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Background and objectives Primary lateral sclerosis (PLS) is a motor neuron disease characterised by loss of the upper motor neurons. Most patients present with slowly progressive spasticity of the legs, which may also spread to the arms or bulbar regions. It is challenging to distinguish between PLS, early-stage amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia (HSP). The current diagnostic criteria advise against extensive genetic testing. This recommendation is, however, based on limited data. Methods We aim to genetically characterize a PLS cohort using whole exome sequencing (WES) for genes associated with ALS, HSP, ataxia and movement disorders (364 genes) and C9orf72 repeat expansions. Patients fulfilling the definite PLS criteria by Turner et al. and with available DNA samples of sufficient quality were recruited from an on-going, population-based epidemiological study. Genetic variants were classified according to the ACMG criteria and assigned to groups based on disease association. Results WES was performed in 139 patients and the presence of repeat expansions in C9orf72 was analysed separately in 129 patients. This resulted in 31 variants of which 11 were (likely) pathogenic. (Likely) pathogenic variants resulted in 3 groups based on disease association: ALS-FTD (C9orf72, TBK1), pure HSP (SPAST, SPG7), “ALS-HSP-CMT overlap” (FIG4, NEFL, SPG11). Discussion In a cohort of 139 PLS patients, genetic analyses resulted in 31 variants (22%) of which 10 (7%) (likely) pathogenic associated with different diseases (predominantly ALS and HSP). Based on these results and the literature, we advise to consider genetic analyses in the diagnostic work-up for PLS.

ObjectiveThe Comprehensive Complication Index (CCI) is an instrument used to measure cumulative post-operative complications. Our study aimed to validate the CCI after cytoreductive surgery for primary advanced-stage epithelial ovarian cancer, and to compare its diagnostic performance with the Clavien-Dindo classification.MethodsThis prospective cohort study classified post-operative complications according to the Clavien-Dindo classification and the CCI. Logistic regression was used to determine the association between both classifications with intensive care unit admission, prolonged length of hospital stay (defined as stays longer than the 75th percentile of all stays in this study), 30-day readmission, and time to initiating chemotherapy after surgery >42 days. Area under the receiver operating characteristic curves (AUC) were used to assess the discriminative performance of each classification.ResultsA total of 300 patients were included in the analysis. Most patients (n=255, 85%) underwent interval cytoreductive surgery. Complete cytoreduction was achieved in 235 (78%) patients. Overall, 30-day post-operative complications classified by the Clavien-Dindo classification occurred in 147 (49%) patients. Severe complications (grade ≥3a) occurred in 51 (17%) patients. Approximately 30% (n=82) had multiple complications. The CCI showed an excellent correlation with the Clavien-Dindo classification (r=0.906, p42 days (all pConclusionsBoth the Clavien-Dindo classification and CCI showed significant associations with all surgical outcomes. However, the cumulative complications score of the CCI demonstrated a more superior discriminative performance than the Clavien-Dindo classification for prolonged length of hospital stay in advanced-stage epithelial ovarian cancer.

Background The aim of surgery for advanced-stage ovarian cancer is a complete cytoreduction, because this is the most important independent prognostic factor for prolonged survival. Yet this can be difficult to achieve when there are micrometastases on the intestinal mesentery or intestines. The PlasmaJet device is an instrument to remove these micrometastases, but little is known about the depth of damage in human tissue compared to electrocoagulation devices. Methods A prospective study was performed for the ex-vivo comparison of the histological depth of thermal damage of neutral argon plasma (PlasmaJet®) and electrocoagulation devices, in a series of 106 histological slides of 17 advanced-stage ovarian cancer patients. Depending on the tissue types resected during complete cytoreductive surgery, samples were collected from reproductive organs (uterus, ovaries), intestines (ileum, colon, rectum) and omentum, intestinal mesentery and peritoneum. Results Average thermal damage depth was 0.15 mm (range 0.03–0.60 mm) after use of neutral argon plasma and 0.33 mm (range 0.08–1.80 mm) after use of electrocoagulation (p Conclusion Our case series suggests that the use of neutral argon plasma during cytoreductive surgery produces significantly less thermal damage than electrocoagulation treatment. It is therefore considered a thermally safe alternative, aiding in the achievement of cytoreductive surgery.

