Search

Purpose Around 2000 heart transplants are performed in Europe annually. Primary Graft Dysfunction(PGD) rates in Europe are among the highest in the world. The increasing use of marginal donor organs has been suggested as a potential cause. Novel techniques using ex-vivo normothermic perfusion have garnered increasing interest but incur a significant cost. We present a series of patients who underwent heart transplantation at our unit using a novel implantation technique to reduce PGD that is cost-effective and reproducible Methods The donor heart is removed from cold storage and placed in an ice slush basin on arrival to our unit. An aortic cross clamp is applied distal to the donor ascending aorta. An antegrade infusion of 600mls of cold blood cardioplegia is followed by cold oxygenated blood (4-6°C) to achieve a mean aortic root pressure of 60-70 mmHg. This continuous antegrade perfusion is maintained throughout the left atrium and aortic anastomosis with a left ventricular vent in situ. A warm cardioplegia hotshot is infused into the aortic root prior to removal of the recipient aortic cross-clamp. The remaining anastomoses are carried out in the usual fashion sequentially. We compared our experience with this method with the national UK cohort (2015-2016) of patients (Control Group). We performed multivariable logistic regression comparing the two cohorts with PGD as the primary outcome measure. Confounders adjusted for include donor age, recipient age and donor-recipient gender mismatch. Results 139 (71.6 %) patients were male. 46(18.6%) of the patients had ischemic cardiomyopathy. The odds ratio of PGD in the control group was 2.99 (95% CI 1.02- 8.75) when compared to the Extended Cooling. Conclusion This novel approach is associated with significant reductions in PGD rates post-transplantation likely due to the shorter warm ischemic time. Larger studies are needed to show differences after further adjustment for known confounders of PGD. We believe this novel technique is safe, cost-effective and reproducible. [ABSTRACT FROM AUTHOR]

Objective: The COVID-19 pandemic posed new challenges for integrated health care worldwide. Our study aimed to describe newly implemented structures and procedures of psychosocial consultation and liaison (CL) services in Europe and beyond, and to highlight emerging needs for co-operation., Methods: Cross-sectional online survey from June to October 2021, using a self-developed 25-item questionnaire in four language versions (English, French, Italian, German). Dissemination was via national professional societies, working groups, and heads of CL services., Results: Of the participating 259 CL services from Europe, Iran, and parts of Canada, 222 reported COVID-19 related psychosocial care (COVID-psyCare) in their hospital. Among these, 86.5% indicated that specific COVID-psyCare co-operation structures had been established. 50.8% provided specific COVID-psyCare for patients, 38.2% for relatives, and 77.0% for staff. Over half of the time resources were invested for patients. About a quarter of the time was used for staff, and these interventions, typically associated with the liaison function of CL services, were reported as most useful. Concerning emerging needs, 58.1% of the CL services providing COVID-psyCare expressed wishes for mutual information exchange and support, and 64.0% suggested specific changes or improvements that they considered essential for the future., Conclusion: Over 80% of participating CL services established specific structures to provide COVID-psyCare for patients, their relatives, or staff. Mostly, resources were committed to patient care and specific interventions were largely implemented for staff support. Future development of COVID-psyCare warrants intensified intra- and inter-institutional exchange and co-operation., Competing Interests: Declaration of Competing Interest All other authors declare that they have no competing financial interests related to this study., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: Around 2000 heart transplants are performed in Europe annually. The rates of primary graft dysfunction in Europe are among the highest in the world. With increasing demand for organs and the limited supply of donors, novel techniques such as ex vivo normothermic perfusion have garnered incre-asing interest. We present a series of patients who underwent heart transplant at our unit in which we used a novel implantation technique to reduce primary graft dysfunction., Materials and Methods: We compared our experience with the novel method detailed in our article (Glasgow experience group) with a contemporary UK cohort (2015-2016) of patients (control group). We performed multivariable logistic regression to compare the Glasgow experience with the control group with primary graft dysfunction as the outcome measure. We adjusted for donor age, recipient diabetes mellitus, urgent listing status, bypass time, and total ischemic time., Results: Among 194 patients in both cohorts, 140 patients (72.1%) were men and 36 (18.6%) had ischemic cardiomyopathy. The odds ratio of primary graft dysfunction in the control group was 2.99 (95% CI, 1.02- 8.75) compared with the Glasgow experience group., Conclusions: Our novel approach was associated with significant reductions in primary graft dysfunction, with a trend toward improved 1-year survival. Larger studies are needed to show differences after further adjustment for known confounders of primary graft dysfunction. We believe this novel technique is safe, cost-effective, and reproducible.

