2020 ESC Guidelines on acute coronary syndrome without ST-segment elevation : Recommendations and critical appraisal from the Dutch ACS and Interventional Cardiology working groups.

Recently, the European Society of Cardiology (ESC) has updated its guidelines for the management of patients with acute coronary syndrome (ACS) without ST-segment elevation. The current consensus document of the Dutch ACS working group and the Working Group of Interventional Cardiology of the Netherlands Society of Cardiology aims to put the 2020 ESC Guidelines into the Dutch perspective and to provide practical recommendations for Dutch cardiologists, focusing on antiplatelet therapy, risk assessment and criteria for invasive strategy.

Correction to: Guidelines for the management of myocardial infarction/injury with non-obstructive coronary arteries (MINOCA): a position paper from the Dutch ACS working group.

Correction to: Neth Heart J 2019 https://doi.org/10.1007/s12471-019-01344-6 The reference to the term acute coronary syndrome with normal or near-normal (non-obstructive) coronary arteries (ACSNNOCA) from Manolis et al. (2018) was inadvertently omitted to the original published article. Therefore, ….

Guidelines for the management of myocardial infarction/injury with non-obstructive coronary arteries (MINOCA): a position paper from the Dutch ACS working group.

Patients with myocardial infarction and non-obstructive coronary arteries (MINOCA), defined as angiographic stenosis <50%, represent a conundrum given the many potential underlying aetiologies. Possible causes of MINOCA can be subdivided into coronary, myocardial and non-cardiac disorders. MINOCA is found in up to 14% of patients presenting with an acute coronary syndrome. Clinical outcomes including mortality, and functional and psychosocial status, are comparable to those of patients with myocardial infarction and obstructive coronary arteries. However, many uncertainties remain regarding the definition, clinical features and management of these patients. This position paper of the Dutch ACS working group of the Netherlands Society of Cardiology aims to stress the importance of considering MINOCA as a dynamic working diagnosis and to guide the clinician in the management of patients with MINOCA by proposing a clinical diagnostic algorithm.

Timing of intervention in high-risk non-ST-elevation acute coronary syndromes in PCI versus non-PCI centres : Sub-group analysis of the ELISA-3 trial.

AIMS: To compare the effect of timing of intervention in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in percutaneous coronary intervention (PCI) versus non-PCI centres. METHODS AND RESULTS: A post-hoc sub-analysis was performed of the ELISA III trial, a randomised multicentre trial investigating outcome of early (< 12 h) versus late (> 48 h) angiography and revascularisation in 542 patients with high-risk NSTE-ACS. 90 patients were randomised in non-PCI centres and tended to benefit more from an early invasive strategy than patients included in the PCI centre (relative risk 0.23 vs. 0.85 [p for interaction = 0.089] for incidence of the combined primary endpoint of death, reinfarction and recurrent ischaemia after 30 days of follow-up). This was largely driven by reduction in recurrent ischaemia. In non-PCI centres, patients randomised to the late group had a 4 and 7 day longer period until PCI or coronary artery bypass grafting, respectively. This difference was less pronounced in the PCI centre. CONCLUSIONS: This post-hoc analysis from the ELISA-3 trial suggests that NSTE-ACS patients initially hospitalised in non-PCI centres show the largest benefit from early angiography and revascularisation, associated with a shorter waiting time to revascularisation. Improved patient logistics and transfer between non-PCI and PCI centres might therefore result in better clinical outcome.

Pentavalent human-bovine (WC3) reassortant rotavirus vaccine in special populations: a review of data from the Rotavirus Efficacy and Safety Trial.

Rotavirus gastroenteritis is a disease that causes significant morbidity and mortality worldwide in infants and children. The recent availability of efficacious rotavirus vaccines with favorable safety profiles has prompted medical agencies around the world to register the vaccines and countries and regions to recommend universal vaccination of healthy infants to prevent the serious health and economic consequences of rotavirus illness in children. Premature infants can be especially vulnerable to severe rotavirus infections, which may lead to serious outcomes. The clinical efficacy and safety of the pentavalent human-bovine rotavirus vaccine (PRV, RotaTeq, Merck, Whitehouse Station, NJ, USA) in healthy infants has been evaluated in the large phase III Rotavirus Efficacy and Safety Trial (REST). Preterm (N = 2,070) and exclusively breastfed infants (N = 1,566) were included in this study. The efficacy and safety of PRV in premature infants and in breastfed infants from the REST database are reviewed along with guidelines from national medical organizations for the use of PRV in these populations. Based on these data from the REST study, premature infants receive the same protection from PRV compared with nonpremature infants, without additional safety risk. Similarly, breastfed and nonbreastfed infants are equally protected from severe consequences of rotavirus gastroenteritis.