Inspired by recent technological advances in the gaming industry, we used capture cards to create and LIVE-stream high quality 3D-images. With this novel technique, we developed a real-life stereoscopic 3D full-body illusion paradigm (3D projection). Unlike previous versions of the full-body illusion that rely upon unwieldy head-mounted displays, this paradigm enables the unobstructed investigation of such illusions with neuroscience methods (e.g., transcranial direct current stimulation, transcranial magnetic stimulation, electroencephalography, and near-infrared spectroscopy) and examination of their neural underpinnings. This paper has three aims: (i) to provide a step-by-step guide on how to implement 3D LIVE-streaming, (ii) to explain how this can be used to create a full-body illusion paradigm; and (iii) to present evidence that documents the effectiveness of our methods (de Boer et al., 2020), including suggestions for potential applications. Particularly significant is the fact that 3D LIVE-streaming is not GPU-intensive and can easily be applied to any device or screen that can display 3D images (e.g., TV, tablet, mobile phone). Therefore, these methods also have potential future clinical and commercial benefits. 3D LIVE-streaming could be used to enhance future clinical observations or educational tools, or potentially guide medical interventions with real-time high-quality 3D images. Alternatively, our methods can be used in future rehabilitation programs to aid recovery from nervous system injury (e.g., spinal cord injury, brain damage, limb loss) or in therapies aimed at alleviating psychosis symptoms. Finally, 3D LIVE-streaming could set a new standard for immersive online gaming as well as augmenting online and mobile experiences (e.g., video chat, social sharing/events).

Medical use of (non-)thermal plasmas is an emerging field in gynaecology. However, data on plasma energy dispersion remain limited. This systematic review presents an overview of plasma devices, fields of effective application, and impact of use factors and device settings on tissues in the female pelvis, including the uterus, ovaries, cervix, vagina, vulva, colon, omentum, mesenterium, and peritoneum. A search of the literature was performed on 4 January 2023 in the Medline Ovid, Embase, Cochrane, Web of Science, and Google Scholar databases. Devices were classified as plasma-assisted electrosurgery (ES) using electrothermal energy, neutral argon plasma (NAP) using kinetic particle energy, or cold atmospheric plasma (CAP) using non-thermal biochemical reactions. In total, 8958 articles were identified, of which 310 were scanned, and 14 were included due to containing quantitative data on depths or volumes of tissues reached. Plasma-assisted ES devices produce a thermal effects depth of

Background Pulmonary artery (PA) dilatation is often seen in pulmonary hypertension (PH) and is considered a long-term consequence of elevated pressure. The PA dilates over time and therefore may reflect disease severity and duration. Survival is related to the stage of the disease at the time of diagnosis and therefore PA diameter might be used to predict prognosis. This study evaluates the outcome of patients with pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension (CTEPH) and investigates whether PA diameter at the time of diagnosis is associated with mortality. Methods Patients visiting an outpatient clinic of a tertiary centre between 2004 and 2018 with a cardiac catheterisation confirmed diagnosis of PAH or CTEPH and a CT scan available for PA diameter measurement were included. PA diameter and established predictors of survival were collected (New York Heart Association (NYHA) class, N‑terminal pro-brain natriuretic peptide (NT-proBNP) level and 6‑min walking distance (6MWD)). Results In total 217 patients were included (69% female, 71% NYHA class ≥III). During a median follow-up of 50 (22–92) months, 54% of the patients died. Overall survival was 87% at 1 year, 70% at 3 years and 58% at 5 years. The mean PA diameter was 34.2 ± 6.2 mm and was not significantly different among all the diagnosis groups. We found a weak correlation between PA diameter and mean PA pressure ( r = 0.23, p Conclusion The prognosis of PAH and CTEPH is still poor. Known predictors of survival were confirmed, but PA diameter at diagnosis was not associated with survival in PAH or CTEPH patients.

