Next generation phenotyping in Emanuel and Pallister-Killian syndrome using computer-aided facial dysmorphology analysis of 2D photos.

High throughput approaches are continuously progressing and have become a major part of clinical diagnostics. Still, the critical process of detailed phenotyping and gathering clinical information has not changed much in the last decades. Forms of next generation phenotyping (NGP) are needed to increase further the value of any kind of genetic approaches, including timely consideration of (molecular) cytogenetics during the diagnostic quest. As NGP we used in this study the facial dysmorphology novel analysis (FDNA) technology to automatically identify facial phenotypes associated with Emanuel (ES) and Pallister-Killian Syndrome (PKS) from 2D facial photos. The comparison between ES or PKS and normal individuals expressed a full separation between the cohorts. Our results show that NPG is able to help in the clinic, and could reduce the time patients spend in diagnostic odyssey. It also helps to differentiate ES or PKS from each other and other patients with small supernumerary marker chromosomes, especially in countries with no access to more sophisticated genetic approaches apart from banding cytogenetics. Inclusion of more facial pictures of patient with sSMC, like isochromosome-18p-, cat-eye-syndrome or others may contribute to higher detection rates in future.

Is the duration of dual antiplatelet therapy (DAPT) excessive in post-angioplasty in chronic coronary syndrome? Data from the France-PCI registry (2014-2019).

Background: while the duration of dual antiplatelet therapy (DAPT) following coronary angioplasty for chronic coronary syndrome (CCS) recommended by the European Society of Cardiology has decreased over the last decade, little is known about the adherence to those guidelines in clinical practice in France. Aim: To analyze the real duration of DAPT post coronary angioplasty in CCS, as well as the factors affecting this duration. Methods: Between 2014 and 2019, 8.836 percutaneous coronary interventions for CCS from the France-PCI registry were evaluated, with 1 year follow up, after exclusion of patients receiving oral anticoagulants, procedures performed within one year of an acute coronary syndrome, and repeat angioplasty. Results: Post-percutaneous coronary intervention (PCI) DAPT duration was > 12 months for 53.1% of patients treated for CCS; 30.5% had a DAPT between 7 and 12 months, and 16.4% a DAPT ≤ 6 months. Patients with L-DAPT (>12 months) were at higher ischemic risk [25.0% of DAPT score ≥2 vs. 18.8% DAPT score ≥2 in S&I-DAPT group (≤12 months)]. The most commonly used P2Y12 inhibitor was clopidogrel (82.2%). The prescription of ticagrelor increased over the period. Conclusions: post-PCI DAPT duration in CCS was higher than international recommendations in the France PCI registry between 2014 and 2019. More than half of the angioplasty performed for CCS are followed by a DAPT > 12 months. Ischemic risk assessment influences the duration of DAPT. This risk is probably overestimated nowadays, leading to a prolongation of DAPT beyond the recommended durations, thus increasing the bleeding risk.

[stent thrombosis : A won battle ? (data from the France PCI registry)]. / Thrombose de stent : une bataille gagnée ? (Données du registre France PCI).

GOAL: The aim of the study is to assess the incidence, risk factors and prognosis of definite stent thrombosis (ST) at 1 year in the France PCI multicenter prospective registry. PATIENTS AND METHODS: Only patients who underwent coronary angioplasty with at least one stent implantation between 1st January 2014 and 31 December 2019 were included. The population was separated into 2 groups: the "ST" group with stent thrombosis and the "control" group without stent thrombosis. RESULTS: 35,435 patients were included. 256 patients (0.72%) presented a ST at 1 year. The rate of ST decreased significantly in acute coronary syndrome (1.5% in 2014 vs. 0.73% in 2019; p = 0.05) but not in chronic coronary syndrome (0.46% in 2014 vs 0.40%; p = 0.98). The risk factors are young age (65.8 years vs 68.2; p = 0.002), clinical context (35.27% vs 16.68%; p = 0.0001), diabetes (35.2 % vs 26.4%; p = 0.002), renal failure (11.7% vs 8%; p = 0.009) and history of coronary angioplasty (28.63% vs 21.86%; p = 0.009) and peripheral arterial disease (14.5% vs 10.1%; p = 0.021), LV dysfunction (37% vs 27.5%; p = 0.003), mean length (39.6 mm vs 31, 7mm; p <0.0001) and the mean number of stents per procedure (1.9 vs 1.6; p <0.0001), a TIMI flow ≤1 pre procedure (21.5% vs 12.4%; p <0.0001) and an intrastent restenosis (11% vs 6%; p <0.0001). The 1-year mortality of the ST group was significantly higher than that of the control group (19.14% vs 5.82%; p <0.0001). CONCLUSION: Since 2014, the incidence of ST at 1 year has been decreasing but remains stuck at a floor level of 0.54% in 2019. The battle for ST seems to have been partly won and its risk factors well identified, but its mortality is still high.

