Outcome of pregnancy in women after pulmonary autograft valve replacement for congenital aortic valve disease

BACKGROUND AND AIM OF THE STUDY: The pulmonary autograft has been recommended as the valve of choice for aortic valve replacement (AVR) in young women contemplating pregnancy. However, current information on maternal and perinatal outcome of pregnancy in women with pulmonary autograft valve replacement is limited. METHODS: Using a nationwide Dutch registry (CONCOR) and a local Belgian tertiary care center database, 17 women (age range: 18 to 45 years) with pulmonary autograft valve replacement were enrolled into the study. Twelve pregnancies were observed among five different women, including one miscarriage and one elective abortion. RESULTS: Clinically significant (non-)cardiac complications were documented in two of 10 completed pregnancies. Complications included: (i) placental abruption necessitating Cesarean delivery at 29 weeks' gestation, further complicated by postpartum hemorrhage; and (ii) preterm premature rupture of the membranes resulting in premature delivery at 29 weeks' gestation with postpartum demise of the immature born child. Two women reported primary female infertility, but both became pregnant after hormonal substitution therapy. Four women reported irregularities of their natural menstrual cycle (menorrhagia, dysmenorrhea, polymenorrhea, oligomenorrhea, or amenorrhea). CONCLUSION: Successful pregnancy in women with pulmonary autograft valve replacement is possible, although serious and clinically significant events occurred during gestation. Infertility and menstrual cycle disorders appear to be more prevalent.     

The role of the atria in congenital heart disease

The atria play an important role in adult congenital heart disease. Atrial function is often altered due to longstanding pressure or volume overload. Cardiac surgery inflicts lasting damage to the atria, which leads to loss of atrial compliance. Both the history of atrial overload and the atrial scarring form substrates for atrial tachycardias. There has been a growing interest in the interatrial septum in the past few years. There is evidence for a role of the persisting foramen ovale and atrial septal aneurysm as a causative or permissive factor in cerebral stroke. Catheter closure of the PFO may be an attractive option, especially for younger patients.     

Differential distribution of NK cells in decidua basalis compared with decidua parietalis after uncomplicated human term pregnancy

As pregnancy progresses, a characteristic decline in the percentage of CD56bright CD16- uterine natural killer (NK) cells occurs. Studies of term decidua, however, have focused only on leukocytes derived from decidua basalis, the site of implantation. The decidua parietalis, lining the remainder of the uterine cavity is another important region of the maternal-fetal interface that forms contact with fetal tissue at the end of the first trimester. The aim of this study was to evaluate possible differences in expression of CD16 and CD56 on leukocytes from normal term decidua basalis and decidua parietalis. Decidua basalis and parietalis samples were obtained from 30 placentas collected after elective cesarean section. Percentages of leukocyte subpopulations and NK cell subsets within the CD45+ cell fraction were determined by flow cytometry. In six decidual samples, concurrent immunohistochemical staining was performed. Higher percentages of CD56dim CD16+ NK cells and CD56- CD16+ cells were found in decidua basalis in comparison to decidua parietalis. In contrast, the percentage of CD56bright CD16- uterine NK cells was significantly higher in decidua parietalis. Immunohistochemical quantification supported flow cytometric results. We conclude that significant differences exist with respect to the distribution of NK cells in term decidua basalis and parietalis. Future functional studies may improve our understanding of their role at the maternal-fetal interface.     

Bacterial Toxins from Staphylococcus aureus and Bordetella bronchiseptica Predispose the Horse’s Respiratory Tract to Equine Herpesvirus Type 1 Infection