Health technology assessment (HTA) of medical devices (MDs) increasingly rely on real-world evidence (RWE). The aim of this study was to evaluate the type and the quality of the evidence used to assess the (cost-)effectiveness of high risk MDs (Class III) by HTA agencies in Europe (four European HTA agencies and EUnetHTA), with particular focus on RWE. Data were extracted from HTA reports on the type of evidence demonstrating (cost-)effectiveness, and the quality of observational studies of comparative effectiveness using the Good Research for Comparative Effectiveness principles. 25 HTA reports were included that incorporated 28 observational studies of comparative effectiveness. Half of the studies (46%) took important confounding and/or effect modifying variables into account in the design and/or analyses. The most common way of including confounders and/or effect modifiers was through multivariable regression analysis. Other methods, such as propensity score matching, were rarely employed. Furthermore, meaningful analyses to test key assumptions were largely omitted. Resulting recommendations from HTA agencies on MDs is therefore (partially) based on evidence which is riddled with uncertainty. Considering the increasing importance of RWE it is important that the quality of observational studies of comparative effectiveness are systematically assessed when used in decision-making., (© 2022 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Background:  The European Leadership Forum (ELF) of the European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS) previously identified the need for harmonisation of breast reconstruction standards in Europe, in order to strengthen the role of plastic surgeons. This study aims to survey the status, current trends and potential regional differences in the practice of breast reconstruction in Europe, with emphasis on equity and access., Materials and Methods:  A largescale web-based questionnaire was sent to consultant plastic and reconstructive surgeons, who are experienced in breast reconstruction and with understanding of the national situation in their country. Suitable participants were identified via the Executive Committee (ExCo) of ESPRAS and national delegates of ESPRAS. The results were evaluated and related to evidence-based literature., Results:  A total of 33 participants from 29 European countries participated in this study. Overall, the incidence of breast reconstruction was reported to be relatively low across Europe, comparable to other large geographic regions, such as North America. Equity of provision and access to breast reconstruction was distributed evenly within Europe, with geographic regions potentially affecting the type of reconstruction offered. Standard practices with regard to radiotherapy differed between countries and a clear demand for European guidelines on breast reconstruction was reported., Conclusion:  This study identified distinct lack of consistency in international practice patterns across European countries and a strong demand for consistent European guidance. Large-scale and multi-centre European clinical trials are required to further elucidate the presented areas of interest and to define European standard operating procedures., Competing Interests: The authors declare that there is no conflict of interest., (Thieme. All rights reserved.)

Childhood obesity is a worldwide epidemic. Mediterranean diet (MD) is inversely associated with childhood obesity, but the interaction with other environmental factors, such screen time, might influence the health benefits of a high MD adherence in adolescents. The aim of the present study was to assess whether an association between MD and screen time exists in European adolescents. Moreover, we also explored whether sedentary time has a modulatory effect on the association between MD and adiposity. Adherence to the MD (24 h recalls), screen time (questionnaire), pubertal development, body mass index (BMI), fat mass index (FMI) and waist circumference (WC) were evaluated in 2053 adolescents (54.7% females), aged 12.5-17.5 years. In females, MD adherence was associated with lower BMI and FMI only when they were exposed to less than 338 min/day of screen time (81.8% of females); MD adherence was also associated with lower WC only when females were exposed to less than 143 min/day of screen time (31.5% of females). No significant MD-screen time interaction was observed in males. In conclusion, screen-time-based sedentary behaviours had a modulatory effect in the association between MD adherence and adiposity in European female adolescents.

