Abstract The purpose of this study was to review systematically all studies that assessed the accuracy of maternal plasma fibronectin as a serum marker for early prediction of pre-eclampsia. We ...therefore assessed studies that reported on fibronectin as serum marker for pre-eclampsia before the 25th gestational week. For the selected studies, sensitivity and specificity were calculated and plotted in ROC-space. We included 12 studies, of which only 5 studies reported sufficient data to calculate accuracy estimates, such as sensitivity and specificity. These five studies reported on 573 pregnant women of whom 109 developed pre-eclampsia. At a sensitivity of at least 50%, specificities ranged between 72 and 96% for cellular fibronectin. For total fibronectin, these numbers were 42–94%. Fibronectin seems to be a promising marker for the prediction of pre-eclampsia, however, further studies are needed to determine whether the accuracy of this test is sufficient to be clinically relevant.
Background
The optimal treatment sequence for patients with rectal cancer and synchronous liver metastases remains unclear. The aim of this study was to evaluate the feasibility and effectiveness of ...short‐course pelvic radiotherapy (5 × 5 Gy) followed by systemic therapy and local treatment of all tumour sites in patients with potentially curable stage IV rectal cancer in daily practice.
Methods
This was a retrospective study performed in eight tertiary referral centres in the Netherlands. Patients aged 18 years or above with rectal cancer and potentially resectable liver ± extrahepatic metastases, treated between 2010 and 2015, were eligible. Main outcomes included full completion of treatment schedule, symptom control and survival.
Results
In total, 169 patients were included with a median follow‐up of 49·5 (95 pr cent c.i. 43·6 to 55·6) months. The completion rate for the entire treatment schedule was 65·7 per cent. Three‐year progression‐free survival and overall survival (OS) rates were 24·2 (95 per cent c.i. 16·6 to 31·6) and 48·8 (40·4 to 57·2) per cent respectively. Median OS of patients who responded well and completed the treatment schedule was 51·5 months, compared with 15·1 months for patients who did not complete the treatment (P < 0·001). Adequate symptom control of the primary tumour was achieved in 87·0 per cent of all patients.
Conclusion
Multimodal treatment leads to relief of symptoms in most patients, and is associated with good survival rates in those able to complete the schedule. Correction added on 12 February 2020, after first online publication: the Conclusion has been reworded for clarity
Antecedentes
La secuencia óptima de tratamiento en pacientes con cáncer de recto y metástasis hepáticas sincrónicas sigue sin estar clara. El objetivo de este estudio fue evaluar en la práctica diaria la viabilidad y efectividad de la radioterapia pélvica de ciclo corto (5 x 5 Gy) seguida de tratamiento sistémico y tratamiento local de todas las localizaciones del tumor primario en pacientes con cáncer de recto estadio IV potencialmente curables.
Métodos
Estudio retrospectivo realizado en ocho centros terciarios de referencia en Holanda. Se consideró elegibles a los pacientes mayores de 18 años con cáncer de recto y metástasis hepáticas ± extrahepáticas potencialmente resecables, que fueron tratados entre 2010 y 2015. Los criterios de valoración principales incluyeron la finalización completa del programa de tratamiento, el control de los síntomas y la supervivencia.
Resultados
En total se incluyeron 169 pacientes con una mediana de seguimiento de 50 meses (rango 2‐89 meses). La tasa de finalización del programa de tratamiento completo fue del 65,7%. Las tasas de supervivencia libre de progresión a 3 años y supervivencia global (overall survival, OS) fueron 24,2% (i.c. del 95% 16,6‐31,6) y 48,8% (i.c. del 95% 40,4‐57,2), respectivamente. La mediana de OS de los pacientes que respondieron bien y completaron el programa de tratamiento fue de 51,5 meses, en comparación con 15,1 meses en pacientes que no completaron el tratamiento (P < 0,001). Se logró un control adecuado de los síntomas del tumor primario en el 87,0% de todos los pacientes.
Conclusión
El tratamiento multimodal consigue paliar los síntomas en la mayoría de los pacientes y se asocia con buenas tasas de supervivencia en aquellos pacientes que pueden completar el programa.