Administration of hepatitis A vaccine at 6 and 12 months of age concomitantly with hexavalent (DTaP-IPV-PRP approximately T-HBs) combination vaccine.

BACKGROUND: Administration of two doses of hepatitis A (HA) vaccine to children > or = 2 years of age has been shown to be protective. The present study assessed whether HA vaccine can be administered as early as 6 months of age and whether it can be administered concomitantly with a hexavalent (HV) vaccine at this age. METHODS: In an open label, randomized, parallel group study, the liquid HV vaccine (HEXAVAC) (diphtheria, tetanus, 2-component acellular pertussis, inactivated poliomyelitis vaccine, Haemophilus influenzae type b conjugated to tetanus protein and hepatitis B) was administered at 2, 4, 6, and 12 months of age to all children. HA vaccine (VAQTA) was given at 7 and 13 months in the separate administration group (Group 1) and at 6 and 12 months in the concomitant administration group (Group 2). Serum samples were obtained at 2, 7, 12, and 14 months in Group 1 and at 2, 7, 12, and 13 months in Group 2. The primary immunogenicity outcomes were the seroconversion rates for HA 1 month after the second dose of HA vaccine in initially seronegative subjects, and the seroconversion rates for each HV antigen 1 month after the third dose of the HV vaccine (both at 7 months of age). RESULTS: HA seropositivity rates 1 month after the second dose were 100% in both groups, regardless of initial serostatus. The responses to each HV antigen 1 month after the third dose were similar in both groups. The vaccines were generally well tolerated in both groups regardless of vaccine(s) administered. CONCLUSIONS: A schedule of two doses of HA vaccine, 6 months apart beginning at 6 months of age is highly immunogenic and well tolerated when administered alone or concomitantly with HV vaccine at 6 and 12 months of age.

[First facioscapulohumeral muscular dystrophy prenatal diagnosis in a Bulgarian family].

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common myopathy. It is characterized by progressive descendent involvement of facial, shoulder girdle, truncal and lower extremities muscles. FSHD locus was mapped on the terminal part of the long arm of chromosome 4 (4q35). The disease is caused by a deletion of an integral number of tandem D4Z4 repeats and dimension of the pathological fragments < or = 38kb. Prenatal diagnosis of FSHD is possible but it is potentially difficult because of the big amount and high quality of DNA required. Hereby we describe the first prenatal tests performed for a Bulgarian family.

Possible phenotypic dosage effect in patients compound heterozygous for FSHD-sized 4q35 alleles.

OBJECTIVE: Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) is associated with a contraction of the D4Z4 repeat array on chromosome 4. So far, homozygosity or compound heterozygosity for FSHD alleles has not been described, and it has been debated whether the absence of such subjects is because of the rarity or the lethality of the disorder. METHODS: Two unrelated families in which the probands are compound heterozygous for two FSHD-sized alleles were studied. Clinical examination, pulsed-field gel electrophoresis (PFGE) studies of DNA with probes proximal and distal to D4Z4, and cytogenetic analysis of metaphase chromosomes by FISH were performed. RESULTS: Complementary molecular and cytogenetic approaches confirmed the chromosome 4qA origin of all FSHD-sized repeat arrays that segregate in the families. CONCLUSIONS: Heterozygosity for FSHD-sized alleles is compatible with life in men and women. A possible dosage effect was observed in both probands in whom each 4qA allele contributed to the FSHD phenotype. Because at least one of the FSHD alleles in both families showed an unusual low penetrance, the authors propose that susceptibility for FSHD is partly determined by intrinsic properties of the disease allele other than the residual D4Z4 repeat size alone.

[Turkish children with recurrent abdominal pain and fever: familial Mediterranean fever]. / Turkse kinderen met recidiverende buikpijn en koorts: familiale mediterrane koorts.