While there is great interest in polymer nanofibers due to their high strength, methods to measure their time-temperature superposition (TTS) curves are lacking. The objective of this work is to demonstrate one such method and thereby to predict room temperature creep compliance over many decades of time. A complimentary measurement is also presented to estimate the associated activation energy. The experimental method is demonstrated for polyacrylonitrile (PAN) nanofibers using an on-chip surface micromachined stepper motor actuator. It is first shown that the method yields good agreement with previous room temperature measurements. Subsequently, data up to 95 °C, near the glass transition temperature, is presented. Time-temperature superposition master curves are then constructed, and activation energies for two narrow diameter ranges (221 ± 27 nm and 150 ± 9 nm) are determined. The activation energy of the 221 nm fiber agrees well with the bulk PAN value, while the 150 nm fiber is 50% larger, indicating the importance of higher chain packing and reduced chain mobility in thinner fibers. TTS curves spanning 7 (221 nm) and 9 (150 nm) decades are presented. Over this time span the creep compliance increases by a factor of approximately 10 for each. This work demonstrates a viable method to measure polymer nanofiber TTS curves from which quantitative activation energy can be determined, and from which creep compliance values over time can be predicted.

Objective: To determine the risk of overall preterm birth (PTB) and spontaneous PTB in a pregnancy after a caesarean section (CS) at term. Design: Longitudinal linked national cohort study. Setting: The Dutch Perinatal Registry (1999–2009). Population: 268 495 women with two subsequent singleton pregnancies were identified. Methods: A cohort study based on linked registered data from two subsequent pregnancies in the Netherlands. Main outcome measures: The incidence of overall PTB and spontaneous PTB with subgroup analysis on gestational age at first delivery and type of CS (planned or unplanned). Results: Of 268 495 women with a singleton first pregnancy who delivered at term, 15.76% (n = 42 328) had a CS. The incidence of PTB in the second pregnancy was 2.79% (n = 1182) in women with a previous CS versus 2.46% (n = 5570) in women with a previous vaginal delivery (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 1.07–1.21). This increased risk is mainly driven by an increased risk of spontaneous PTB after previous CS at term (aOR 1.50, 95% CI 1.38–1.70). Analysis for type of CS compared with vaginal delivery showed an aOR on spontaneous PTB of 1.86 (95% CI 1.58–2.18) for planned CS and an aOR of 1.40 (95% CI 1.24–1.58) for unplanned CS. Conclusions: CS at term is associated with a marginally increased risk of spontaneous PTB in a subsequent pregnancy. Tweetable abstract: Caesarean section at term is associated with a marginally increased risk of spontaneous PTB in a subsequent pregnancy.

Objective To assess the cost-effectiveness of treatment with nifedipine compared with atosiban in women with threatened preterm birth. Design An economic analysis alongside a randomised clinical trial (the APOSTEL III study). Setting Obstetric departments of 12 tertiary hospitals and seven secondary hospitals in the Netherlands and Belgium. Population Women with threatened preterm birth between 25 and 34 weeks of gestation, randomised for tocolysis with either nifedipine or atosiban. Methods We performed an economic analysis from a societal perspective. We estimated costs from randomisation until discharge. Analyses for singleton and multiple pregnancies were performed separately. The robustness of our findings was evaluated in sensitivity analyses. Main outcome measures Mean costs and differences were calculated per woman treated with nifedipine or atosiban. Health outcomes were expressed as the prevalence of a composite of adverse perinatal outcomes. Results Mean costs per patients were significantly lower in the nifedipine group [singleton pregnancies: euro34,897 versus euro43,376, mean difference (MD) -euro8479 [95% confidence interval (CI) -euro14,327 to -euro2016)]; multiple pregnancies: euro90,248 versus euro102,292, MD -euro12,044 (95% CI -euro21,607 to euro -1671). There was a non-significantly higher death rate in the nifedipine group. The difference in costs was mainly driven by a lower neonatal intensive care unit admission (NICU) rate in the nifedipine group. Conclusion Treatment with nifedipine in women with threatened preterm birth results in lower costs when compared with treatment with atosiban. However, the safety of nifedipine warrants further investigation. Tweetable abstract In women with threatened preterm birth, tocolysis using nifedipine results in lower costs when compared with atosiban.

