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Survival of patients with acute pulmonary embolism treated with venoarterial extracorporeal membrane oxygenation
No full textBackground: To examine whether venoarterial extracorporeal membrane oxygenation (VA-ECMO) improves survival of patients with acute pulmonary embolism (PE). Methods: Following the PRISMA guidelines, a systematic search was conducted up to August 2019 of the databases: PubMed/MEDLINE, EMBASE and Cochrane. All studies reporting the survival of adult patients with acute PE treated with VA-ECMO and including four patients or more were included. Exclusion criteria were: correspondences, reviews and studies in absence of a full text, written in other languages than English or Dutch, or dating before 1980. Short-term (hospital or 30-day) survival data were pooled and presented with relative risks (RR) and 95% confidence intervals (95% CI). Also, the following pre-defined factors were evaluated for their association with survival in VA-ECMO treated patients: age > 60 years, male sex, pre-ECMO cardiac arrest, surgical embolectomy, catheter directed therapy, systemic thrombolysis, and VA-ECMO as single therapy. Results: A total of 29 observational studies were included (N = 1947 patients: VA-ECMO N = 1138 and control N = 809). There was no difference in short-term survival between VA-ECMO treated patients and control patients (RR 0.91, 95% CI 0.71–1.16). In acute PE patients undergoing VA-ECMO, age > 60 years was associated with lower survival (RR 0.72, 95% CI 0.52–0.99), surgical embolectomy was associated with higher survival (RR 1.96, 95% CI 1.39–2.76) and pre-ECMO cardiac arrest showed a trend toward lower survival (RR 0.88, 95% CI 0.77–1.01). The other evaluated factors were not associated with a difference in survival. Conclusions: At present, there is insufficient evidence that VA-ECMO treatment improves short-term survival of acute PE patients. Low quality evidence suggest that VA-ECMO patients aged ≤60 years or who received SE have higher survival rates. Considering the limited evidence derived from the present data, this study emphasizes the need for prospective studies. Protocol registration: PROSPERO CRD42019120370.</p
Pain patterns in chronic pancreatitis
No full textObjective Pain in chronic pancreatitis is subdivided in a continuous or intermittent pattern, each thought to represent a different entity, requiring specific treatment. Because evidence is missing, we studied pain patterns in a prospective longitudinal nationwide study. Design 1131 patients with chronic pancreatitis (fulfilling M-ANNHEIM criteria) were included between 2011 and 2018 in 30 Dutch hospitals. Patients with continuous or intermittent pain were compared for demographics, pain characteristics, quality of life (Short-Form 36), imaging findings, disease duration and treatment. Alternation of pain pattern and associated variables were longitudinally assessed using a multivariable multinomial logistic regression model. Results At inclusion, 589 patients (52%) had continuous pain, 231 patients (20%) had intermittent pain and 311 patients (28%) had no pain. Patients with continuous pain had more severe pain, used more opioids and neuropathic pain medication, and had a lower quality of life. There were no differences between pain patterns for morphological findings on imaging, disease duration and treatment. During a median follow-up of 47 months, 552 of 905 patients (61%) alternated at least once between pain patterns. All alternations were associated with the Visual Analogue Scale pain intensity score and surgery was only associated with the change from pain to no pain. Conclusion Continuous and intermittent pain patterns in chronic pancreatitis do not seem to be the result of distinctly different pathophysiological entities. The subjectively reported character of pain is not related to imaging findings or disease duration. Pain patterns often change over time and are merely a feature of how severity of pain is experienced. </p
Port‐city transition
