Sex-specific metabolic profiling to explain the increased CVD risk in women with migraine: a narrative review.

BACKGROUND: Migraine is a disabling neurological disorder whose diagnosis is based on clinical criteria. A shortcoming of these criteria is that they do not fully capture the underlying neurobiological factors and sex-specific complications in migraine such as cardio- and cerebrovascular disease. Biomarker research can help to improve disease characterization and identify pathophysiological mechanism underlying these comorbidities. OBJECTIVE: In this narrative review we searched for sex-specific metabolomics research to identify markers that may explain the migraine-cardiovascular disease (CVD) relationship. DISCUSSION: Large-scale plasma metabolome analyses revealed alterations in migraine. Sex-specific findings showed a less CVD-protective HDL metabolism as well as the ApoA1 lipoprotein, especially for women with migraine. To explore other possible pathophysiological pathways, we expanded our review to include inflammatory markers, endothelial and vascular markers and sex hormones. Biological sex differences may affect the pathophysiology of migraine and its complications. CONCLUSIONS: There is no general large dyslipidemia profile in migraine patients, in line with findings that the increased risk of CVD in migraine patients seems not to be due to (large artery) atherosclerosis. Sex-specific associations are indicative towards a less CVD-protective lipoprotein profile in women with migraine. Future studies into the pathophysiology of CVD and migraine need to take sex specific factors into account. By establishing the overlapping pathophysiological mechanism of migraine and CVD, and unraveling the associated effects these diseases exert on each other, better preventative measures can be identified.

Decision-making in imminent extreme premature births: perceived shared decision-making, parental decisional conflict and decision regret.

OBJECTIVE: To describe levels of perceived shared decision making (SDM), decisional conflict (DC), and decision regret (DR) in prenatal counseling by pregnant women, partners, neonatologists, and obstetricians regarding decision-making around imminent extreme premature birth in which a decision about palliative comfort care versus early intensive care had to be made. STUDY DESIGN: Multicenter, cross-sectional study using surveys to determine perceived SDM at imminent extreme premature birth in parents and physicians, and to determine DC and DR in parents. RESULTS: In total, 73 participants from 22 prenatal counseling sessions were included (21 pregnant women, 20 partners, 14 obstetricians, 18 neonatologists). High perceived levels of SDM were found (median 82,2), and low levels of DC (median 23,4) and DR at one month (median 12, 5). CONCLUSIONS: Reported levels of self-perceived SDM in the setting of prenatal counseling in extreme prematurity were high, by both the parents and the physicians. Levels of DC and DR were low.

Avoiding Unnecessary Major Rectal Cancer Surgery by Implementing Structural Restaging and a Watch-and-Wait Strategy After Neoadjuvant Radiochemotherapy.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is found in 15-20% of patients with locally advanced rectal cancer. A watch-and-wait (W&W) strategy has been introduced as an alternative strategy to avoid surgery for selected patients with a clinical complete response at multidisciplinary response evaluation. The primary aim of this study was to evaluate the efficacy of the multidisciplinary response evaluation by comparing the proportion of patients with pCR since the introduction of the structural response evaluation with the period before response evaluation. METHODS: This retrospective cohort study enrolled patients with locally advanced rectal cancer who underwent nCRT between January 2009 and May 2018, categorizing them into cohort A (period 2009-2015) and cohort B (period 2015-2018). The patients in cohort B underwent structural multidisciplinary response evaluation with the option of the W&W strategy. Proportion of pCR (ypT0N0), time-to-event (pCR) analysis, and stoma-free survival were evaluated in both cohorts. RESULTS: Of the 259 patients in the study, 21 (18.4%) in cohort A and in 8 (8.7%) in cohort B had pCR (p = 0.043). Time-to-event analysis demonstrated a significant pCR decline in cohort B (p < 0.001). The stoma-free patient rate was 24% higher in cohort B (p < 0.001). CONCLUSION: Multidisciplinary clinical response evaluation after nCRT for locally advanced rectal cancer led to a significant decrease in unnecessary surgery for the patients with a complete response.

