Reasons for rejection of rhinoplasty seeking patients: a multicentre observational study.

BACKGROUND: To date, research on preoperative patient selection has mainly focused on patient personality, with body dysmorphic disorder (BDD) being the most studied. Despite the many reasons for not planning a rhinoplasty, no data are available on the nature of these reasons. Our aim is to conduct a multicentre international observational study on the reasons for rejection of patients seeking rhinoplasty in 5 tertiary rhinoplasty care centres. METHODS: Surgeons documented the reasons for not scheduling a rhinoplasty in consecutive patients who consulted them between January 2021 and March 2022 using a predefined list of reasons for rejection. Surgeons were also asked to report on the patient attitudes after rejection, and about the advice given to patients in the event of refusal. RESULTS: 186 patients seeking rhinoplasty were included. Multiple reasons for rejection were present in 76% of patients, with a mean of 2.9 reasons for rejection per patient. Overall, patient-related factors were most frequently associated with rejection (64.3%), followed by nose-related factors (28.4%), surgeon-related factors (6.0 %) and surgery-related factors (1.3%). The presence of severe BDD symptoms was reported in only 11.3% of the rejected patients. Patients rejected for rhinoplasty were advised to reconsider the surgery (32.8 %) and/or were referred to another surgeon (32.8%). No further action was taken in 39.8% of the patients. Of the patients who were rejected, most had a neutral (39.2 %) or positive (37.1 %) attitude in relation to the lack of rhinoplasty planning. CONCLUSION: This study highlights the variety of reasons for which patients seeking rhinoplasty are not considered good candidates for a rhinoplasty, with patient-related factors being more prevalent than nose-related and other factors. Increasing awareness on the impact of adequate patient selection for rhinoplasty may contribute to better outcomes in rhinoplasty.

EUFOREA Rhinology Research Forum 2016: report of the brainstorming sessions on needs and priorities in rhinitis and rhinosinusitis.

The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016.

Repeat to gene expression ratios in leukemic blast cells can stratify risk prediction in acute myeloid leukemia.

BACKGROUND: Repeat elements constitute a large proportion of the human genome and recent evidence indicates that repeat element expression has functional roles in both physiological and pathological states. Specifically for cancer, transcription of endogenous retrotransposons is often suppressed to attenuate an anti-tumor immune response, whereas aberrant expression of heterochromatin-derived satellite RNA has been identified as a tumor driver. These insights demonstrate separate functions for the dysregulation of distinct repeat subclasses in either the attenuation or progression of human solid tumors. For hematopoietic malignancies, such as Acute Myeloid Leukemia (AML), only very few studies on the expression/dysregulation of repeat elements were done. METHODS: To study the expression of repeat elements in AML, we performed total-RNA sequencing of healthy CD34 + cells and of leukemic blast cells from primary AML patient material. We also developed an integrative bioinformatic approach that can quantify the expression of repeat transcripts from all repeat subclasses (SINE/ALU, LINE, ERV and satellites) in relation to the expression of gene and other non-repeat transcripts (i.e. R/G ratio). This novel approach can be used as an instructive signature for repeat element expression and has been extended to the analysis of poly(A)-RNA sequencing datasets from Blueprint and TCGA consortia that together comprise 120 AML patient samples. RESULTS: We identified that repeat element expression is generally down-regulated during hematopoietic differentiation and that relative changes in repeat to gene expression can stratify risk prediction of AML patients and correlate with overall survival probabilities. A high R/G ratio identifies AML patient subgroups with a favorable prognosis, whereas a low R/G ratio is prevalent in AML patient subgroups with a poor prognosis. CONCLUSIONS: We developed an integrative bioinformatic approach that defines a general model for the analysis of repeat element dysregulation in physiological and pathological development. We find that changes in repeat to gene expression (i.e. R/G ratios) correlate with hematopoietic differentiation and can sub-stratify AML patients into low-risk and high-risk subgroups. Thus, the definition of a R/G ratio can serve as a valuable biomarker for AML and could also provide insights into differential patient response to epigenetic drug treatment.

Brain abscess caused by paradoxical embolization in Ebstein's anomaly.

A 25-year-old woman presented with Streptococcus milleri brain abscess. Previous cardiac history was unremarkable. In search for a source of embolism echocardiography was performed and revealed a previous undiagnosed Ebstein's anomaly of moderate severity with apical displacement of the septal leaflet of the tricuspid valve and a secundum atrial septal defect (ASD) with left to right shunt. The combination of increased right atrial pressure caused by Ebstein's and an ASD with possibility of transient right to left shunt predispose for paradoxical embolization. The most likely reason for development of a brain abscess in this patient is septic embolization from an infectious focus outside the heart. Ebstein's anomaly can remain undiagnosed until adulthood if the right ventricle, in spite of the smaller size, is haemodynamically well functioning.

Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy.

Three novel beta cardiac myosin heavy chain (MHC) gene missense mutations, Phe513Cys, Gly716Arg, and Arg719Trp, which cause familial hypertrophic cardiomyopathy (FHC) are described. One mutation in exon 15 (Phe513Cys) does not alter the charge of the encoded amino acid, and affected family members have a near normal life expectancy. The Gly716Arg mutation (exon 19; charge change of +1) causes FHC in three family members, one of whom underwent transplantation for heart failure. The Arg719Trp mutation (exon 19; charge change of -1) was found in four unrelated FHC families with a high incidence of premature death and an average life expectancy in affected individuals of 38 yr. A comparable high frequency of disease-related deaths in four families with the Arg719Trp mutation suggests that this specific gene defect directly accounts for the observed malignant phenotype. Further, the significantly different life expectancies associated with the Arg719Trp vs. Phe513Cys mutation (P < 0.001) support the hypothesis that mutations which alter the charge of the encoded amino acid affect survival more significantly than those that produce a conservative amino acid change.

Successful treatment of severe heart failure in an infant with Hurler syndrome.

Hurler syndrome (MPS IH) is the most severe form of mucopolysaccharidosis type I. It is caused by deficiency or absence of the enzyme alpha-L-iduronidase. Cardiac involvement includes cardiomyopathy and valve and coronary pathology. Cardiomyopathy causing symptoms in an infant with MPS IH carries a very poor prognosis. We describe a previously healthy 10-week-old boy who was admitted to hospital critically ill with severe heart failure. Echocardiography on admission showed severe dilatation of the left ventricle and moderate insufficiency of the left-sided cardiac valves. Accumulation of heparan sulfate and dermatan sulfate substrates in the urine and leukocyte analysis confirmed the diagnosis of MPS IH. Enzyme replacement therapy (ERT) with intravenous laronidase at a standard dosage of 100 U/kg weekly was started soon after. This improved the child's general clinical wellbeing dramatically. His cardiac function improved steadily over a period of months. Stem cell transplantation from cord blood is not available in Norway and he underwent successful transplantation from an unrelated bone marrow donor at the age of 11 months. ERT was stopped four months later. At the age of 26 months his heart function is close to normal and he is currently on no medication. This report highlights three important clinical issues: (1) MPS IH must be considered in infants with cardiomyopathy; (2) early ERT may have a significant impact on short-term outcome in children less than 18 months old with severe cardiomyopathy; (3) our report confirms that patients in poor condition benefit from ERT before stem cell transplantation.

Algal-bacterial interactions in metal contaminated floodplain sediments.

The aim of the present study was to investigate algal-bacterial interactions in a gradient of metal contaminated natural sediments. By means of multivariate techniques, we related the genetic structure (denaturing gradient gel electrophoresis, DGGE) and the physiological structure (community-level physiological profiling, CLPP) of the bacterial communities to the species composition of the algal communities and to the abiotic environmental variables, including metal contamination. The results revealed that genetic and physiological structure of the bacterial communities correlated with the species composition of the algal community, but hardly to the level of metal pollution. This must be interpreted as an indication for a strong and species-specific linkage of algal and bacterial species in floodplain sediments. Metals were, however, not proven to affect either the algal or the bacterial communities of the Dutch river floodplains.

Mid-childhood outcomes after pre-viable preterm premature rupture of membranes.

OBJECTIVES: Investigate cardiorespiratory outcomes in children surviving previable preterm premature rupture of membranes (PV-PPROM) before 22 weeks' gestational age (GA) with minimum 2 weeks latency. STUDY DESIGN: Single institution, follow-up of retrospectively identified children who were born after PV-PPROM during 2000-2004, and individually matched preterm-born controls. RESULTS: Eleven PV-PPROM and matched control children were included at mean age of 10.5 and 10.7 years. Rupture of membranes occurred at mean GA 182 and 276 weeks and birth at 283 and 286 weeks, respectively. Compared to controls, the PV-PPROM group had significantly poorer lung function, findings on echocardiography indicating mild pulmonary hypertension, and lower peak oxygen consumption. Chart reviews suggested more motor difficulties and a tendency towards more problems with learning and attention. CONCLUSION: The findings highlight a preterm-born sub-group in need of targeted long-term monitoring and possibly interventions regarding future cardiorespiratory and neurodevelopmental function.