Four children of Turkish origin, three boys aged 12, 8 and 7 years, and a girl aged 5 years, presented with clinical symptoms of familial Mediterranean fever. They had the characteristic episodes of fever combined with abdominal pain, thoracic pain, general malaise or arthralgia. Familial Mediterranean fever is an autosomal recessive genetic disorder restricted to people originating from the Middle East. The causative gene (MEFV) and many missense mutations have been identified. The clinical syndrome is characterised by self-limiting febrile episodes accompanied by inflammation of the serous membranes, resulting in peritonitis, pleuritis or synovitis. In untreated patients systemic amyloidosis may develop, which manifests as renal insufficiency. The diagnosis is based on the characteristic medical history and is confirmed by DNA analysis. Meanwhile, treatment with colchicine can be started. This is effective in 90% of affected patients. Being aware of the prevalence of familial Mediterranean fever in immigrant populations can improve the quality of life and prevent long-term complications.

Combining hepatitis A and B vaccination in children and adolescents.

Hepatitis A and B are common infections worldwide and their severity is related to the individual's age upon initial infection. Furthermore, when hepatitis B infection occurs in infants, the risk of becoming a chronic carrier is 90%. For hepatitis A, the lower incidence of disease arising from an improvement in living conditions leaves a greater number of children, adolescents and young adults susceptible to residual circulating virus. Consequently, initial infection occurs later in life when clinical illness is more frequent and the rate of morbidity and mortality higher. Although both viruses differ greatly, including their modes of transmission, the overlap in their epidemiology warrants the combination of hepatitis A and B vaccination. The immune response elicited by the combined hepatitis A and B vaccine following a three-dose schedule compares well with the anti-hepatitis A virus (HAV) and anti-hepatitis B sero-responses obtained with monovalent vaccines. In addition, it was shown that the seroprotection rate for anti-hepatitis B increased more rapidly with the administration of the combined vaccine, with values of more than 80% within 1 month after the first two doses (schedule, 0, 1 and 6 months). Currently, according to the World Health Organization recommendations, more than 116 countries are vaccinating their infants and/or adolescents against hepatitis B. Recently, several countries were considering or have decided to begin mass vaccination against HAV (more than fifteen states in the US, Spain (Catalonia), Italy (Puglia)). For these countries, the combination of hepatitis A and B antigens in one single vaccine offers the following advantages: fewer injections for protection against two infections, better compliance, lower implementation costs, and fewer missed vaccination opportunities. Further simplification of the schedule, by reducing the number of doses, would improve the compliance rate as well as being more convenient for the vaccinee. This should translate into a reduction in costs associated with vaccine administration. In some recent vaccine studies, the immunogenicity and safety profile of a two-dose schedule (0 and 6 months) of the adult formulation of the combined hepatitis A and B vaccine was investigated in children aged 1-11 years, as well as in adolescents aged 12-15 years. Current results indicate that this two-dose schedule of the adult formulation could be considered a viable alternative for immunization of children and adolescents.

Complete allele information in the diagnosis of facioscapulohumeral muscular dystrophy by triple DNA analysis.

Facioscapulohumeral muscular dystrophy is caused by partial deletion of the D4Z4 repeat array on chromosome 4q35. Genetic diagnosis is based on sizing of this repeat array, which is complicated by cross-hybridization of a homologous polymorphic repeat array on chromosome 10 and by the frequent exchanges between these chromosomal regions. The restriction enzyme XapI optimizes the diagnosis of facioscapulohumeral muscular dystrophy by uniquely digesting 4-derived repeat units and leaving 10-derived repeat units undigested, thus complementing BlnI, which uniquely digests 10-derived repeat units. A triple analysis with EcoRI, EcoRI/BlnI, and XapI unequivocally allows characterization of each of the four alleles, whether homogeneous or hybrid. This is particularly useful in the case of identical sized 4-derived and 10-derived arrays, in situations of suspected facioscapulohumeral muscular dystrophy with nonstandard allele configurations, and for assignment of hybrid fragments to their original alleles.

A two dose schedule for combined hepatitis A and hepatitis B vaccination in children ages one to eleven years.