[Don't be guided purely by numbers: false increased TSH values due to analytical interference]. / Vaar niet alleen op een getal.

BACKGROUND: Physicians are often guided by laboratory values. When a clinical presentation does not match laboratory values, one must consider the possibility that these values may be falsely increased or decreased. A common cause is analytical interference. CASE DESCRIPTION: A 57-year-old male, presenting with fatigue and palpitations, had high TSH and normal FT4 values. Although there were no fitting clinical symptoms for these values, the patient was treated with levothyroxine assuming he had subclinical hypothyroidism. TSH levels remained high, however, whereas FT4 levels increased and the patient developed thyrotoxicosis. Eventually, it was discovered that the TSH was falsely elevated. CONCLUSION: The patient turned out to have macro TSH, where TSH forms conjunctions with IgG into larger molecules. These conjugates cause a rarely occurring interference during laboratory analysis, resulting in a falsely increased TSH value.

Perspective: Advancing the research agenda for improving understanding of cyanobacteria in a future of global change.

Harmful cyanobacterial blooms (=cyanoHABs) are an increasing feature of many waterbodies throughout the world. Many bloom-forming species produce toxins, making them of particular concern for drinking water supplies, recreation and fisheries in waterbodies along the freshwater to marine continuum. Global changes resulting from human impacts, such as climate change, over-enrichment and hydrological alterations of waterways, are major drivers of cyanoHAB proliferation and persistence. This review advocates that to better predict and manage cyanoHABs in a changing world, researchers need to leverage studies undertaken to date, but adopt a more complex and definitive suite of experiments, observations, and models which can effectively capture the temporal scales of processes driven by eutrophication and a changing climate. Better integration of laboratory culture and field experiments, as well as whole system and multiple-system studies are needed to improve confidence in models predicting impacts of climate change and anthropogenic over-enrichment and hydrological modifications. Recent studies examining adaptation of species and strains to long-term perturbations, e.g. temperature and carbon dioxide (CO2) levels, as well as incorporating multi-species and multi-stressor approaches emphasize the limitations of approaches focused on single stressors and individual species. There are also emerging species of concern, such as toxic benthic cyanobacteria, for which the effects of global change are less well understood, and require more detailed study. This review provides approaches and examples of studies tackling the challenging issue of understanding how global changes will affect cyanoHABs, and identifies critical information needs for effective prediction and management.

Effectiveness of endosponge therapy for the management of presacral abscesses following rectal surgery.

BACKGROUND: Anastomotic leak after rectal surgery is reported in 9% (range 3-28%) of patients. The aim of our study was to evaluate the effectiveness of endosponge therapy for anastomotic. Endpoints were the rate of restored continuity and the functional bowel outcome after anastomotic leakage. METHODS: This was a multicenter retrospective observational cohort study. All patients with symptomatic anastomotic leakage after rectal surgery who had endosponge therapy between January 2012 and August 2017 were included. Functional bowel outcome was measured using the low anterior resection syndrome (LARS) score system. RESULTS: Twenty patients were included. Eighteen patients had low anterior resection (90%) for rectal cancer. A diverting ileostomy was performed at primary surgical intervention in 14 patients (70%). Fourteen patients (70%) were treated with neoadjuvant (chemo-)radiotherapy. The median time between primary surgical intervention and first endosponge placement was 21 (5-537) days. The median number of endosponge changes was 9 (2-28). The success rate of the endosponge treatment was 88% and the restored gastrointestinal continuity rate was 73%. A chronic sinus occurred in three patients (15%). All patients developed LARS, of which 77% reported major LARS. CONCLUSIONS: Endosponge therapy is an effective treatment for the closure of presacral cavities with high success rate and leading to restored gastrointestinal continuity in 73%. However, despite endosponge therapy many patients develop major LARS.

