with the extent of coronary atherosclerosis. Compared with these 57 patients with CAD alone, 15 patients with PAD and CAD had higher median levels of SAA (17 versus 7 mg/mL, P=0.008), IL-6 (12 versus 4 pg/mL, P=0.002), neopterin (14 versus 11 mg/dL, P=0.006), and total TGF-beta (11834 versus 6417 ng/L, P=0.001). However, these strong univariate associations of markers of inflammation and atherosclerosis were lost in multivariate analysis once age, sex, and high density lipoprotein cholesterol or fibrinogen were taken into account. Increased plasma levels of CRP, SAA, IL-6, TGF-beta, neopterin, and procalcitonin constitute an inflammatory signature of advanced atherosclerosis and are correlated with the extent of disease but do not provide discriminatory diagnostic power over and above established risk factors.     

Drug Coated Balloon Is Less Effective for Treatment of DES In‐Stent Restenosis Both in Native Coronary Arteries and Saphenous Vein Grafts: Results From a Bicenter Registry

Background

The paclitaxel drug coated balloon (DCB) is an established treatment for bare metal stent (BMS) in‐stent restenosis (ISR) in native coronary arteries. The evidence of DCB‐application for drug eluting stent (DES) ISR both in native coronaries and saphenous vein grafts (SVG) is limited. Aim of our study was to compare the differential efficacy of DCB for treatment of BMS‐ and DES‐ISR in native coronary vessels and SVGs.

Methods and Results

N = 135 DCB‐treated patients with available follow up (FU) angiography were included in this retrospective study. Patients received treatment between April 2009 and March 2013 at 2 tertiary care hospitals in Germany. DCB was applied in BMS‐ISR (n = 65; 48%) and DES‐ISR (n = 70; 52%). DCB‐treated lesions were located in native coronary arteries (n = 110; 81%; BMS‐ISR: n = 58; 53%; DES‐ISR: n = 52; 47%) and SVGs (n = 25; 19%; BMS‐ISR: n = 7, 28%; DES‐ISR: n = 18, 72%). Median FU was 12 months. Endpoints were binary restenosis and target lesion revascularization (TLR). Binary restenosis (29% vs. 57%; P < 0.01) and TLR (18% vs. 46%; P < 0.01) were significantly more frequent in DES‐ISR versus BMS‐ISR. In SVGs, TLR was required in 72% (DES‐ISR) versus 14% (BMS‐ISR); P = 0.02. In the Kaplan–Meier‐analysis freedom from both endpoints was significantly decreased in the DES‐lesions both in the total population (binary restenosis P < 0.01; TLR P < 0.01) and native coronaries (binary restenosis P = 0.02; TLR P = 0.04).

Conclusions

DCB treatment is less effective in DES‐ISR than in BMS‐ISR. The diminished efficacy of DCB treatment is even more pronounced in DES‐ISR located within degenerated SVGs.

     

Influence of experience on procedure steps,safety, and functional results in edge to edge mitral valve repair—a single center study

Objectives: We sought to determine the effects of experience on the Mitraclip^® procedure steps as well as procedure safety and functional results. Background: MR has proven deleterious in heart failure. Mitraclip^® therapy evolved an important option in patients with severely reduced left ventricular function (LVEF). Methods: Between 2011 and 2016, 126 consecutive patients were grouped in three groups and investigated in a prospective observational study. We evaluated the duration of procedural steps, safety endpoints, and functional results. Results: The median logistic EuroScore was 32% (7–40%). Ninety‐five percent of patients were in NYHA‐stage ≥III and 51% had a LVEF <30%. Groups were homogeneous as to their baseline NYHA status and right heart catheterization data. Echocardiography data are comparable, albeit with a decreasing effective regurgitant orifice area (0.44 ± 0.21 group I vs. 0.34 ± 0.22 group III, P = 0.02). Frailty was less frequent and baseline 6 min walking test results improved from group I to group III. Duration of a first clip placement decreased from 106 ± 50 to 50 ± 21 min (P < 0.001). Total procedure time decreased from 221 ± 70 to 144 ± 68 (P < 0.001). The number of clips implanted increased from 66 to 79 (P = 0.02). MitraClip^® implantation was effective in either group but the combined safety endpoint was reached less frequent in group III (P = 0.01). There was no difference in MACCE rate, 30 day‐ or intrahospital‐mortality between groups. Conclusion: Safety and duration of procedure steps improved substantially with experience. MR reduction was sustained from the beginning without further improvement. Patient selection is a key factor for success. © 2016 Wiley Periodicals, Inc.     