Development and application of a sediment toxicity test using the benthic cladoceran Chydorus sphaericus.

This study reports on the development and application of a whole sediment toxicity test using a benthic cladoceran Chydorus sphaericus, as an alternative for the use of pelagic daphnids. A C. sphaericus laboratory culture was started and its performance under control conditions was optimised. The test was firstly validated by determining dose-response relationships for aqueous cadmium and copper and ammonia, showing a sensitivity of C. sphaericus (96 h LC(50) values of 594 microg Cd/L, 191 microg Cu/L and 46 mg ammonia/L at pH 8) similar to that of daphnids. Next, sediment was introduced into the test system and a series of contaminated sediments from polluted locations were tested. A significant negative correlation between survival and toxicant concentrations was observed. It is concluded that the test developed in the present study using the benthic cladoceran C. sphaericus is suitable for routine laboratory sediment toxicity testing.

Oral health among children with congenital heart defects in Western Norway.

AIM: This was to describe oral health in children with congenital heart defects (CHD), to evaluate association of different background variables with oral health, and to compare caries prevalence at dentine level with caries data in the general population. METHODS: In this cross-sectional study, 5-year-old children in Western Norway with a need for lifelong follow-up due to CHD were invited to participate (n = 100). Children born in 2005, 2006, and 2007 underwent a comprehensive oral health examination during the period 2010-2012. Caries prevalence at the dentine level was compared with data available for 5-year-old children from the general population of Western Norway (n = 18,974). RESULTS: The response rate was 67 %. Caries prevalence in children with CHD at d1-5mft was 37.3 % and at d3-5mft 25.4 %. Few children (n = 4) had experienced fillings, indicating an unmet need for operative treatment. Enamel lesions (d1-2s) exceeded dentine lesions (d3-5s) in the study group, 60 % versus 40 %, indicating a significant need of non-operative treatment. At dentine level, caries prevalence in children with CHD was significantly higher than in children in the general population (25.4 versus 18.3 %). Erosion was more prevalent than caries (50.7 versus 37.3 %). In total, 37.3 % of all children had d3-5mfs caries, erosion (grades 3 or 4), developmental defects of enamel (DDE) with post-eruptive breakdown of enamel and exposure into dentine, or combinations of the diagnoses. Investigated background factors did not significantly affect caries, erosion, or DDE. CONCLUSION: More than a third of the children with CHD were found to have an oral health status that may imply risk for systemic hazardous effects.

Sensitivity of characteristic riverine insects, the caddisfly Cyrnus trimaculatus and the mayfly Ephoron virgo, to copper and diazinon.

This study reports the effects of two model toxicants, copper and diazinon, on two characteristic riverine insect species, the caddisfly Cyrnus trimaculatus and the mayfly Ephoron virgo. It was demonstrated that these species are very sensitive to both compounds in comparison with aquatic insects traditionally used in ecotoxicity tests. For diazinon, the 96-h LC(50) value of Cyrnus trimaculatus (1.1 microg/l) is lower than for any other insect species known from the literature and for copper it was demonstrated that Ephoron virgo is among the most sensitive aquatic insect species. The observed low LC(50) values stress the importance of using these indigenous species in assessing the risk of environmental contaminants in large European rivers and in defining conditions for ecological recovery.

Molecular genetic analysis of long QT syndrome in Norway indicating a high prevalence of heterozygous mutation carriers.

Mutations in the KCNQ1, HERG, SCN5A, minK and MiRP1 genes cause long QT syndrome (LQTS), of which there are two forms: the Romano Ward syndrome and the Jervell and Lange-Nielsen syndrome. We have performed DNA sequencing of the LQTS-associated genes in 169 unrelated patients referred for genetic testing with respect to Romano Ward syndrome and in 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome. A total of 37 different mutations in the 5 genes, of which 20 were novel, were identified. Among patients with the most stringent clinical criteria of Romano Ward syndrome, a mutation was identified in 71%. Twelve of the 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome were provided with a molecular genetic diagnosis. Cascade genetic screening of 505 relatives of index patients with molecularly defined LQTS identified 251 mutation carriers. The observed penetrance was 41%. Although caution must be exerted, the prevalence of heterozygotes for mutations in the LQTS-associated genes in Norway could be in the range 1/100-1/300, based on the prevalence of patients with Jervell and Lange-Nielsen syndrome.

Relationship between morphological signs of cell injury in myocardial ischaemia.