Quality criteria for cardiac images: an update.

The DIMOND II and III Cardiology Groups have agreed on quality criteria for cardiac images and developed a scoring system, to provide a tool to test quality of coronary angiograms, which was demonstrated to be of value in clinical practice. In the last years, digital flat panel technology has been introduced in cardiac angiographic systems and the radiological technique may have been influenced by the better performance of these new detectors. This advance in digital imaging, together with the lesson learned from previous studies, warranted the revision of the quality criteria for cardiac angiographic images as formerly defined. DIMOND criteria were reassessed to allow a simpler evaluation of angiograms. Clinical criteria were simplified and separated from technical criteria. Furthermore, the characteristics of an optimised angiographic technique have been outlined.

[The potential of magnetic resonance imaging for the surveillance of septal alcohol ablation in hypertrophic obstructive cardiomyopathy. A case report]. / Potentialité de l'imagerie par résonance magnétique pour la surveillance du traitement par alcoolisation septale de la cardiopathie hypertrophique obstructive. A propos d'un cas.

We describe here the MRI surveillance of septal alcohol ablation in a case of symptomatic obstructive cardiomyopathy. MRI examinations were performed before, 15 days and 2 months after alcohol ablation using an identical protocol to study the function, regional perfusion and the equilibrium perfusion in order to directly visualize the infarction. MRI seems to be an excellent investigation in the surveillance of such patients, allowing precise quantification of the infarcted zone. The various stages of cellular necrosis in the induced infarct were demonstrated, and the role of remodelling in increasing the functional area of the systolic ejection pathway.

Effect of vanadate on the activity of rat jejunal 6-phosphofructo-1-kinase.

The effect of sodium orthovanadate on the activity of 6-phosphofructo-1-kinase (PFK) in the epithelial cells of rat small intestine was investigated. Injection of vanadate (2.5 mg/rat) into rats at 2-day intervals per week for two consecutive weeks resulted in a significant decrease in the maximal activities and activity ratios (activity at 0.5 mM fructose-6-phosphate at pH 7.0/activity at pH 8.0 [v0.5/V]) of the partially purified PFK in rat jejunum. Also, the sensitivity of jejunal PFK to inhibition by ATP increased in rats treated with vanadate. The addition of 1 microM fructose-2,6-biphosphate and 50 microM AMP in the assays released the enzyme inhibition by ATP, and no significant difference was seen between vanadate-injected and control rats. Moreover, the extent of activation with 1 microM fructose-2,6-bisphosphate was significantly higher (79%) in vanadate-injected rats than in control rats (26%). The present results indicate that rat jejunal PFK is highly inhibited with vanadate in vivo. Therefore, although vanadate has been considered to be an insulin-like agent, because of its insulin-like effects on adipocytes and skeletal muscle, the present results may indicate that this behavior could not be applicable to normal rat tissues, because the effect of vanadate on jejunal PFK is clearly opposite that of insulin.

[Percutaneous aortic valvuloplasty. Long-term outcome apropos of 85 patients with successful dilatation]. / Valvuloplastie aortique percutanée. Evolution à long terme à propos de 85 patients dilatés avec succès.