No full textThis article explores old and emerging socio‐spatial imaginaries and uses of Rotterdam’s Makers District. The district comprises two urban harbors—Merwe Vierhavens and Rotterdamsche Droogdok Maatschappij—historically in use as bustling trade, storage, and ship yarding nodes of the city’s port activities. At the turn of the millennium, technological advancements made it possible to move many port‐related activities out of the area and farther out of the city, gradually hollowing out these harbors’ port‐related economic foundations and opening opportunities for new uses and imaginaries. This article traces the transition by detailing how the boundary between the city and the port has become more porous in this district. It does so by offering original empirical evidence on the flows of users in and out of the area in recent years, based on location quotients, while also applying a content analysis of the profiles of companies and institutions currently inhabiting and working in these transformed port‐city spaces. On the one hand, the results show how the ongoing port‐city transition in Rotterdam’s Makers District combines carefully curated interventions and infrastructure plans seeking to progressively adapt the area to new purposes, while maintaining some of its former functions. On the other hand, they highlight the pioneering role of more bottom‐up initiatives and innovative urban concepts, springing from the creative industries and maker movement. The article offers insights into the emerging uses and imaginaries attached to the district, while also showing the resilience and adaptation of port legacies.</p
No improvement in survival of older women with cervical cancer—A nationwide study
No full textAim: This study aims to report trends in primary treatment and survival in cervical cancer (CC) to identify opportunities to improve clinical practice and disease outcome. Methods: Patients diagnosed with CC between 1989 and 2018 were identified from the Netherlands Cancer Registry (N = 21,644). Trends in primary treatment and 5-year relative survival were analysed with the Cochran-Armitage trend test and multivariable Poisson regression, respectively. Results: In early CC, surgery remains the preferred treatment for ages 15–74. Overall, it was applied more often in younger than in older patients (92% in 15–44; 64% in 65–74). For 75+, surgery use was stable over time (38%–41%, p=0.368), while administration of radiotherapy decreased (57%–29%, p < 0.001). In locally advanced CC, chemoradiation use increased over time (5%–65%, p < 0.001). It was applied least often for 75+, in which radiotherapy remains most common (54% in 2014–2018). In metastatic CC, chemotherapy use increased over time (11%–28%, p < 0.001), but varied across age groups (6%–40% in 2014–2018). In patients treated with primary chemoradiation, regardless of stage, brachytherapy use increased over time (p ≤ 0.001). Full cohort 5-year survival increased from 68% to 74% (relative excess risk 0.55; 95% confidence interval [0.50–0.62]). Increases were most significant in locally advanced CC (38%–60%; 0.55 [0.47–0.65]). Survival remained stable in 75+ (38%–34%; 0.82 [0.66–1.02]). Conclusion: Relative survival for cervical cancer increased over the last three decades. The proportion of older patients receiving preferred treatment lags behind. Consequently, survival did not improve in the oldest patients.</p
The unveiled reality of human papillomavirus as risk factor for oral cavity squamous cell carcinoma
No full textThe prognostic impact of human papillomavirus (HPV) in oropharyngeal cancer is generally acknowledged, and HPV-status is assessed routinely in clinical practice. Paradoxically, while the oral cavity seems the predilection site for productive HPV-infections, figures on HPV-attribution in oral cavity squamous cell carcinoma (OCSCC) differ widely, and prognostic impact is uncertain. Major obstacles are the lack of reproducible assays to detect HPV in nonoropharyngeal cancers, the relatively small cohorts studied and consequently the shortfall of convincing data. In our study, we used a validated, nucleic acid-based workflow to assess HPV-prevalence in a consecutive cohort of 1016 OCSCCs, and investigated its prognostic impact. In parallel, we analyzed p16-immunohistochemistry (p16-IHC) as surrogate marker for transforming HPV-infection and independent prognosticator. All OCSCC-patients diagnosed between 2008 and 2014 at two Dutch university medical centers were included (N = 1069). Formalin-fixed, paraffin-embedded (FFPE)-samples of 1016 OCSCCs could be retrieved. Punch biopsies were taken from the tumor area in the FFPE-blocks and tested for HPV. P16-IHC was performed on 580 OCSCCs, including all HPV-positive tumors. From 940 samples (92.5%), nucleic acids were of sufficient quality for HPV-testing. In total, 21 (2.2%) OCSCCs were HPV DNA-positive. All HPV DNA-positive tumors were E6 mRNA-positive and considered as true HPV-positive. There was no difference in survival between HPV-positive and HPV-negative OCSCCs. In total, 46 of 580 (7.9%) OCSCCs were p16-immunopositive, including all HPV-positive tumors. Survival was comparable in p16-positive and p16-negative OCSCCs. To conclude, HPV-prevalence is very low in OCSCC and neither HPV-status nor p16-status affects outcome. Based on these data, determining HPV-status in OCSCC seems irrelevant for clinical management.</p