Morphological signs of severe ischaemic injury are well known. However, we still lack knowledge about how indices of milder injuries are related on a cellular level. In a previous study we have reported on the sequence of alterations across the border zone in cat hearts subjected to 3 h of coronary occlusion. In the present study, which elaborates that study, we have examined the relationship between morphological variables in serial sections of 220 myocytes within the border zone. In cells with intact sarcolemma and no chromatin changes, the fractional volume of cytoplasm has a bimodal distribution indicating cells with and without oedema. Whereas cells with focal disruptions of the sarcolemma have a moderate oedema, usually localized submembranously, cells with extensive sarcolemmal fragmentation have an extensive oedema. A mild oedema is seen before other signs of severe cell injury, even though more extensive oedema is closely associated with sarcolemmal fragmentation. The fractional volume of mitochondria was smaller, whereas the fractional volume of lipid droplets was larger in cells with oedema than in cells without oedema.

Ultrastructural changes at the border of the ischaemic zone within one hour of coronary artery occlusion.

The ultrastructure was studied by electron microscopy in myocytes obtained from the periphery of the ischaemic zone 10, 20, 40, and 60 min after occlusion of the left anterior descending coronary artery (LAD) in open chest anaesthetized cats. The morphology of this zone was compared to that of the normally perfused myocardium in the same hearts. Samples were collected from the border of the ischaemic tissue as defined by in vivo injection of fluorescein and verified by regional blood flow measurements with radiolabelled microspheres. After 10 min of LAD-occlusion, we observed swelling of the mitochondria in the border zone. The mitochondrial swelling remained stable for the first hour after LAD-occlusion. There was no difference in the fractional volume of lipid droplets between the normal and border zones after 10 min of ischaemia. The fractional volume of lipid droplets, however, was significantly reduced in the normal zone after 20 min of coronary artery occlusion, whereas it remained unchanged in the border zone. Up to 60 min after LAD-occlusion the fractional volumes of cytoplasm in the border zone were not different from the corresponding values in the normal zone, indicating that there was no cytoplasmic oedema in the border zone. However, a reduced fractional volume of myofibrils in the border zone after 20 min of LAD-occlusion, may indicate a slight cell swelling, probably due to the mitochondrial swelling. In the border zone there was a slight increase in the number of cells with sarcolemmal injuries after 10 min of LAD-occlusion. Cells with chromatin clumping and margination were found after 20 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Problems related to infarct size measurements in the rat heart.

The feasibility of measuring the extent of hypoperfused myocardium and the infarct size was examined in rat hearts after occlusion of the left coronary artery. The extent of hypoperfused myocardium was examined by autoradiography and after perfusion with fluorescent microspheres. Both methods appeared unreliable in this model. Triphenyltetrazolium chloride (TTC) staining, however, provided a distinct demarcation line between viable myocardium, which was stained red, and the necrotic myocardium, consistent with the ultrastructural border between normal and severely damaged myocytes 5 h after coronary occlusion. TTC staining gives the best demarcation of ischemic tissues. In verapamil-treated rats, there was an apparent reduction in infarct size as compared with untreated rats; 20% reduction in infarct size 5 h after coronary occlusion and 12% reduction after 24 h. There was, however, a large postoperative mortality among the verapamil-treated rats. These problems, and the nonuniform infarct size in rats, may in part explain why infarct size limitation by verapamil has been reported from rat experiments, but not from clinical trials.

Morphological changes across the border zone of cat hearts subjected to regional ischaemia.

The left anterior descending coronary artery (LAD) was ligated for 3 h in six open chest cats. Six biopsies for electron microscopy were collected from the normal, the ischaemic and the border zones as defined by in vivo injection of fluorescein and as verified by blood flow measurements. Across the fluorescein demarcation line, we collected 3 mm long border zone biopsies, extending 1.5 mm in both the normal and the ischaemic direction. Starting from the normal end twenty subsequent areas (165 microns apart) were studied. By examining a total number of 5280 myocytes we observed an abrupt increase in the number of cells with sarcolemmal fragmentation. This point called border line is accompanied by an abrupt increase in the number of cells with chromatin clumping or margination, and of cells which are mainly necrotic with a massive cytoplasmic oedema. Morphometric analysis of 576 micrographs indicates a border zone on both sides of the border line. The border zone is characterized by a larger fractional volume of mitochondria (extending 1.5-2.0 mm in the normal direction) and by a larger lipid droplet accumulation (extending 1.2 mm or less in the normal direction) than seen in the ischaemic zone. These changes are in the normal part of the border zone accompanied with a moderate cytoplasmic oedema and a fragile sarcolemma with focal disruptions.

Associations between beta-tubulin and mitochondria in adult isolated heart myocytes as shown by immunofluorescence and immunoelectron microscopy.