RATIONALE: A combined hepatitis A and B vaccine, Twinrix, containing at least 720 enzyme-linked immunosorbent assay units of hepatitis A antigen and 20 microg of hepatitis B antigen in the adult formulation and half those doses in the pediatric formulation, has been available in many countries since 1997. This vaccine is administered on a three dose schedule: 0, 1 and 6 months. A reduction in the number of doses would add convenience for the vaccinees and reduce administration-associated costs. We investigated the safety and immunogenicity profile of the adult formulation administered at 0 and 6 months in children ages 1 to 11 years. METHODS: A total of 237 children of both sexes were enrolled. Blood sampling was performed at 0 and 1, 2, 6 and 7 months. Seropositivity for anti-hepatitis A virus was defined as > or = 33 mIU/ml and seroprotection against hepatitis B virus as > or =10 mIU/ml. Data on solicited and unsolicited adverse events were collected on diary cards. RESULTS: The vaccine was well-tolerated in all subjects. At Month 7 all subjects had seroconverted for anti-hepatitis A virus antibodies with a high geometric mean concentration (11 543 mIU/ml). We observed a continuous increase in anti-hepatitis B surface antibody (anti-HBs) seroconversion rates and seroprotection rates until Month 6. After the second dose (Month 7), all subjects seroconverted for anti-HBs antibodies with a high geometric mean concentration (8056 mIU/ml) and 98.5% of the subjects were considered seroprotected. CONCLUSION: The two dose adult formulation could be an alternative to prevent hepatitis A and hepatitis B infection in children ages 1 to 11 years.

A randomised controlled trial with a diphtheria-tetanus-acellular pertussis (dTpa) vaccine in adults.

The aim of this assessor-blinded trial was to compare the immunogenicity and reactogenicity of a candidate diphtheria, tetanus toxoids and acellular pertussis vaccine with reduced antigen content for diphtheria and pertussis (dTpa) with a licensed reduced adult-type diphtheria-tetanus vaccine Td (reduced diphtheria content) and with an experimental candidate monovalent acellular pertussis vaccine with reduced antigen content (pa). The dTpa and pa vaccines had identical pertussis antigen content. A total of 299 healthy adults (> or =18 years, mean age: 30.1 years+/-10.7) were randomised into 3 groups to receive a single dose of one of the study vaccines. In all groups, clinically significant reactions (severe) were infrequent (0-6%) and no serious adverse events were reported during the study. The incidence of local and systemic reactions following the administration of dTpa was comparable to the Td vaccine group. Of the total study group, prior to vaccination 52. 3 and 93.2% of the subjects had anti-diphtheria and anti-tetanus antibody levels > or = 0.1 IU/ml, respectively; and 73.1, 98.2 and 74.5% of the subjects were seropositive for pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) antibodies, respectively. One month after vaccination, a similar percentage of subjects in the dTpa and Td groups had anti-diphtheria (88.4% vs 90. 1%) and anti-tetanus (100% vs 98.9%) antibody levels > or =0.1 IU/ml. Similar anti-FHA (100%) and anti-PRN (98.9%) vaccine response rates were seen in the dTpa and pa groups, while the anti-PT vaccine response rates were 96.8 and 100.0%, respectively. The dTpa vaccine is as well tolerated and immunogenic as the licensed Td vaccine, and additionally, can also boost antibodies against pertussis.

De novo facioscapulohumeral muscular dystrophy: frequent somatic mosaicism, sex-dependent phenotype, and the role of mitotic transchromosomal repeat interaction between chromosomes 4 and 10.

Autosomal dominant facioscapulohumeral muscular dystrophy (FSHD) is caused by deletion of most copies of the 3.3-kb subtelomeric D4Z4 repeat array on chromosome 4q. The molecular mechanisms behind the deletion and the high proportion of new mutations have remained elusive. We surveyed 35 de novo FSHD families and found somatic mosaicism in 40% of cases, in either the patient or an asymptomatic parent. Mosaic males were typically affected; mosaic females were more often the unaffected parent of a nonmosaic de novo patient. A genotypic-severity score, composed of the residual repeat size and the degree of somatic mosaicism, yields a consistent relationship with severity and age at onset of disease. Mosaic females had a higher proportion of somatic mosaicism than did mosaic males. The repeat deletion is significantly enhanced by supernumerary homologous repeat arrays. In 10% of normal chromosomes, 4-type repeat arrays are present on chromosome 10. In mosaic individuals, 4-type repeats on chromosome 10 are almost five times more frequent. The reverse configuration, also 10% in normal chromosomes, was not found, indicating that mutations may arise from transchromosomal interaction, to which the increase in 4-type repeat clusters is a predisposing factor. The somatic mosaicism suggests a mainly mitotic origin; mitotic interchromosomal gene conversion or translocation between fully homologous 4-type repeat arrays may be a major mechanism for FSHD mutations.