Cochlear implant performance in children deafened by congenital cytomegalovirus-A systematic review.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is a major cause of sensorineural hearing loss in children. OBJECTIVE OF REVIEW: The objective of this systematic review was to compare performance in paediatric cochlear implant users with SNHL caused by cCMV compared to non-cCMV implantees. TYPE OF REVIEW: Systematic review SEARCH STRATEGY: PubMed, EMBASE and the Cochrane databases were searched from inception up to 15 May 2017 for children, cochlear implant, performance and their synonyms. EVALUATION METHODS: Titles, abstracts and full texts were screened for eligibility. Directness of evidence and risk of bias were assessed. From the included studies, study characteristics and outcome data (speech perception, speech production, receptive language and auditory performance of cCMV groups and non-cCMV groups) were extracted. RESULTS: A total of 5280 unique articles were screened of which 28 were eligible for critical appraisal. After critical appraisal, 12 studies remained for data extraction. Seven of 12 studies showed worse performance after cochlear implantation in cCMV children compared to non-cCMV children. Worse performance in cCMV children was attributed to cCMV-related comorbidities in six of these studies. Available data on asymptomatic cCMV children compared to non-cCMV children did not reveal an unfavourable effect on cochlear implant performance. CONCLUSIONS: The available evidence reveals that cCMV children often have worse cochlear implant performance compared to non-cCMV children, which can be attributed to cCMV related comorbidities. We urge physicians to take into account the cCMV related comorbidities in the counselling of paediatric CI users deafened by cCMV.

Safety of endoscopic mucosal resection (EMR) of large non-pedunculated colorectal adenomas in the elderly.

BACKGROUND: Endoscopic mucosal resection (EMR) has been proven to be safe and effective for the treatment of colorectal adenomas. However, data are limited on the safety of this technique for large polyps and in elderly patients. Aims of our study were to examine the bleeding and perforation rates in patients with large non-pedunculated adenomas (≥20mm) and to evaluate the influence of size (≥40mm) and age (≥75 years) on the complication rates. METHODS: In this multicenter retrospective study, patients who underwent EMR of non-pedunculated adenomas ≥20mm between January 2012 and March 2016 were included. The demographics of the patients, the use of antithrombotic drugs, size of the polyps, type of resection, pathology report, occurrence of post-polypectomy bleeding, and perforation- and recurrence rate were collected. RESULTS: In 343 patients, 412 adenomas were removed. Eighty patients (23.3%) were ≥75 years of age, 138 polyps (33.5%) were ≥40mm. Bleeding complications were observed in 28 cases (6.8%) and were found significantly more frequent in adenomas ≥40mm, independent of the use of antithrombotic therapy. Five perforations (1.2%) were described, not related to the size of the polyp. There was no significant difference in complication rates between patients <75 years and patients ≥75 years. Bleeding complications rates were significantly higher in patients receiving double antithrombotic therapy. CONCLUSION: EMR is safe in elderly patients. EMR of adenomas of ≥40mm was associated with more bleeding complications. Future studies should address how the bleeding rates can be reduced in these patients, especially in those who use double antithrombotic treatment.

Health related quality of life in Dutch infants, toddlers, and young children.

BACKGROUND: The purpose of this study is to provide Dutch normative data and to assess internal consistency and known-groups validity for the TNO AZL Preschool Children Quality of Life (TAPQOL) and the acute version of the generic Pediatric Quality of Life Inventory (PedsQL 4.0) in Dutch young children aged 0-7 years. METHODS: Participants were selected from a panel of a large Dutch market research agency. A sample of 794 parents (response rate 61%, 39% fathers) of children (53% boys) from the general Dutch population, completed an electronic version of the TAPQOL (N = 227 infants aged 0-1 years) or PedsQL 4.0 (N = 293 toddlers aged 2-4 years and N = 274 young children aged 5-7 years). RESULTS: Except for the 'stomach' scale (α = .39), the TAPQOL showed acceptable to excellent internal consistency (α = .60-.88). The PedsQL 4.0 showed acceptable to excellent reliability in children aged 2-4 years (α = .60-.88) and in children aged 5-7 years (α = .76-.90). Children with a chronic health condition had lower scores than healthy children on 3 out of 12 domains of the TAPQOL (p = .001-.013) and on 2 out of 6 domains of the PedsQL 4.0 for children aged 2-4 years (p = .016-.04). The PedsQL 4.0 differentiated on all domains (p < .05) between children aged 5-7 years with and without a chronic health condition. CONCLUSION: In Dutch children aged 0-7 years old, HRQoL can be relialy measured with the TAPQOL and the PedsQL 4.0. However, it remains unclear whether these HRQoL instruments can distinguish between healthy children and children with a chronic health condition under the age of 5.