Untangling introductions and persistence in COVID-19 resurgence in Europe
No full textAfter the first wave of SARS-CoV-2 infections in spring 2020, Europe experienced a resurgence of the virus starting in late summer 2020 that was deadlier and more difficult to contain1. Relaxed intervention measures and summer travel have been implicated as drivers of the second wave2. Here we build a phylogeographical model to evaluate how newly introduced lineages, as opposed to the rekindling of persistent lineages, contributed to the resurgence of COVID-19 in Europe. We inform this model using genomic, mobility and epidemiological data from 10 European countries and estimate that in many countries more than half of the lineages circulating in late summer resulted from new introductions since 15 June 2020. The success in onward transmission of newly introduced lineages was negatively associated with the local incidence of COVID-19 during this period. The pervasive spread of variants in summer 2020 highlights the threat of viral dissemination when restrictions are lifted, and this needs to be carefully considered in strategies to control the current spread of variants that are more transmissible and/or evade immunity. Our findings indicate that more effective and coordinated measures are required to contain the spread through cross-border travel even as vaccination is reducing disease burden.</p
Dynamics of the complex food environment underlying dietary intake in low-income groups
No full textBackground: Inequalities in obesity pertain in part to differences in dietary intake in different socioeconomic groups. Examining the economic, social, physical and political food environment of low-income groups as a complex adaptive system – i.e. a system of multiple, interconnected factors exerting non-linear influence on an outcome, can enhance the development and assessment of effective policies and interventions by honouring the complexity of lived reality. We aimed to develop and apply novel causal loop diagramming methods in order to construct an evidence-based map of the underlying system of environmental factors that drives dietary intake in low-income groups. Methods: A systematic umbrella review was conducted on literature examining determinants of dietary intake and food environments in low-income youths and adults in high/upper-middle income countries. Information on the determinants and associations between determinants was extracted from reviews of quantitative and qualitative studies. Determinants were organised using the Determinants of Nutrition and Eating (DONE) framework. Associations were synthesised into causal loop diagrams that were subsequently used to interpret the dynamics underlying the food environment and dietary intake. The map was reviewed by an expert panel and systems-based analysis identified the system paradigm, structure, feedback loops and goals. Results: Findings from forty-three reviews and expert consensus were synthesised in an evidence-based map of the complex adaptive system underlying the food environment influencing dietary intake in low-income groups. The system was interpreted as operating within a supply-and-demand, economic paradigm. Five sub-systems (‘geographical accessibility’, ‘household finances’, ‘household resources’, ‘individual influences’, ‘social and cultural influences’) were presented as causal loop diagrams comprising 60 variables, conveying goals which undermine healthy dietary intake. Conclusions: Our findings reveal how poor dietary intake in low-income groups can be presented as an emergent property of a complex adaptive system that sustains a food environment that increases the accessibility, availability, affordability and acceptability of unhealthy foods. In order to reshape system dynamics driving unhealthy food environments, simultaneous, diverse and innovative strategies are needed to facilitate longer-term management of household finances and socially-oriented practices around healthy food production, supply and intake. Ultimately, such strategies must be supported by a system paradigm which prioritises health.</p