The outcome at 2, 6, 12, 18 and 24 months in terms of clinical status and Doppler echocardiographic parameters of 85 patients successfully dilated out of 116 patients undergoing percutaneous aortic valvuloplasty is reported. The objectives were to determine the survival rate, degree of clinical remission, the restenosis rate and its predictive factors. The 31 patients considered to be primary failures were excluded from the study. The global survival rates were 90 +/- 2% at 2 months, 84 +/- 4% at 6 months, 78 +/- 5% at 12 months, 69 +/- 6% at 18 months and 60 +/- 8% at 2 years. Patients in clinical remission and with clinical relapse were compared at the 6th month: relapse was significantly, related to prevalvuloplathy, low cardiac output (p = 0.05), low ejection fraction (p less than 0.03) and low fractional shortening (p less than 0.01), but the clinical relapse was independent of aortic valve surface area before and dilatation. In the relapse group, 14 patients (12%) were operated without complications in the first month of follow up, 6 patients underwent repeat valvuloplasty with 4 immediate failures and 2 improvements. The other patients were treated medically. The restenosis rate (loss of greater than 50% of initial gain in surface area or return of pre-valvuloplasty maximal pressure gradient +/- 25%) increased up to the 12th month in both groups (remission and relapse) and reached 78% at 12 +/- 3 months and seemed more pronounced in the less severe aortic stenosis. The incidence of restenosis was independent of gain in surface area after valvuloplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Psychological adjustment of adoptive parents-to-be.

Adjustment and functioning of adoptive parents-to-be were examined during the last stage of expectancy, focusing on possible antecedents or determinants of successful parenting. Results failed to support expectations of short-term adverse effects from transitional stresses, and suggested that the expectancy period may not be equivalent for adoptive and biological parents, especially for mothers. Programmatic implications are discussed.

Main clinical, therapeutic and technical factors related to patient's maximum skin dose in interventional cardiology procedures.

OBJECTIVE: The study aimed to characterise the factors related to the X-ray dose delivered to the patient's skin during interventional cardiology procedures. METHODS: We studied 177 coronary angiographies (CAs) and/or percutaneous transluminal coronary angioplasties (PTCAs) carried out in a French clinic on the same radiography table. The clinical and therapeutic characteristics, and the technical parameters of the procedures, were collected. The dose area product (DAP) and the maximum skin dose (MSD) were measured by an ionisation chamber (Diamentor; Philips, Amsterdam, The Netherlands) and radiosensitive film (Gafchromic; International Specialty Products Advanced Materials Group, Wayne, NJ). Multivariate analyses were used to assess the effects of the factors of interest on dose. RESULTS: The mean MSD and DAP were respectively 389 mGy and 65 Gy cm(-2) for CAs, and 916 mGy and 69 Gy cm(-2) for PTCAs. For 8% of the procedures, the MSD exceeded 2 Gy. Although a linear relationship between the MSD and the DAP was observed for CAs (r=0.93), a simple extrapolation of such a model to PTCAs would lead to an inadequate assessment of the risk, especially for the highest dose values. For PTCAs, the body mass index, the therapeutic complexity, the fluoroscopy time and the number of cine frames were independent explanatory factors of the MSD, whoever the practitioner was. Moreover, the effect of technical factors such as collimation, cinematography settings and X-ray tube orientations on the DAP was shown. CONCLUSION: Optimising the technical options for interventional procedures and training staff on radiation protection might notably reduce the dose and ultimately avoid patient skin lesions.

[Iatrogenic dissection of the right coronary artery and the ascending aorta during coronary intervention]. / Dissection iatrogène de la coronaire droite et de l'aorte ascendante au cours d'une procédure d'angioplastie.

Iatrogenic acute dissection of the ascending aorta following coronary angiography and percutaneous intervention is rare. The options for treatment are dictated by patient stability, nature of dissection of the coronary vessel, ability to restore the coronary circulation and extent of aortic dissection. Usually localized aortic dissections have been managed conservatively or treated by sealing the entry with a coronary stent. Extensive dissections may require a surgical intervention. We report the case of a 52-year-old man with iatrogenic dissection of the right coronary artery ostium and extension of the dissection to the ascending aorta during intraluminal angioplasty of an obstructive lesion in the first portion of the right coronary artery. The patient was managed conservatively without stenting (failure stenting of the right coronary artery) and without surgery. Aortic dissection was monitored by means of transesophageal echocardiography. Serial computed tomography scans demonstrated spontaneous resolution of the dissection. The evolution of the patient was satisfactory. Causes, frequency and treatment procedures of this iatrogeny are discussed.

[Comorbidity of mental and internal medical disorders in inpatients treated at the clinic for technical orthopedics]. / Komorbidität psychischer und internistischer Erkrankungen bei stationär behandelten Patienten in der technischen Orthopädie.