Background: Subclinical mastitis (SCM) is an inflammatory condition of the mammary gland. We examined the effects of SCM on human milk (HM) composition, infant growth, and HM intake in a mother-infant cohort from seven European countries. Methods: HM samples were obtained from 305 mothers at 2, 17, 30, 60, 90, and 120 days postpartum. SCM status was assessed using HM Sodium (Na): Potassium (K) ratio >0.6. Levels of different macro- and micronutrients were analyzed in HM. Results: SCM prevalence in the first month of lactation was 35.4%. Mean gestational age at delivery was lower and birth by C-section higher in SCM mothers ( p ≤ 0.001). HM concentrations of lactose, DHA, linolenic acid, calcium, and phosphorous ( p < 0.05 for all) was lower, while total protein, alpha-lactalbumin, lactoferrin, albumin, arachidonic acid to DHA ratio, n -6 to n -3 ratio and minerals (iron, selenium, manganese, zinc, and copper) were higher ( p < 0.001 for all) in mothers with SCM. There were no differences in infant growth and HM intake between non-SCM and SCM groups. Conclusion: We document, for the first time, in a large European standardized and longitudinal study, a high prevalence of SCM in early lactation and demonstrate that SCM is associated with significant changes in the macro- and micronutrient composition of HM. Future studies exploring the relation of SCM with breastfeeding behaviors and developmental outcomes are warranted.

An accurate diagnosis of β-lactam (BL) allergy can reduce patient morbidity and mortality. Our aim was to investigate the availability of BL reagents, their use and test procedures in different parts of Europe, as well as any differences in the diagnostic workups for evaluating subjects with BL hypersensitivity. A survey was emailed to all members of the EAACI Drug Allergy Interest Group (DAIG) between February and April 2016, and the questionnaire was meant to study the management of suspected BL hypersensitivity. The questionnaire was emailed to 82 DAIG centres and answered by 57. Amoxicillin alone or combined to clavulanic acid were the most commonly involved BL except in the Danish centre, where penicillin V was the most frequently suspected BL. All centres performed an allergy workup in subjects with histories of hypersensitivity to BL: 53 centres (93%) followed DAIG guidelines, two national guidelines and two local guidelines. However, there were deviations from DAIG recommendations concerning allergy tests, especially drug provocation tests. A significant heterogeneity exists in current practice not only among countries, but also among centres within the same country. This suggests the need to re-evaluate, update and standardize protocols on the management of patients with suspected BL allergy., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Nutrigenetic tests are often considered to be less serious compared to other health-related genetic tests, although they share similar ethical concerns. Nutrigenetic tests are mainly available through direct-to-consumer genetic testing (DTC GT) and increasing in popularity., Objective: To analyze the contents of nutrigenetic DTC GT websites with respect to the adequacy of the information provided to support a well-informed decision of purchasing the tests., Methods: The websites of DTC GT companies selling nutrigenetic tests that could be ordered online without involving any healthcare professional, available in English, marketing tests in Europe, the USA, Australia, or Canada, and accessible from Finland were included in the study (n = 38). Quantitative and qualitative content analyses of the websites were carried out with the help of a codebook., Results: Of the 38 websites, 8 included a clearly identifiable and easy-to-find information section about genetics. The quality and contents of these sections were often insufficient and/or misleading. Fourteen websites had specific sections discussing the risks related to GT, and on 13 signed informed consent was requested for GT. Furthermore, only 2 of the companies offered any kind of pretest consultation and 13 offered mostly separately charged posttest consultation. The complex structure of the websites made it difficult to find all key information, with many important aspects buried in legal documents, which were challenging to comprehend even for a professional., Conclusion: The structure of the websites and the amount and quality of the content therein do not support a well-informed decision., (© 2019 S. Karger AG, Basel.)