In order to avoid pedicle screw misplacement in posterior spinal deformity surgery, patient specific 3D‑printed guides can be used. An accuracy assessment of pedicle screw insertion can be obtained by superimposing CT-scan images from a preoperative plan over those of the postoperative result. The aim of this study is to report on the accuracy of drill guide assisted pedicle screw placement in thoracolumbar spinal deformity surgery by means of a superimpose CT-analysis.Concomitant with the clinical introduction of a new technique for drill guide assisted pedicle screw placement, the accuracy of pedicle screw insertion was analyzed in the first patients treated with this technique by using superimpose CT-analysis. Deviation from the planned ideal intrapedicular screw trajectory was classified according to the Gertzbein scale.Superimpose CT-analysis of 99 pedicle screws in 5 patients was performed. The mean linear deviation was 0.92 mm, the mean angular deviation was 2.92° with respect to the preoperatively planned pedicle screw trajectories. According to the Gertzbein scale, 100% of screws were found to be positioned within the "safe zone".The evaluated patient specific 3D-printed guide technology was demonstrated to constitute a safe and accurate tool for precise pedicle screw insertion in spinal deformity surgeries. Superimpose CT-analysis showed a 100% accuracy of pedicle screw placement without any violation of the pedicle wall or other relevant structures. We recommend a superimpose CT-analysis for the first consecutive patients when introducing new technologies into daily clinical practice, such as intraoperative imaging, navigation or robotics.

Background Azathioprine and mercaptopurine exposure during conception and pregnancy has been considered safe in patients with inflammatory bowel disease (IBD). Its use is not associated with a higher risk of preterm birth or low birthweight. Data on the safety of tioguanine, an alternative thiopurine-derivate, in pregnant IBD patients is limited. In a small case series, tioguanine appeared safe for both mother and fetus. In this study, we describe the teratogenicity and safety of tioguanine during pregnancy in a large group of IBD patients. Methods We performed a preliminary analysis of our ongoing multicenter descriptive case series of female IBD patients who were treated with tioguanine at some point during their pregnancy. Data regarding disease and medication history, pregnancy course and neonatal outcomes, such as preterm birth, miscarriage, birthweight, Apgar scores and congenital abnormalities were collected by the treating physician. Results Seventy-three pregnancies, including three twin pregnancies were collected. Most women (80%) had Crohn’s disease and the mean age during delivery was 31 years (range 21-42). Tioguanine was used throughout the entire pregnancy in 89% with a median daily dose of 20 mg. Five (6.8%) of these pregnancies resulted in a miscarriage, all within the first 13 weeks. No congenital abnormalities were reported in all seventy-one live born children. In the singleton pregnancies the median birthweight was 3375 gram (IQR 3075-3739, N=61, 4 missing values) with a median gestational age of 39.0 weeks (IQR 38.3-40.0, N=61). Four children (6.5%) were born prematurely ( The median Apgar score after 1 and 5 minutes was respectively 9 (IQR 8-9, N=58) and 10 (IQR 9-10, N=59). Two neonates (3.4%), one born pre-and dysmature and the other a premature second-born twin, had an Apgar score ( Conclusion In this large case-series, tioguanine exposure during pregnancy was not associated with an increased risk of congenital abnormalities, low birthweight or preterm birth in IBD patients. These data support the safe use of tioguanine during pregnancy in IBD.