We have investigated the associations between beta-tubulin and mitochondria in freshly isolated cardiac myocytes from the rat. Beta-tubulin was identified by using monoclonal antibodies for immunofluorescence and high resolution immunogold electron microscopy. In addition, conventional transmission and scanning electron microscopic studies were performed. After chemical stabilization in a formaldehyde solution, the myocytes were shock-frozen at -150 degrees C, cryosectioned at -70 degrees C and subsequently processed for immunohistochemical and immunocytochemical microscopy. A characteristic of the rod shaped myocytes is the presence of a dense network of microtubules in the cytoplasm displaying a pattern of strong anti-beta-tubulin reaction. The complexity of this network however varies considerably among the myocytes reflecting microtubule dynamic instability. Further, our findings demonstrate that the beta-tubulin label in rod cells is confined to the perinuclear and interfibrillar spaces and, therefore, is largely colocalized with the cytoplasmic organelles. In myocytes undergoing severe contracture the distribution of beta-tubulin is entirely restricted to the outer mitochondrial-containing domain. This implies that, in a cell model with marked segregation of the contractile filaments and organelles, mitochondria are codistributed with microtubules in the total absence of desmin intermediate filaments. Moreover, our immunogold preparations demonstrate anti-beta-tubulin labelling in the outer mitochondrial membrane as well as of fibres in close apposition to this membrane. These results indicate the presence of a specific beta-tubulin binding to the outer mitochondrial membrane that probably also involves microtubule based translocators and/or MAPs.

[Treatment of supraventricular tachycardia in children]. / Behandling av supraventrikulaer takykardi hos barn.

Although young infants may have severe symptoms from supraventricular tachycardia the majority responds to treatment. In 60-90% of the infants the arrhythmias disappear within 6-12 months, whereas in older children the supraventricular tachycardia tends to reoccur. Our recommended acute treatment in infants less than six months of age is to emmerse the face in cold water, but adenosine should be used for pharmacological termination of supraventricular tachycardia in all age groups. If this fails, direct current cardioversion should be applied without delay. Intravenous verapamil should not be used, however, in infants for termination of supraventricular tachycardia. Flecainide can be used for acute and prophylactic treatment.

Low frequency mosaicism of normal cells in a 16-year-old girl with trisomy 18.

A 16-year-old girl with mosaicism of trisomy 18 has been followed from birth in our department. She had stigmata characteristic for trisomy 18. Chromosome analysis of lymphocytes showed trisomy 18 both at birth and at age 15, whereas analysis of fibroblasts at age 16 showed trisomy 18 with low frequency mosaicism of normal cells (4%). In most case reports, karyotype analyses have been performed in lymphocytes only. The low frequency mosaicism of normal cells found in fibroblasts from the present patient may raise the question of mosaicism in other long-living patients previously reported to be non-mosaic trisomy 18. The main disorders in the present patient were limited to severe mental deficiency, structural cerebral malformations and skeletal deformities, including bilateral equinovarus deformities. At birth, she had a ventricular septal defect which closed spontaneously. Frequent respiratory infections subsided after age 2. At age 7 she developed a seizure disorder. Since then, her medical condition has been stable. Even though patients with trisomy 18 rarely survive early childhood, the possibility that they may reach their teens must be kept in mind when treatment is planned. In our case, the decision not to treat her equinovarus deformities means that she cannot stand, a major problem in her everyday life.

Cellular morphometric changes in cat hearts subjected to three hours of regional ischaemia.

The left anterior descending coronary artery (LAD) was occluded for three hours in seven anaesthetized open chest cats. Seven cats served as sham operated controls. Biopsies were collected from the mid-myocardium of the normal, border and ischaemic zones as defined by fluorescein staining and verified by blood flow measurements with radiolabelled microspheres. In the sham operated hearts the biopsies were taken from the mid-myocardium of the lateral wall of the left ventricle. Fractional volumes of mitochondria, myofibrils and remaining cytoplasm as well as data on the outer mitochondrial membrane were obtained by standard point counting techniques. In the LAD occluded hearts we observed a morphologically distinct lateral border zone characterized by a greater swelling of the mitochondria than in the ischaemic zone. However, in this group a more marked oedema of the cytoplasm and a greater percentage of heavily damaged cells were observed in the ischaemic than in the border zone. The ischaemic zone also had the largest water content. Furthermore, cytoplasmic oedema occurred in the normal zone of the LAD occluded cats when compared with the sham operated controls. This indicates that LAD occlusion also affects the normally perfused parts of the heart.