A Three-Dimensional View on Soil Biogeochemistry: A Dataset for a Forested Headwater Catchment.

Current understanding of the variability in soil properties and their relationship to processes and spatial patterns in forested landscapes is limited due to the scarcity of datasets providing such information. Here we present a spatially highly resolved dataset () that provides detailed information on the three-dimensional variability of biogeochemical properties in the Wüstebach catchment (western Germany), a long-term environmental observation site of the TERENO (Terrestrial Environmental Observatories) project. High-resolution soil sampling was conducted, and physical and biogeochemical soil parameters were recorded per horizon. The dataset is helpful in the analysis of the spatial heterogeneity in biogeochemical properties within soil horizons and with depth through the soil profile. In addition, it shows links between hydrological and biogeochemical properties and processes within the system. Overall, the dataset provides a high-resolution view into (re)cycling, leaching, and storage of nutrients on the catchment scale in a forested headwater catchment.

Consequences of CT colonography in stenosing colorectal cancer.

BACKGROUND: In patients with stenosing colorectal cancer (CRC), visualization of the entire colon prior to surgery is recommended to exclude synchronous tumors. Therefore, most centers combine computed tomographic colonography (CTC) with staging CT. The aims of this study were to evaluate the yield and clinical implications of CTC. METHODS: In this multicenter retrospective study, patients with stenosing CRC that underwent CTC and subsequent surgery between April 2013 and November 2015 were included. Result of the CTC, its influence on the surgical treatment plan, and final histology report were evaluated. RESULTS: One hundred sixty-two patients with stenosing CRC were included. Nine (5.6 %) synchronous cancers proximal to the stenosing tumor were suspected with CTC. In four of nine patients, the CTC did not change the primary surgical plan because the tumors were located in the same surgical segment. In five of nine patients, CTC changed the surgical treatment plan. Three of these five patients underwent an extended resection and the presence of the tumors was confirmed. Two of these three synchronous CRCs were also visible on abdominal staging CT. In the other two patients, the result of CTC was false positive which led to an unnecessary extended resection in one patient. CONCLUSION: The yield of CTC was relatively low. In only three patients (1.9 %), CTC correctly changed the primary surgical plan, but in two of them, the tumor was also visible on abdominal staging CT. Moreover, in two patients, CTC was false positive. The clinical value of CTC in stenosing CRC appears to be limited.

Cost-effectiveness of a combined physical exercise and psychosocial training intervention for children with cancer: Results from the quality of life in motion study.

This study was performed to estimate the cost-effectiveness of a combined physical exercise and psychosocial intervention for children with cancer compared with usual care. Sixty-eight children, aged 8-18 years old, during or within the first year post-cancer treatment were randomised to the intervention (n = 30) and control group (n = 38). Health outcomes included fitness, muscle strength and quality adjusted life years; all administered at baseline, 4- and 12-month follow-up. Costs were gathered by 1 monthly cost questionnaires over 12 months, supplemented by medication data obtained from pharmacies. Results showed no significant differences in costs and effects between the intervention and control group at 12-month follow-up. On average, societal costs were €299 higher in the intervention group than in the control group, but this difference was not significant. Cost-effectiveness acceptability curves indicated that the intervention needs large societal investments to reach reasonable probabilities of cost-effectiveness for quality of life and lower body muscle strength. Based on the results of this study, the intervention is not cost-effective in comparison with usual care.

Farmed Atlantic salmon Salmo salar L. parr may reduce early survival of wild fish.