Background: To improve our understanding of urea cycle disorders (UCDs) prospectively followed by two North American (NA) and European (EU) patient cohorts., Aims: Description of the NA and EU patient samples and investigation of the prospects of combined and comparative analyses for individuals with UCDs., Methods: Retrieval and comparison of the data from 1095 individuals (NA: 620, EU: 475) from two electronic databases., Results: The proportion of females with ornithine transcarbamylase deficiency (fOTC-D), particularly those being asymptomatic (asfOTC-D), was higher in the NA than in the EU sample. Exclusion of asfOTC-D resulted in similar distributions in both samples. The mean age at first symptoms was higher in NA than in EU patients with late onset (LO), but similar for those with early (≤ 28 days) onset (EO) of symptoms. Also, the mean age at diagnosis and diagnostic delay for EO and LO patients were similar in the NA and EU cohorts. In most patients (including fOTC-D), diagnosis was made after the onset of symptoms (59.9%) or by high-risk family screening (24.7%), and less often by newborn screening (8.9%) and prenatal testing (3.7%). Analysis of clinical phenotypes revealed that EO patients presented with more symptoms than LO individuals, but that numbers of symptoms correlated with plasma ammonium concentrations in EO patients only. Liver transplantation was reported for 90 NA and 25 EU patients., Conclusions: Combined analysis of databases drawn from distinct populations opens the possibility to increase sample sizes for natural history questions, while comparative analysis utilizing differences in approach to treatment can evaluate therapeutic options and enhance long-term outcome studies., (© 2018 SSIEM.)

Introduction: Thoracic endovascular aortic aneurysm repair (TEVAR) is an established treatment for thoracic aortic disease in both the acute and elective setting, with such a widespread use that almost 50% of all thoracic aortic surgery in Europe is performed by these means. Nonetheless, the feasibility of TEVAR is determined by several anatomic factors, and the suitability of the proximal and distal landing zones remain one of the main limitations to its use. The advent of custom-made thoracic stent grafts widened the endovascular options in some challenging anatomies., Methods: The authors present a case report of a descending thoracic aortic pseudo-aneurysm, with no suitable proximal landing zone, successfully treated by means of a custom- -made fenestrated thoracic stent graft., Results: Male patient, 57 years old, with multiple cardiovascular risk factors and past medical history of coronary hearth disease, pulmonary emphysema and high speed trauma 20 years before. The patient was referred after being diagnosed with an asymptomatic saccular pseudo-aneurysm of the descending thoracic aorta, with 50mm of largest diameter and located at the level of the aortic isthmus. Inadequate proximal sealing was evident, even if deliberate left subclavian and carotid coverage were performed. Due to the prohibitive open surgical risk, and taking into account the post-traumatic etiology of the lesion, an endovascular solution was planned. The patient was therefore sequentially treated by means of a left carotid- subclavian bypass followed by custom-made fenestrated TEVAR, with a single fenestration for both the left common carotid artery and brachiocephalic trunk, granting proper sealing in the distal ascending aorta (Ishimaru zone 0). Rapid pacing was used during the implantation, with heart frequency of 180 bpm and systolic pressures of 40mmHg, allowing for a more precise deployment with no windsock effect. The procedure was successful and uneventful, with no intra-operative endoleaks, birdbeaks or retrograde dissections. There are no reported complications at 6 months follow-up., Conclusion: Custom-made fenestrated thoracic stentgrafts are an accessible, reproducible and safe therapeutic option when dealing with hostile thoracic arch anatomies, and should be considered as a minimally-invasive effective solution in selected cases.