A new dosage test for subtelomeric 4;10 translocations improves conventional diagnosis of facioscapulohumeral muscular dystrophy (FSHD).

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the size reduction of a polymorphic repeat array on 4q35. Probe p13E-11 recognises this chromosomal rearrangement and is generally used for diagnosis. However, diagnosis of FSHD is complicated by three factors. First, the probe cross hybridises to a highly homologous repeat array locus on chromosome 10q26. Second, although a BlnI polymorphism allows discrimination between the repeat units on chromosomes 4 and 10 and greatly facilitates FSHD diagnosis, the occurrence of translocations between chromosomes 4 and 10 further complicates accurate FSHD diagnosis. Third, the recent identification of deletions of p13E-11 in both control and FSHD populations is an additional complicating factor. Although pulsed field gel electrophoresis is very useful and sometimes necessary to detect these rearrangements, this technique is not operational in most FSHD diagnostic laboratories. Moreover, repeat arrays >200 kb are often difficult to detect and can falsely suggest a deletion of p13E-11. Therefore, we have developed an easy and reliable Southern blotting method to identify exchanges between 4 type and 10 type repeat arrays and deletions of p13E-11. This BglII-BlnI dosage test addresses all the above mentioned complicating factors and can be carried out in addition to the standard Southern blot analysis for FSHD diagnosis as performed in most laboratories. It will enhance the specificity and sensitivity of conventional FSHD diagnosis to the values obtained by PFGE based diagnosis of FSHD. Moreover, this study delimits the FSHD candidate gene region by mapping the 4;10 translocation breakpoint proximal to the polymorphic BlnI site in the first repeat unit.

Growth of a single-domain smectic phase in a thin liquid-crystalline polymer film.

The ordering process and kinetics in thin films (200-800-nm thick) of a thermotropic side-chain liquid-crystalline polymer have been investigated vertically and laterally, respectively, by x-ray reflectivity and atomic-force microscopy. The original smooth and amorphous spin-coated films initially become corrugated upon annealing in the smectic mesophase. The roughening of the surface results from the formation of randomly oriented microcrystalline domains in the film. At the same time, however, a laterally macroscopic crystal starts to grow from the substrate surface in the direction of the polymer-air interface at the expense of these domain structures. Finally, a nicely ordered single crystal with parallel-ordered bilayers is formed in the film as well as at the polymer-air interface. This one-dimensional crystallization, actually recrystallization, depends strongly on the temperature due to viscosity effects. At low temperatures, just above the glass-transition temperature, the ordering is very slow, but with increasing temperature the crystal growth is faster. An Arrhenius-type plot gives an activation energy of 122 kJ/mol, which we ascribe to the expected reorientations of the mesogenic groups during the recrystallization process.

Inter- and intrachromosomal sub-telomeric rearrangements on 4q35: implications for facioscapulohumeral muscular dystrophy (FSHD) aetiology and diagnosis.

The autosomal dominant myopathy facioscapulohumeral muscular dystrophy (FSHD) is causally related to a short Eco RI fragment detected by probe p13E-11. This remnant fragment is the result of a deletion of an integral number of tandemly arrayed 3.3 kb repeat units (D4Z4) on 4q35. Despite intensive efforts, no transcribed sequences have been identified within this array. Previously, we have shown that these repeats on 4q35 have been exchanged for a similar highly homologous repeat locus on 10q26 in 20% of the population and that a short chromosome 10-like array on 4q35 also results in FSHD. Here, we describe the hybrid structure of some of these repeat arrays, reflecting additional sub-telomeric instability. In three healthy individuals carrying a 4-like repeat on chromosome 10 or vice versa, one repeat array was shown to consist of hybrid clusters of 4-derived and 10-derived repeat units. Moreover, employing pulsed field gel electrophoresis analysis, we identified two unrelated individuals carrying deletions of a chromosomal segment (p13E-11) proximal to the repeat locus. These deletions were not associated with FSHD. In one of these cases, however, an expansion of the deletion into the repeat array was observed in one of his children suffering from FSHD. These data provide additional evidence for instability of this sub-telomeric region and suggests that the length of the repeat, and not its intrinsic properties, is crucial to FSHD. Moreover, they are in agreement with the hypothesis that FSHD is caused by a position effect in which the repeat structure influences the expression of genes nearby. Therefore, the region deleted proximal to the repeat locus in healthy individuals can be instrumental to refine the critical region for FSHD1.