Respiratory disease in horses is caused by a multifactorial complex of infectious agents and environmental factors. An important pathogen in horses is equine herpesvirus type 1 (EHV-1). During co-evolution with this ancient alphaherpesvirus, the horse’s respiratory tract has developed multiple antiviral barriers. However, these barriers can become compromised by environmental threats. Pollens and mycotoxins enhance mucosal susceptibility to EHV-1 by interrupting cell junctions, allowing the virus to reach its basolateral receptor. Whether bacterial toxins also play a role in this impairment has not been studied yet. Here, we evaluated the role of α-hemolysin (Hla) and adenylate cyclase (ACT), toxins derived from the facultative pathogenic bacterium Staphylococcus aureus (S. aureus) and the primary pathogen Bordetella bronchiseptica (B. bronchiseptica), respectively. Equine respiratory mucosal explants were cultured at an air–liquid interface and pretreated with these toxins, prior to EHV-1 inoculation. Morphological analysis of hematoxylin–eosin (HE)-stained sections of the explants revealed a decreased epithelial thickness upon treatment with both toxins. Additionally, the Hla toxin induced detachment of epithelial cells and a partial loss of cilia. These morphological changes were correlated with increased EHV-1 replication in the epithelium, as assessed by immunofluorescent stainings and confocal microscopy. In view of these results, we argue that the ACT and Hla toxins increase the susceptibility of the epithelium to EHV-1 by disrupting the epithelial barrier function. In conclusion, this study is the first to report that bacterial exotoxins increase the horse’s sensitivity to EHV-1 infection. Therefore, we propose that horses suffering from infection by S. aureus or B. bronchiseptica may be more susceptible to EHV-1 infection.     

Continuity of care for patients with de novo metastatic cancer during the COVID-19 pandemic: A population-based observational study

During the COVID-19 pandemic recommendations were made to adapt cancer care. This population-based study aimed to investigate possible differences between the treatment of patients with metastatic cancer before and during the pandemic by comparing the initial treatments in five COVID-19 periods (weeks 1–12 2020: pre-COVID-19, weeks 12–20 2020: 1st peak, weeks 21–41 2020: recovery, weeks 42–53 2020: 2nd peak, weeks 1–20 2021: prolonged 2nd peak) with reference data from 2017 to 2019. The proportion of patients receiving different treatment modalities (chemotherapy, hormonal therapy, immunotherapy or targeted therapy, radiotherapy primary tumor, resection primary tumor, resection metastases) within 6 weeks of diagnosis and the time between diagnosis and first treatment were compared by period. In total, 74,208 patients were included. Overall, patients were more likely to receive treatments in the COVID-19 periods than in previous years. This mainly holds for hormone therapy, immunotherapy or targeted therapy and resection of metastases. Lower odds were observed for resection of the primary tumor during the recovery period (OR 0.87; 95% CI 0.77–0.99) and for radiotherapy on the primary tumor during the prolonged 2nd peak (OR 0.84; 95% CI 0.72–0.98). The time from diagnosis to the start of first treatment was shorter, mainly during the 1st peak (average 5 days, p < .001). These findings show that during the first 1.5 years of the COVID-19 pandemic, there were only minor changes in the initial treatment of metastatic cancer. Remarkably, time from diagnosis to first treatment was shorter. Overall, the results suggest continuity of care for patients with metastatic cancer during the pandemic.     

Cultural competence: a conceptual framework for teaching and learning

Objectives  The need to address cultural and ethnic diversity issues in medical education as a means to improve the quality of care for all has been widely emphasised. Cultural competence has been suggested as an instrument with which to deal with diversity issues. However, the implementation of culturally competent curricula appears to be difficult. We believe the development of curricula would profit from a framework that provides a practical translation of abstract educational objectives and that is related to competencies underlying the medical curriculum in general. This paper proposes such a framework.
Methods  The framework illustrates the following cultural competencies: knowledge of epidemiology and the differential effects of treatment in various ethnic groups; awareness of how culture shapes individual behaviour and thinking; awareness of the social context in which specific ethnic groups live; awareness of one's own prejudices and tendency to stereotype; ability to transfer information in a way the patient can understand and to use external help (e.g. interpreters) when needed, and ability to adapt to new situations flexibly and creatively.
Discussion  The framework indicates important aspects in taking care of an ethnically diverse patient population. It shows that there are more dimensions to delivering high-quality care than merely the cultural. Most cultural competencies emphasise a specific aspect of a generic competency that is of extra importance when dealing with patients from different ethnic groups. We hope our framework contributes to the further development of cultural competency in medical curricula.     