Treatment of patients with potentially curable stage IV rectal cancer with short‐course pelvic radiotherapy followed by systemic therapy and local treatment of all tumour sites is a feasible and effective schedule. Long‐term survival was accomplished in one‐third of patients, while providing adequate symptom relief in the majority of the other patients.
Good results
Background
The mental health of dialysis patients during the COVID-19 pandemic may have been modulated by dialysis modality. Studies comparing mental health of in-center hemodialysis and peritoneal ...dialysis patients during the first 2 years of the pandemic are lacking.
Methods
We conducted repeated cross-sectional and multivariable regression analyses to compare the mental health of in-center hemodialysis and peritoneal dialysis patients from March 2019 until August 2021 using data from the Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes. The study period was divided into one pre-pandemic and six 3-month pandemic periods (period 1–period 6). Mental health was assessed with the Mental Component Summary score of the 12-item Short Form health survey and mental symptoms of the Dialysis Symptom Index.
Results
We included 1274 patients (968 on in-center hemodialysis and 306 on peritoneal dialysis). Mental Component Summary scores did not differ between in-center hemodialysis and peritoneal dialysis patients. In contrast, in-center hemodialysis patients more often reported nervousness during period 3 (27% vs 15%,
P
= 0.04), irritability and anxiety during period 3 (31% vs 18%,
P
= 0.03, 26% vs. 9%,
P
= 0.002, respectively) and period 4 (34% vs 22%,
P
= 0.04, 22% vs 11%,
P
= 0.03, respectively), and sadness in period 4 (38% vs 26%,
P
= 0.04) and period 5 (37% vs 22%,
P
= 0.009). Dialysis modality was independently associated with mental symptoms.
Conclusions
In-center hemodialysis patients more often experienced mental symptoms compared to peritoneal dialysis patients from September 2020 to June 2021, which corresponds to the second lockdown of the COVID-19 pandemic. Mental health-related quality-of-life did not differ between in-center hemodialysis and peritoneal dialysis patients.
Trial registration number
Netherlands Trial Register NL6519, date of registration: 22 August, 2017.
Graphical abstract
Background
Dialysis is associated with frequent hospitalisations. Studies comparing hospitalisations between peritoneal dialysis (PD) and haemodialysis (HD) report conflicting results and mostly ...analyse data of patients that remain on their initial dialysis modality. This cohort study compares hospitalisations between PD and HD patients taking into account transitions between modalities.
Methods
The Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes collected hospitalisation data of patients who started dialysis between 2012 and 2017. Primary outcome was hospitalisation rate, analysed with a multi‐state model that attributed each hospitalisation to the current dialysis modality.
Results
In total, 695 patients (252 PD, 443 HD) treated in 31 Dutch hospitals were included. The crude hospitalisation rate for PD was 2.3 ( ± 5.0) and for HD 1.4 ( ± 3.2) hospitalisations per patient‐year. The adjusted hazard ratio for hospitalisation rate was 1.1 (95%CI 1.02–1.3) for PD compared with HD. The risk for first hospitalisation was 1.3 times (95%CI 1.1–1.6) higher for PD compared with HD during the first year after dialysis initiation. The number of hospitalisations and number of hospital days per patient‐year were significantly higher for PD. The most common causes of PD and HD hospitalisations were peritonitis (23%) and vascular access‐related problems (33%).
Conclusion
PD was associated with higher hospitalisation rate, higher risk for first hospitalisation and higher number of hospitalisations compared with HD. Since the PD hospitalisations were mainly caused by peritonitis, more attention to infection prevention is necessary for reducing the number of hospitalisations in the future.
We simulated the effects of the 21 August 2017 total solar eclipse on the ionosphere‐thermosphere system with the Global Ionosphere Thermosphere Model (GITM). The simulations demonstrate that the ...horizontal neutral wind modifies the eclipse‐induced reduction in total electron content (TEC), spreading it equatorward and westward of the eclipse path. The neutral wind also affects the neutral temperature and mass density responses through advection and the vertical wind modifies them further through adiabatic heating/cooling and compositional changes. The neutral temperature response lags behind totality by about 35 min, indicating an imbalance between heating and cooling processes during the eclipse, while the ion and electron temperature responses have almost no lag, indicating they are in quasi steady state. Simulated ion temperature and vertical drift responses are weaker than observed by the Millstone Hill Incoherent Scatter Radar, while simulated reductions in electron density and temperature are stronger. The model misses the observed posteclipse enhancement in electron density, which could be due to the lack of a plasmasphere in GITM. The simulated TEC response appears too weak compared to Global Positioning System TEC measurements, but this might be because the model does not include electron content above 550‐km altitude. The simulated response in the neutral wind after the eclipse is too weak compared to Fabry Perot interferometer observations in Cariri, Brazil, which suggests that GITM recovers too quickly after the eclipse. This could be related to GITM heating processes being too strong and electron densities being too high at low latitudes.