Encircling overlapping multipulse shock waveforms for transthoracic defibrillation

Objectives. This study was performed to determine the efficacy of new encircling overlapping multipulse, multipathway waveforms for transthoracic defibrillation.

Background. Alternative waveforms for transthoracic defibrillation may improve shock success.

Methods. First, we determined the shock success achieved by three different waveforms at varying energies (18–150 J) in 21 mongrel dogs after short-duration ventricular fibrillation. The waveforms tested included the traditional damped sinusoidal waveform, a single pathway biphasic waveform, and a new encircling overlapping multipulse waveform delivered from six electrode pads oriented circumferentially. Second, in 11 swine we compared the efficacy of encircling overlapping multipulse shocks given from six electrode pads and three capacitors versus encircling overlapping shocks given from a device utilizing three electrodes and one capacitor.

Results. In the first experiment, the encircling overlapping waveform performed significantly better than biphasic and damped sinusoidal waveforms at lower energies. The shock success rate of the overlapping waveform (six pads) ranged from 67 ± 4% (at 18–49 J energy) to 99 ± 3% at ≥150 J; at comparable energies biphasic waveform shock success ranged from 26 ± 5% (p < 0.01 vs. encircling overlapping waveforms) to 99 ± 5% (p = NS). Damped sinusoidal waveform shock success ranged from 4 ± 1% (p < 0.01 vs. encircling overlapping waveform) to 73 ± 9% (p = NS). In the second experiment the three electrode pads, one capacitor encircling waveform achieved shock success rates comparable with the six-pad, three-capacitor waveform; at 18–49 J, success rates were 45 ± 15% versus 57 ± 12%, respectively (p = NS). At 100 J, success rates for both were 100%.

Conclusions. We conclude that encircling overlapping multipulse multipathway waveforms facilitate transthoracic defibrillation at low energies. These waveforms can be generated from a device that requires only three electrodes and one capacitor.     

Open chest defibrillation during cardiac surgery: Energy and current requirements

To define the optimal energy and current for open chest defibrillation of human hearts during cardiac surgery 202 patients were prospectively studied. First-shock delivered energies, determined by the date of surgery, were 5 joules (J) (55 patients), 10 J (87 patients) or 20 J (60 patients). Specially calibrated Datascope defibrillators, which displayed delivered energy and peak current, were used. The first shock resulted in defibrillation in 56 percent of patients receiving a shock of 5 J, 70 percent of patients receiving 10 J and 80 percent of patients receiving 20 J (p <0.01 versus 5 J). If necessary, shocks were repeated at the initial energy level; the success rates of initial plus repeated shocks at the same energy level were: 81 percent of patients receiving 5 J, 93 percent of patients receiving 10 J (p <0.05 versus 5 J) and 92 percent of patients receiving 20 J. Of the 55 patients who initially received a 5 J shock, with additional shocks at higher energy levels if necessary, the lowest current that successfully defibrillated the heart (that is, the threshold current) varied fourfold, ranging from 8 to 34 amperes (mean ± standard deviation 12 ± 5). One patient, who received the highest cumulative energy levels (503 J from 12 shocks, including four shocks of 75 J each), showed evidence of myocardial necrosis (positive technetium scan). Four others who received the next highest cumulative energy levels of 120 to 300 J from multiple shocks of up to 40 J had negative technetium scans. It is concluded that the optimal initial energy for open chest defibrillation is 10 to 20 J, and that this dose may be repeated if necessary. This dose will deflbrillate more than 90 percent of hearts, and is unlikely to cause shock-induced necrosis. Smaller doses (5 J) are less effective, whereas larger doses, especially if repeated many times, can cause myocardial necrosis.