Long-term outcome and quality of life in adult patients after the Fontan operation

The first successful Fontan operation was performed in 1971, and this first cohort of Fontan patients is reaching adulthood with unclear outcome of this palliative procedure. We studied the mortality, morbidity, and quality of life in our adult Fontan patients. We examined all patients (n = 36) who underwent a Fontan procedure and were being seen in an adult outpatient clinic by using electrocardiography, exercise testing, and echocardiography. Quality of life was assessed by the Short Form 36 questionnaire. The mean follow-up period was 15 years (range 0 to 23). Of the initial 36 patients, 10 died (28%) at a mean of 10 years (range 0 to 21) after the Fontan operation and 1 patient underwent cardiac transplantation. Reoperations were performed in 21 patients (58%), and the most common reason was revision of the Fontan connection. Sustained supraventricular tachycardia was observed in 20 patients (56%) with an increased incidence of arrhythmias with longer follow-up. Thromboembolic events were detected in 9 patients (25%), 5 of whom had adequate anticoagulant levels at the time of event. The thromboembolic event was fatal for 3 patients. A total of 195 hospital admissions (mean 3.8 +/- 2.7, range 1 to 13) was recorded. Quality-of-life assessment showed physical functioning, mental health, and general health perception to be significantly lower for Fontan patients than for the normal Dutch population. Thus, we found high mortality and very high morbidity in adult patients after the Fontan operation. In particular, reoperations, arrhythmias, and thromboembolic events compromised quality of life.     

Prolongation of skin graft survival by modulation of the alloimmune response with alternatively activated dendritic cells

BACKGROUND: Activation of immature dendritic cells (DC) in the presence of the glucocorticoid hormone dexamethasone (DEX) results in alternatively matured DC that present antigen in the absence of a proper co-stimulatory context. This maturation process is irreversible, making these cells an attractive potential tool for the induction of antigen-specific T-cell tolerance in vivo. The authors explored the possibility of using these DC for the induction of transplantation tolerance in a fully allogeneic setting in mice. METHODS: Immature dendritic cells (D1, an immature splenic DC line derived from B6 mice) were pretreated with DEX for 24 hr, after which lipopolysaccharide or nothing was added to the culture for another 48 hr. These cells were analyzed for their in vitro and in vivo stimulating or tolerizing capacities. RESULTS: In line with their phenotype, including decreased interleukin (IL)-12 production, in vitro co-culture of alternatively matured D1 (B6 origin; H-2b) with completely allogeneic T cells of BALB/c origin led to a significant decrease in the alloreactive T-cell response. A single injection of 1 x 10(6) alternatively matured H-2b DC into BALB/c mice induced a different alloimmune response compared with mature DC. The responding T cells showed a lower proliferation rate and a lower interferon-gamma production, whereas a significantly higher proportion of the cells produced IL-10 as measured ex vivo by enzyme-linked immunospot assay. Furthermore, injection with alternatively matured DC, followed by transplantation of fully mismatched skin grafts (C57BL/6), led to a significantly prolonged survival compared with that of mature DC-pretreated mice or untreated mice. The immunomodulatory effect was antigen specific, as third-party reactive alloresponses were not affected. CONCLUSIONS: The authors' data constitute the first direct demonstration that DC alternatively matured in the presence of glucocorticoid hormones can be exploited for the specific suppression of the alloreactive Th1 response, resulting in a delayed skin graft rejection in a complete major histocompatibility complex-incompatible strain combination.     

Comparison of phototherapy (UV-B) and photochemotherapy (PUVA) for clearing and maintenance therapy of psoriasis

One hundred eighty-three patients with psoriasis were treated with UV-B irradiation or oral methoxsalen plus longwave UV light (PUVA). Patients treated with PUVA, in the initial and maintenance period, achieved in general a higher therapeutic score (95% to 100% clearance) than those receiving UV-B therapy. However, taking 80% to 100% improvement as criterion, no difference was found between initial UV-B and PUVA therapy, if less than 50% of the skin surface was affected by psoriasis. If more than 50% of the skin was involved, PUVA was better than UV-B therapy. The maintenance treatment frequency for the UV-B-treated patients for more than a year seemed to be higher than for PUVA-treated patients. A positive correlation was found between response to sunbathing (questionnaire survey) and the response to UV-B phototherapy. An extra UV-B treatment to the leg lesions appeared useless.