Key Points
Neutral winds modify the geographical distribution and character of responses in electron density, ion temperature, and electron temperature
Neutral winds modify the lags of neutral temperature and mass density responses with respect to totality
Comparisons with observations reveal some model deficiencies that should be addressed in future work
Background. Pre‐eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early prediction of pre‐eclampsia may be used to target high‐risk women for effective preventative ...treatments. Hyperuricemia is associated with pre‐eclampsia and it has been tested in early pregnancy for its ability to predict the later onset of the disease.
Objective. To systematically review the accuracy of determining serum uric acid before the 25th gestational week in predicting pre‐eclampsia.
Methods. We searched Medline, Embase, Cochrane Library, Medion, bibliographies of review articles and eligible primary studies, and contacted experts in the field. Language restrictions were not applied. Reviewers working independently selected studies, extracted data and assessed validity according to eight criteria. Sensitivities and specificities were plotted in a Receiver Operating Characteristic plot.
Results. We identified five primary articles, with a total of 572 women, including 44 who developed pre‐eclampsia. Study populations differed clinically, with incidences ranging from 3.4% to 40.1%. Sensitivity ranged from 0.0% to 55.6% and specificity ranged from 76.9% to 94.9%. Clinical heterogeneity and poor reporting precluded sensible pooling of data. In particular, consecutive entry of eligible women, blind assessment of the reference standard, and treatment to prevent pre‐eclampsia were poorly reported.
Conclusion. Contrary to previous reviews, we conclude that there is currently insufficient evidence to draw firm conclusions about the accuracy of serum uric acid determination in predicting pre‐eclampsia.
More than 6200 End Stage Renal Disease patients in the Netherlands are dependent on dialysis, either performed at home or in a dialysis centre. Visiting a dialysis centre three times a week is ...considered a large burden by many patients. However, recent data regarding the effects of dialysis at home on quality of life, clinical outcomes, and costs compared with in-centre haemodialysis are lacking.
The Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO) is a nationwide, prospective, observational cohort study that will include adult patients starting with a form of dialysis. Health-related quality of life, as the primary outcome, clinical outcomes and costs, as secondary outcomes, will be measured every 3-6 months in patients on home dialysis, and compared with a control group consisting of in-centre haemodialysis patients. During a 3-year period 800 home dialysis patients (600 peritoneal dialysis and 200 home haemodialysis patients) and a comparison group of 800 in-centre haemodialysis patients will be included from 53 Dutch dialysis centres (covering 96% of Dutch centres) and 1 Belgian dialysis centre (covering 4% of Flemish centres).
DOMESTICO will prospectively investigate the effect of home dialysis therapies on health-related quality of life, clinical outcomes and costs, in comparison with in-centre haemodialysis. The findings of this study are expected to ameliorate the shared decision-making process and give more guidance to healthcare professionals, in particular to assess which type of patients may benefit most from home dialysis.
The DOMESTICO study is registered with the National Trial Register on (number: NL6519 , date of registration: 22 August 2017) and the Central Committee on Research Involving Human Subjects (CCMO) (number: NL63277.029.17).
Background: Use of age‐adjusted reference values is crucial for correct diagnosis and management of thrombotic and hemorrhagic disease in children. They vary with utilized reagents and analyzers.
...Objectives: We established reference values with the Sysmex CA‐1500 System and in parallel with the Behring BCS System using reagents from Siemens Healthcare Diagnostics Products GmbH.
Methods: After informed consent, blood samples were obtained from 218 healthy children and 52 healthy adults, grouped as 1–6 months (n = 29), 7–12 months (n = 25), 1–5 years (n = 57), 6–10 years (n = 57), 11–18 years (n = 50) and > 19 years (n = 52).