Hyponatraemia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) can pose a therapeutic challenge. After fluid restriction, urea is recommended as a second-line treatment by Dutch and European treatment guidelines. Data on this practice are still scarce. We introduced urea for the treatment of SIADH in our hospital and prospectively collected data on its effectiveness and tolerability.In hospitalised patients with a serum sodium level ≤ 129 mmol/l due to SIADH, urea in a dosage of 0.25-0.50 g/kg/day was indicated if prescribed fluid restriction had no effect or could not be applied. Measurement of serum sodium was performed at baseline, after the first and second day of urea therapy and at the end of the first inpatient treatment episode (EIT). The primary outcomes were normonatraemia (serum sodium level 135-145 mmol/l) at EIT and discontinuation of urea due to side effects.Thirteen patients were treated with urea over a median of 5 days (range 2-10 days). The median serum sodium level at baseline was 124 mmol/l (IQR 122-128), which increased to 128 mmol/l (IQR 123-130) (p = 0.003) after the first dose of urea and to 130 mmol/l (IQR 127-133) (p = 0.002) after the second dose of urea. Normonatraemia at EIT was observed in 8 (62%) patients. Seven (54%) patients reported distaste. In one of these patients, urea was discontinued because of nausea. Overcorrection was not observed.Our data show that urea is an effective treatment for hospitalised patients with SIADH. Distaste was a frequent side effect, but usually did not lead to early treatment discontinuation.

Limited evidence supports the efficacy of antimicrobial prophylaxis (AP) in prevention of gunshot woundrelated (GSW-related) infection in resource restricted areas. At Tygerberg Hospital, South Africa, it is standard care for GSW patients to receive one dose of broad-spectrum AP. For various reasons, this protocol is not consistently followed. This study aimed to assess the efficacy of AP in the reduction of in-hospital GSW-related infection and to identify opportunities for practice improvement.All patients admitted with GSW over a three-month period were eligible for inclusion. Patients who did and did not receive AP were identified retrospectively the morning of admission; thereafter, data was collected prospectively. Data regarding circumstances of the incident, injury characteristics, type of AP and surgery was obtained. The occurrence of in-hospital GSW-related infection was recorded over 30 days or until discharge. Propensity score matching (PSM) and inverse probability weighting (IPW) methods were utilised to assess the effect of AP on the prevention of GSW-related infection.165 consecutive patients were assessed, of which 103 received AP according to protocol within 12 hours of admission. PSM showed a reduced in-hospital GSW infection risk of 12% (95% CI, 0.2-24%,Providing AP to GSW patients in a civilian setting appeared to result in a modest but clinically relevant lower risk of in-hospital GSW-related infection. In this study setting, optimisation of AP for all patients with GSWs should significantly lower the burden of wound infection.

Background Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit. Methods This was a nationwide study in the Netherlands. All liver resections reported in the Dutch Hepato Biliary Audit between 2014 and 2017 were included. Annual centre volume was calculated and classified in categories of 20 procedures per year. Main outcomes were major morbidity (Clavien–Dindo grade IIIA or higher) and 30‐day or in‐hospital mortality. Results A total of 5590 liver resections were done across 34 centres with a median annual centre volume of 35 (i.q.r. 20–69) procedures. Overall major morbidity and mortality rates were 11·2 and 2·0 per cent respectively. The mortality rate was 1·9 per cent after resection for colorectal liver metastases (CRLMs), 1·2 per cent for non‐CRLMs, 0·4 per cent for benign tumours, 4·9 per cent for hepatocellular carcinoma and 10·3 per cent for biliary tumours. Higher‐volume centres performed more major liver resections, and more resections for hepatocellular carcinoma and biliary cancer. There was no association between hospital volume and either major morbidity or mortality in multivariable analysis, after adjustment for known risk factors for adverse events. Conclusion Hospital volume and postoperative outcomes were not associated., This study analysed the association between hospital volume and postoperative outcomes in the nationwide Dutch Hepato Biliary Audit. A total of 5590 resections was performed across 34 centres with a median annual centre volume of 35 (i.q.r. 20–69) procedures. No association was found between hospital and postoperative outcomes. Cut‐off about right

Actuation of a highly scalable phase change mechanical relay is demonstrated for the first time. The Phase Change NEMS Relay (PCNR) is a non-volatile relay based on the mechanical expansion of GeTe phase change material. On state resistance was demonstrated to be ~260 Ω and an off state leakage as low as 20 fA was recorded. Switching on and off delay times were demonstrated to be 300 ns and 600 ns, respectively. Scaling analysis shows a path towards 20 nm × 5 nm size devices with an actuation voltage and energy of 500 mV and 70 fJ, respectively.