Efficacy thresholds for clinical trials with advanced or metastatic leiomyosarcoma patients
No full textBackground: In 2002, the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group reported well-established values for conducting phase II trials for soft-tissue sarcomas. An update is provided for leiomyosarcoma (LMS). Materials and methods: Clinical trials with advanced or metastatic LMS were identified via literature review in PubMed (published 2003–2018, ≥10 adult LMS patients). End-points were 3- and 6-month progression-free survival rates (PFSR-3m and PFSR-6m). When estimates could not be derived from publications, data requests were sent out. Treatments were classified as recommended (R-T) or non-recommended (NR-T) according to the ESMO 2018 guidelines. A random effects meta-analysis was used to pool trial-specific estimates for first-line (1L) or pre-treated (2L+) patients separately. The ESMO Magnitude of Clinical Benefit Scale was used to guide the treatment effect to target in future trials. Results: From 47 studies identified, we obtained information on 7 1L and 16 2L+ trials for 1500 LMS patients. Overall, in 1L, PFSR-3m and PFSR-6m were 74% (95% confidence interval [CI] 64–82%) and 58% (95% CI 50–66%), respectively. For 2L+, PFSR-3m was 48% (95% CI 41–54%), and PFSR-6m was 28% (95% CI 22–34%). No difference was observed between R-T and NR-T for first or later lines. Under the alternative that the true benefit amounts to a hazard ratio of 0.65, a PFSR-6m ≥70% can be considered to suggest drug activity in 1L. For 2L+, a PFSR-3m ≥62% or PFSR-6m ≥44% would suggest drug activity. Specific results are also provided for uterine LMS. Conclusions: This work provides a new benchmark for designing phase II studies for advanced or metastatic LMS.</p
Ten years follow-up of histologically benign calcifications in the breast after vacuum-assisted stereotactic biopsy (VASB)
No full textObjective: This study assessed the short-term and the long-term breast cancer rate in patients with benign histopathologic results after a vacuum-assisted stereotactic biopsy (VASB) for calcifications. Methods: In a retrospective cohort study, all consecutive patients who had a benign diagnosis after VASB to analyze breast calcifications. Data of breast cancer development at short-term (four years) and long-term follow-up was gathered. Breast cancer rates in our cohort were compared to the breast cancer incidence in the general population. Results: Of 1376 patients who underwent VASB to analyze breast calcifications, 823 had a benign histopathologic diagnosis. During short-term follow-up, eight patients developed breast cancer. During the mean long-term follow-up period of 9.3 ± 3.1 years, 22 patients were diagnosed with ipsilateral breast cancer. The incidence rate of breast cancer after benign biopsy was comparable to the rate in the general population. Conclusion: In patients with VASB-confirmed benign calcifications of the breast, we found no excess incidence of ipsilateral breast cancer during ten years follow-up. Therefore, in patients with an increased risk of breast cancer (due to a history of breast cancer or familial risk) annual mammography should be sufficient. Patients with a population-based risk may be monitored via biennial mammography by the national screening program. More frequent screening would provide no benefit.</p
Adult Saethre-Chotzen Syndrome
No full textA 35-year-old male with Saethre-Chotzen syndrome presented with severe complaints. Neuroimaging showed a Chiari-I malformation, mild ventriculomegaly, a syrinx of the wide central canal, and various cerebral vascular anomalies including a large occipital emissary vein on the right. Ultrasound of this vein confirmed blocking of the outflow-track when turning his head to the right, which also provoked the headaches and bruit. Polysomnography revealed severe positional sleep apnea with a mixed breathing pattern, the central components consisted of periodic breathing with, at times, crescendo-decrescendo reminiscent of a Cheyne-Stokes versus Biot breathing pattern, pointing to possible brain stem/pontine problems. Continuous positive airway pressure was initiated, and the patient was instructed to avoid sleeping in the right lateral position. One year later, nearly all his complaints have resolved. A questionnaire was sent to all adult Saethre-Chotzen patients in our craniofacial unit, none reported any of the severe symptoms as described by our index case.</p