Background: The clinical presentation of patients with organic acidurias (OAD) and urea cycle disorders (UCD) is variable; symptoms are often non-specific., Aims/methods: To improve the knowledge about OAD and UCD the E-IMD consortium established a web-based patient registry., Results: We registered 795 patients with OAD (n = 452) and UCD (n = 343), with ornithine transcarbamylase (OTC) deficiency (n = 196), glutaric aciduria type 1 (GA1; n = 150) and methylmalonic aciduria (MMA; n = 149) being the most frequent diseases. Overall, 548 patients (69 %) were symptomatic. The majority of them (n = 463) presented with acute metabolic crisis during (n = 220) or after the newborn period (n = 243) frequently demonstrating impaired consciousness, vomiting and/or muscular hypotonia. Neonatal onset of symptoms was most frequent in argininosuccinic synthetase and lyase deficiency and carbamylphosphate 1 synthetase deficiency, unexpectedly low in male OTC deficiency, and least frequently in GA1 and female OTC deficiency. For patients with MMA, propionic aciduria (PA) and OTC deficiency (male and female), hyperammonemia was more severe in metabolic crises during than after the newborn period, whereas metabolic acidosis tended to be more severe in MMA and PA patients with late onset of symptoms. Symptomatic patients without metabolic crises (n = 94) often presented with a movement disorder, mental retardation, epilepsy and psychiatric disorders (the latter in UCD only)., Conclusions: The initial presentation varies widely in OAD and UCD patients. This is a challenge for rapid diagnosis and early start of treatment. Patients with a sepsis-like neonatal crisis and those with late-onset of symptoms are both at risk of delayed or missed diagnosis.

Background: The disease course and long-term outcome of patients with organic acidurias (OAD) and urea cycle disorders (UCD) are incompletely understood., Aims: To evaluate the complex clinical phenotype of OAD and UCD patients at different ages., Results: Acquired microcephaly and movement disorders were common in OAD and UCD highlighting that the brain is the major organ involved in these diseases. Cardiomyopathy [methylmalonic (MMA) and propionic aciduria (PA)], prolonged QTc interval (PA), optic nerve atrophy [MMA, isovaleric aciduria (IVA)], pancytopenia (PA), and macrocephaly [glutaric aciduria type 1 (GA1)] were exclusively found in OAD patients, whereas hepatic involvement was more frequent in UCD patients, in particular in argininosuccinate lyase (ASL) deficiency. Chronic renal failure was often found in MMA, with highest frequency in mut(0) patients. Unexpectedly, chronic renal failure was also observed in adolescent and adult patients with GA1 and ASL deficiency. It had a similar frequency in patients with or without a movement disorder suggesting different pathophysiology. Thirteen patients (classic OAD: 3, UCD: 10) died during the study interval, ten of them during the initial metabolic crisis in the newborn period. Male patients with late-onset ornithine transcarbamylase deficiency were presumably overrepresented in the study population., Conclusions: Neurologic impairment is common in OAD and UCD, whereas the involvement of other organs (heart, liver, kidneys, eyes) follows a disease-specific pattern. The identification of unexpected chronic renal failure in GA1 and ASL deficiency emphasizes the importance of a systematic follow-up in patients with rare diseases.