Background Mortality rates are high among hospitalized patients with COVID-19, especially in those intubated on the ICU. Insight in pathways associated with unfavourable outcome may lead to new treatment strategies. Methods We performed a prospective cohort study of patients with COVID-19 admitted to general ward or ICU who underwent serial blood sampling. To provide insight in the pathways involved in disease progression, associations were estimated between outcome risk and serial measurements of 64 biomarkers in potential important pathways of COVID-19 infection (inflammation, tissue damage, complement system, coagulation and fibrinolysis) using joint models combining Cox regression and linear mixed-effects models. For patients admitted to the general ward, the primary outcome was admission to the ICU or mortality (unfavourable outcome). For patients admitted to the ICU, the primary outcome was 12-week mortality. Findings A total of 219 patients were included: 136 (62%) on the ward and 119 patients (54%) on the ICU; 36 patients (26%) were included in both cohorts because they were transferred from general ward to ICU. On the general ward, 54 of 136 patients (40%) had an unfavourable outcome and 31 (23%) patients died. On the ICU, 54 out of 119 patients (45%) died. Unfavourable outcome on the general ward was associated with changes in concentrations of IL-6, IL-8, IL-10, soluble Receptor for Advanced Glycation End Products (sRAGE), vascular cell adhesion molecule 1 (VCAM-1) and Pentraxin-3. Death on the ICU was associated with changes in IL-6, IL-8, IL-10, sRAGE, VCAM-1, Pentraxin-3, urokinase-type plasminogen activator receptor, IL-1-receptor antagonist, CD14, procalcitonin, tumor necrosis factor alfa, tissue factor, complement component 5a, Growth arrest–specific 6, angiopoietin 2, and lactoferrin. Pathway analysis showed that unfavourable outcome on the ward was mainly driven by chemotaxis and interleukin production, whereas death on ICU was associated with a variety of pathways including chemotaxis, cell-cell adhesion, innate host response mechanisms, including the complement system, viral life cycle regulation, angiogenesis, wound healing and response to corticosteroids. Interpretation Clinical deterioration in patients with severe COVID-19 involves multiple pathways, including chemotaxis and interleukin production, but also endothelial dysfunction, the complement system, and immunothrombosis. Prognostic markers showed considerable overlap between general ward and ICU patients, but we identified distinct differences between groups that should be considered in the development and timing of interventional therapies in COVID-19. Funding Amsterdam UMC, Amsterdam UMC Corona Fund, and Dr. C.J. Vaillant Fonds.

OBJECTIVE: To report pregnancy outcomes of SHiP (spontaneous haemoperitoneum in pregnancy) and the association with endometriosis.DESIGN: Retrospective case note review.SETTING: Dutch referral hospitals for endometriosis.SAMPLE: Eleven women presenting with 15 events of SHiP.METHODS: In collaboration with the Dutch Working Group on Endometriosis, unpublished cases of SHiP that occurred in the Netherlands between 2010 and 2015 were retrieved.MAIN OUTCOME MEASURES: Maternal and perinatal mortality and morbidity.RESULTS: SHiP occurred predominantly in the second and third trimester of pregnancy. The earliest and major presenting symptom was an acute onset of abdominal pain, often combined with low haemoglobin levels or signs of fetal distress. Imaging was a diagnostic tool when free peritoneal fluid could be observed. For surgical treatment of the bleeding site, a midline laparotomy was mostly needed, the median estimated amount of blood loss was 2000 mL. No fetomaternal or perinatal mortality was reported, despite a high rate of preterm births (54.5%). In all women, endometriosis was diagnosed at a certain moment in time and therefore was probably involved in the pathogenesis of SHiP. Four women showed recurrence of SHiP. In one of these cases the second event of SHiP occurred in a subsequent pregnancy.CONCLUSION: Pregnancy outcomes of SHiP are improving when compared with previous reports, with absent fetomaternal and perinatal mortality in this recent series. Growing knowledge and adequate multidisciplinary intervention may have contributed to these favourable results. Increasing awareness of this serious complication of pregnancy is advocated, especially in women diagnosed with endometriosis.TWEETABLE ABSTRACT: Growing awareness of SHiP is advocated, especially in women diagnosed with endometriosis.