The study examined the density-mediated effects on growth, survival and dispersal of wild and farmed Atlantic salmon Salmo salar offspring in the period immediately following emergence, using a substitutive design. In small confined stream channels, wild parr coexisting with farmed parr had a significantly poorer survival, than wild parr alone. Density did not affect this relationship. In larger unconfined stream channels, wild parr coexisting with farmed parr entered a downstream trap in higher numbers than wild parr in allopatry. The results suggests that during the earliest life stages, farmed S. salar can outcompete wild S. salar, resulting in a reduced survival of wild S. salar.

TWENTE Study: The Real-World Endeavor Resolute Versus Xience V Drug-Eluting Stent Study in Twente: study design, rationale and objectives.

Background. New-generation drug-eluting stents (DES) may solve several problems encountered with first-generation DES, but there is a lack of prospective head-to-head comparisons between new-generation DES. In addition, the outcome of regulatory trials may not perfectly reflect the outcome in 'real world' patients.Objectives. To compare the efficacy and safety of two new-generation DES in a 'real world' patient population.Methods. A prospective, randomised, single-blinded clinical trial to evaluate clinical outcome after Endeavor Resolute vs. Xience V stent implantation. The primary endpoint is target vessel failure at one-year follow-up. In addition, the study comprises a two-year and an open-label five-year follow-up. (Neth Heart J 2010;18:360-4.).

Psychological outcome and quality of life in children born with congenital diaphragmatic hernia.

OBJECTIVE: To assess psychological and social functioning and health related quality of life and its early determinants in children born with congenital diaphragmatic hernia (CDH). DESIGN: Cross-sectional follow-up study. SETTING: Outpatient clinic of a tertiary care hospital. PARTICIPANTS: 33 CDH survivors aged 6-16 years. MAIN EXPOSURE: Patients who developed CDH associated respiratory distress within 24 h after birth. MAIN OUTCOME MEASURE: Psychological and social functioning assessed with the Wechsler Intelligence Scale for Children (WISC-R), Bourdon-Vos test, Beery Developmental Test of Visual Motor Integration, Child Behavior Checklist (CBCL) and Teacher Report Form (TRF), and health related quality of life assessed with the Child Health Questionnaire (CHQ) and Health Utilities Index (HUI). RESULTS: Normal mean (SD) total IQ (100.0 (13.2)) and normal visual-motor integration, but significantly lower results for sustained attention (Bourdon-Vos test, 38.8 (11.2) points) were found. Learning difficulties were reported by 30% of parents. Eight children had scores in the clinical range on the CBCL and/or TRF, indicating clinically significant behavioural problems. Except for the CHQ scale General Health, health status was not different from the reference population. No significant correlations between test results and severity of CDH were found, except for an association of general health and physical functioning with length of hospital stay. CONCLUSION: CDH patients are at risk for subtle cognitive and behavioural problems, probably not related to CDH severity. Perception of general health is reduced compared to the reference population, indicating that CDH survivors and their parents believe their health is poor and likely to get worse.

Coping strategies of retinoblastoma survivors in relation to behavioural problems.

OBJECTIVE: To assess coping strategies of long-term retinoblastoma (RB) survivors and explore determinants of behavioural functioning, including medical, socio-demographic and coping variables. METHODS: This population-based cross-sectional study included 117 RB survivors (12-35 years), registered in the Dutch national RB register. Survivors were asked to fill in coping, social support and behavioural questionnaires, and situational characteristics were obtained from medical archives and from an interview. Prevalence rates of coping strategies were computed based on self-reports. One-sample t-tests were applied to analyse differences in the use of coping strategies compared with healthy reference samples. Multiple regression analyses were performed to identify various determinants for behavioural problems within the RB sample. RESULTS: RB survivors differed from their healthy reference group in one coping style, i.e. they showed significantly less emotion-oriented coping behaviour. Adolescents who came from a single-parent family and/or experienced lower social support and used more emotion-oriented coping reported more total problem behaviour. More internalizing problems were reported for adolescents who experienced less social support and less acceptance of the disease. For adults, more life events, emotion-oriented coping and lower social support explained more total problem behaviour, especially internalizing problems. CONCLUSION: RB survivors showed less emotion-oriented coping behaviour compared with the reference group. Behavioural problems are best determined by emotion-oriented coping, social support, life events other than RB and acceptance of the disease, and not by medical variables. Therefore, these variables should be taken into consideration during interventions for this group.