Due to the severity of their clinical picture and their shattered sense of physical inviolability that almost always is associated with their condition as well as their changed physical appearance, inpatients being treated at the clinic for technical orthopedics frequently exhibit comorbid mental disorders. This article examines these mental health comorbidities. The proportion of adjustment disorders in this group was shown to be noticeably higher than in a comparative group of outpatients attending a psychosomatic/psychotherapeutic clinic. Furthermore, diabetes mellitus proved to be another statistically significant organic comorbidity in the patients treated at the clinic for technical orthopedics. This article discusses the extent to which the chronicity of this disease affects the psychosomatic diagnoses but also the course of the treatment in the clinic for technical orthopedics. In conclusion, this article emphasizes the need for close interdisciplinary management for this highly selected patient group because of the high rates of comorbidity.

D-alanine: D-alanine ligase of Escherichia coli. Expression, purification and inhibitory studies on the cloned enzyme.

A 1.2 kb BamHI fragment from pDK30 [Robinson, Kenan, Sweeney & Donachie (1986) J. Bacteriol. 167, 809-817] was cloned in pDOC55 [O'Connor & Timmis (1987) J. Bacteriol. 169, 4457-4482] to give two constructs, pDOC89 and pDOC87, in which the Escherichia coli D-alanine:D-alanine ligase (EC 6.3.2.4) gene (ddl) was placed under the control of the lac and lambda PL promoters respectively. Both constructs, when used to transform E. coli M72, gave similar levels of expression of the ddl gene. The expressed enzyme was purified to homogeneity and the amino acid sequence of its N-terminal region was found to be consistent with that predicted from the gene sequence, except that the N-terminal methionine was not present in the mature protein. [1(S)-Aminoethyl][(2RS)2-carboxy-1-octyl]phosphinic acid (I), previously shown to bind tightly to Enterococcus faecalis and Salmonella typhimurium D-alanine:D-alanine ligases following phosphorylation Parsons, Patchett, Bull, Schoen, Taub, Davidson, Combs, Springer, Gadebusch, Weissberger, Valiant, Mellin & Busch (1988) J. Med. Chem. 31, 1772-1778; Duncan & Walsh (1988) Biochemistry 27, 3709-3714], was found to be a classical slow-binding inhibitor of the E. coli ligase.

Percutaneous transluminal angioplasty of radial artery grafts.

The radial artery is being used with increasing frequency to replace the saphenous vein as a coronary artery bypass graft, in the belief that it will provide improved long-term patency. Several centers have confirmed that the early results of surgery using the radial artery seem to be better than those obtained with saphenous grafts. Despite these apparent gains, early failure of the radial artery graft can occur and is frequently associated with symptomatic myocardial ischemia. Percutaneous angioplasty is an alternative to reoperation to treat lesions occurring on radial artery grafts. We report on 4 patients who underwent angioplasty of radial artery grafts.

Randomised comparison of coronary stenting with and without balloon predilatation in selected patients.

BACKGROUND: The SWIBAP (stent without balloon predilatation) prospective randomised trial was designed to compare direct coronary stenting with stenting preceded by lesion predilatation with an angioplasty balloon. OBJECTIVE: To determine the feasibility and safety of direct stenting in non-complex coronary lesions in a prospective study. PATIENTS AND DESIGN: All patients < 76 years of age scheduled to undergo angioplasty of a non-complex, non-calcified lesion in a coronary artery of > 3.0 mm, who granted their informed consent, were randomised into the trial. In group I, the stent was placed without balloon predilatation, while in group II stent implantation was preceded by balloon predilatation. The primary end point was the angiographic result according to procedure assigned by randomisation. An intravascular ultrasound substudy was performed in 60 patients. RESULTS: Stent implantation was successful without predilatation in 192 of the 197 group I patients (97.5%), and with predilatation in 197 of the 199 group II patients (99%) (NS). No in-hospital stent thrombosis or death occurred. Overall procedural times, fluoroscopy times, and volumes of contrast agent given (mean (SD)) in group I v group II were 23.50 (13.54) min v 27.96 (15.23) min (p = 0.002), 6.04 (4.13) min v 6.67 (3.65) min (NS), and 135 (65) ml v 157 (62) ml (p < 0.001), respectively. No major adverse cardiovascular events had occurred by 30 days. CONCLUSIONS: The feasibility and safety of direct stenting of selected and non-complex coronary lesions is confirmed. This technique was as successful as the conventional approach and was associated with a minor reduction in fluoroscopic exposure and procedure time and the administration of less contrast agent.