Results: Most coagulation parameters demonstrate good comparability between analyzers with the exception of PT and APTT. Single coagulation factors fibrinogen, factor (F) II, FIX, FXI and XII were significantly decreased in the youngest children; the strongest age dependency was found for coagulation inhibitors Protein C and S, both significantly decreased in infancy and young childhood. We confirmed that high levels of von Willebrand factor are found in the youngest children without increased levels of FVIII followed by decreased von Willebrand levels in the subsequent age group. In children with blood group O a less distinct increase in time was found, compared with individuals with one of the other blood groups.
Conclusions: The correlation between the CA‐1500 and the BCS system was remarkable. Differences were most pronounced between children < 12 months and older children and adults, confirming the phenomenon of developmental hemostasis. The rationale for age‐related changes in the hemostatic system remains unraveled. Our results underline the need for age‐specific reference ranges.
Essentials
It is unclear whether there are differences between von Willebrand factor (VWF) activity assays.
We compared the four most used VWF activity assays in 661 von Willebrand disease (VWD) ...patients.
All assays correlated excellently, but a discrepant classification was seen in 20% of patients.
Differences between VWF activity assays have a large impact on the classification of VWD.
Summary
Background
Measuring the ability of von Willebrand factor (VWF) to bind to platelets is crucial for the diagnosis and classification of von Willebrand disease (VWD). Several assays that measure this VWF activity using different principles are available, but the clinical relevance of different assay principles is unclear.
Objective
To compare the four most widely used VWF activity assays in a large VWD patient population.
Methods
We measured VWF:RCo (ristocetin to activate VWF + whole platelets), VWF:GPIbR (ristocetin + platelet glycoprotein Ib receptor GPIb fragments), VWF:GPIbM (gain‐of‐function GPIb fragments that bind VWF spontaneously without ristocetin) and VWF:Ab (monoclonal antibody directed against the GPIb binding epitope of VWF to mimic platelets) in 661 VWD patients from the nationwide ‘Willebrand in the Netherlands’ (WiN) Study.
Results
All assays correlated excellently (Pearson r > 0.9), but discrepant results led to a different classification for up to one‐fifth of VWD patients. VWF:RCo was not sensitive enough to classify 18% of patients and misclassified half of genotypic 2B VWD patients, especially those with p.Arg1306Trp. VWF:GPIbR was more sensitive, accurately classified the vast majority of patients, and was unaffected by the p.Asp1472His variant that causes artificially low VWF:RCo. VWF:GPIbM was the most precise assay but misclassified over a quarter of genotypic 2A, 2B and 3 patients. VWF:Ab, often not considered an actual VWF activity assay, performed at least equally to the other assays with regard to accurate VWD classification.
Conclusion
Although the different VWF activity assays are often considered similar, differences between assays have a large impact on the classification of VWD.
Numerous biophysical techniques such as magnetic tweezers, flow stretching assays, or tethered particle motion assays rely on the tracking of spherical beads to obtain quantitative information about ...the individual biomolecules to which these beads are bound. The determination of these beads' coordinates from video-based images typically forms an essential component of these techniques. Recent advances in camera technology permit the simultaneous imaging of many beads, greatly increasing the information that can be captured in a single experiment. However, computational aspects such as frame capture rates or tracking algorithms often limit the rapid determination of such beads' coordinates. Here, we present a scalable and open source software framework to accelerate bead localization calculations based on the CUDA parallel computing framework. Within this framework, we implement the Quadrant Interpolation algorithm in order to accurately and simultaneously track hundreds of beads in real time using consumer hardware. In doing so, we show that the scatter derived from the bead tracking algorithms remains close to the theoretical optimum defined by the Cramer-Rao Lower Bound. We also explore the trade-offs between processing speed, size of the region-of-interests utilized, and tracking bias, highlighting in passing a bias in tracking along the optical axis that has previously gone unreported. To demonstrate the practical application of this software, we demonstrate how its implementation on magnetic tweezers can accurately track (with ∼1 nm standard deviation) 228 DNA-tethered beads at 58 Hz. These advances will facilitate the development and use of high-throughput single-molecule approaches.
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