The long-term follow-up of patients with a congenital diaphragmatic hernia: a broad spectrum of morbidity.

Congenital diaphragmatic hernia (CDH) is a life-threatening anomaly with a mortality rate of approximately 40-50%, depending on case selection. It has been suggested that new therapeutic modalities such as nitric oxide (NO), high frequency oxygenation (HFO) and extracorporal membrane oxygenation (ECMO) might decrease mortality associated with pulmonary hypertension and the sequelae of artificial ventilation. When these new therapies indeed prove to be beneficial, a larger number of children with severe forms of CDH might survive, resulting in an increase of CDH-associated complications and/or consequences. In follow-up studies of infants born with CDH, many complications including pulmonary damage, cardiovascular disease, gastro-intestinal disease, failure to thrive, neurocognitive defects and musculoskeletal abnormalities have been described. Long-term pulmonary morbidity in CDH consists of obstructive and restrictive lung function impairments due to altered lung structure and prolonged ventilatory support. CDH has also been associated with persistent pulmonary vascular abnormalities, resulting in pulmonary hypertension in the neonatal period. Long-term consequences of pulmonary hypertension are unknown. Gastro-esophageal reflux disease (GERD) is also an important contributor to overall morbidity, although the underlying mechanism has not been fully understood yet. In adult CDH survivors incidence of esophagitis is high and even Barrett's esophagus may ensue. Yet, in many CDH patients a clinical history compatible with GERD seems to be lacking, which may result in missing patients with pathologic reflux disease. Prolonged unrecognized GERD may eventually result in failure to thrive. This has been found in many young CDH patients, which may also be caused by insufficient intake due to oral aversion and increased caloric requirements due to pulmonary morbidity. Neurological outcome is determined by an increased risk of perinatal and neonatal hypoxemia in the first days of life of CDH patients. In patients treated with ECMO, the incidence of neurological deficits is even higher, probably reflecting more severe hypoxemia and the risk of ECMO associated complications. Many studies have addressed the substantial impact of the health problems described above, on the overall well-being of CDH patients, but most of them concentrate on the first years after repair and only a few studies focus on the health-related quality of life in CDH patients. Considering the scattered data indicating substantial morbidity in long-term survivors of CDH, follow-up studies that systematically assess long-term sequelae are mandatory. Based on such studies a more focused approach for routine follow-up programs may be established.

Behavioural functioning of retinoblastoma survivors.

OBJECTIVE: To assess behavioural problems in retinoblastoma (RB) survivors. METHODS: This population-based cross-sectional study included 148 RB survivors (8-35 years), registered in the Dutch national RB register. Survivors and parents were asked to fill in behavioural questionnaires. Prevalence rates were computed, based on both self-reports and proxy reports. One-sample T-tests were applied to analyse differences compared with healthy reference samples. Multiple regression analyses were performed to identify predictors for behavioural problems within the RB sample. RESULTS: Between-group differences varied across informants and across age groups. Parents reported significantly elevated total problem behaviour in 30% of their offspring (aged 8-17 years); this against 9% in adolescents (12-17 years) and 12% in adults (18-35 years) based on self-report. Parental reports showed significantly elevated rates of (1) internalising problems in boys and (2) somatic complaints in both girls and boys. Self-reports indicate significantly lowered levels of (1) externalising problems in adolescent and adult women and (2) thought problems in female adolescents and in adult men. Especially survivors who suffered hereditary RB, who had undergone more intensive treatment, and who came from a single-parent family were identified to be at most behavioural risk. CONCLUSION: Perception of severity and the nature of behavioural problems seem to differ between beholder, and to vary between age groups, if not between life stages. Health professionals should be aware that especially those who are confronted with hereditary RB and who subsequently undergo intensive treatment, and who grow up in broken families, run the risk of developing behavioural difficulties.