Background: Elevated serum phosphorus (P) levels have been linked to increased morbidity and mortality in dialysis patients with secondary hyperparathyroidism (SHPT) but may be difficult to control if parathyroid hormone (PTH) is persistently elevated. We conducted a post hoc analysis of data from an earlier interventional study (OPTIMA) to explore the relationship between PTH control and serum P., Methods: The OPTIMA study randomized dialysis patients with intact PTH (iPTH) 300-799 pg/mL to receive conventional care alone (vitamin D and/or phosphate binders [PB]; n=184) or a cinacalcet-based regimen (n=368). For patients randomized to conventional care, investigators were allowed flexibility in using a non-cinacalcet regimen (with no specific criteria for vitamin D analogue dosage) to attain KDOQI™ targets for iPTH, P, Ca and Ca x P. For those assigned to the cinacalcet-based regimen, dosages of cinacalcet, vitamin D sterols, and PB were optimized over the first 16 weeks of the study, using a predefined treatment algorithm. The present analysis examined achievement of serum P targets (≤ 4.5 and ≤ 5.5 mg/dL) in relation to achievement of iPTH ≤ 300 pg/mL during the efficacy assessment phase (EAP; weeks 17-23)., Results: Patients who achieved iPTH ≤ 300 pg/mL (or a reduction of ≥ 30% from baseline) were more likely to achieve serum P targets than those who did not, regardless of treatment group. Of those who did achieve iPTH ≤ 300 pg/mL, 43% achieved P ≤ 4.5 mg/dL and 70% achieved P ≤ 5.5 mg/dL, versus 21% and 46% of those who did not achieve iPTH ≤ 300 pg/mL. Doses of PB tended to be higher in patients not achieving serum P targets. Patients receiving cinacalcet were more likely to achieve iPTH ≤ 300 pg/mL than those receiving conventional care (73% vs 23% of patients). Logistic regression analysis identified lower baseline P, no PB use at baseline and cinacalcet treatment to be predictors of achieving P ≤ 4.5 mg/dL during EAP in patients above this threshold at baseline., Conclusions: This post hoc analysis found that control of serum P in dialysis patients was better when serum PTH levels were lowered effectively, regardless of treatment received., Trial Registration: Clinicaltrials.gov identifier NCT00110890.

Serotyping is a simple typing method that consists of an immunoenzymatic assay (enzyme-linked immunosorbent assay [ELISA]) using synthetic polymorphic peptides derived from Toxoplasma gondii antigens. We developed a new ELISA based on GRA6 C-terminal polymorphic peptides. Serum samples from 41 human infections due to 23 archetypal (type I, II, or III) and 18 nonarchetypal strains were selected in order to validate this approach. For 20 out of the 23 archetypal infections, there was a clear correlation between microsatellite genotype and GRA6 serotyping. All infections due to nonarchetypal strains were misclassified as archetypal strain infections. The GRA6 C-terminal peptides from these strains were analyzed to explain this misclassification. A second group of 455 patients with acute and chronic toxoplasmosis due to unknown genotypes from different European, African, and Latin American countries were included in this study, and the strain type predicted by this method. The results suggest that serotyping is a promising method for typing strains, although limitations exist for African and South American strains as a consequence of higher peptide polymorphism. Other peptides from different markers must be studied in order to discriminate archetypal from nonarchetypal strains.

The objectives of this study were to analyze the population structure and genetic variability of two communities, Costa da Lagoa (CLG) and São João do Rio Vermelho (SJRV), located on Santa Catarina Island in southern Brazil. The two populations descend from Azores Archipelago immigrants (Portuguese), with a minor contribution of sub-Saharan Africans and Amerindians. To estimate the relative contribution of the different ethnic groups to the current gene pool of the two communities, values of admixture were obtained using the weighted least-squares method based on allelic frequencies of the loci ABO, RHD-RHCE, GPA-GPB (MNSs), HBB, HP, TF, CP, AK, and ACP1. The origins of the studied populations can be quantified as follows: for CLG, sub-Saharan Africans (A) = 17.3%, Iberian Europeans (P) = 75.0%, and Southern Amerindians (I) = 7.7%; for SJRV, A = 48.8%, P = 44.5%, and I = 6.7%. Because haplotype frequencies of the GPA-GPB loci in SJRV were unusual, possibly as a consequence of random genetic drift, the values of admixture were recalculated after exclusion of GPA-GPB, as follows: A = 28.0%; P = 53.3%, and I = 18.7%. The total diversity (HT) was estimated as 42.29%, of which 99.6% can be attributed to the intrapopulational variability (HS). The interpopulational genetic variation (or standard distance, DST) corresponds to 0.19%, while the gene differentiation coefficient is 0.28%, indicative of low genetic difference. These results led to the conclusion that random genetic drift may have had an important effect on the Costa da Lagoa community, while presently gene flow might be the predominant evolutionary factor potentially capable of changing allele frequencies in SJRV.