BACKGROUND Red blood cell (RBC) transfusion is associated with organ failure. The mechanism remains unknown, but may include adherence of blood cells to the microvasculature. We hypothesized that RBC-derived extracellular vesicles (EVs) interact with monocytes to activate endothelial cells. STUDY DESIGN AND METHODS Human umbilical vein endothelial cells were incubated with supernatant from fresh and stored RBC units either containing EVs or depleted from EVs, with or without the addition of immune cells. We measured expression of adhesion markers by flow cytometry and markers of coagulation and inflammation in the culture medium. We studied phagocytosis of EVs by monocytes by using confocal microscopy and flow cytometry. RESULTS Incubation of endothelial cells with monocytes alone did not induce up regulation of adhesion markers. The addition of both monocytes and supernatant from RBCs containing EVs resulted in up regulation of endothelial expression of intercellular adhesion molecule 1 and E-selectin when compared to baseline. Up regulation was absent when stimulated with RBC supernatant depleted from EVs. EVs are phagocytosed by monocytes, which was partly abrogated after coincubation with two different complement receptor 3 (CR3)-blocking antibodies. Addition of RBC-derived EVs also increased levels of von Willebrand factor (VWF). There were no differences between groups related to storage time. CONCLUSION EVs from RBC transfusion bags activate monocytes with subsequent up regulation of endothelial cell adhesion markers. EVs are phagocytosed by monocytes through CR3. Furthermore, these EVs proved to be a source of VWF. These effects are unrelated to storage time. Thereby, EVs from RBC transfusion bags induce a proinflammatory and procoagulant endothelial cell response.

Within the past few decades, harmful algal blooms (HABs) have occurred frequently in Indonesian waters, resulting in environmental degradation, economic loss and human health problems. So far, HAB related studies mainly addressed ecological traits and species distribution, yet toxin measurements were virtually absent for Indonesian waters. The aim of the present study was to explore variability of the potentially toxic marine diatom genus Pseudo-nitzschia, as well as its neurotoxin domoic acid as a function of environmental conditions in Ambon Bay, eastern Indonesia. Weekly phytoplankton samples, oceanographic (CTD, nutrients) and meteorological (precipitation, wind) parameters were analyzed at 5 stations in the bay during the dry and wet seasons of 2018. Liquid chromatography – tandem mass spectrometry (LC–MS/MS) was used to detect particulate DA (pDA). Vegetative cells of Pseudo-nitzschia spp. and pDA were found in 98.6% and 51.4% of the samples, respectively. pDA levels were low, yet detected throughout the campaign, implying that Ambon Bay might potentially be subject to amnesic shellfish poisoning. The highest levels of both Pseudo-nitzschia spp. cell abundance and pDA were found in the wet season, showing a strong positive correlation between both parameters, compared to the dry season, (r = 0.87 and r = 0.66 (p

About 80 % of all women affected by ovarian cancer present with advanced stage disease at the time of diagnosis. Achieving complete cytoreduction is complicated when many small tumor spots are found. Yet, complete cytoreduction is the most important determinant of survival. Application of a thermal plasma energy device to standard surgical instruments may help achieve complete cytoreduction. The ‘PlasmaJet® Device’ (Plasma Surgical, Inc., Roswell, GA, USA) is an electrically neutral device which emits a high–energy jet of argon plasma for direct tissue effects. We performed a literature review to investigate whether the use of the ‘PlasmaJet® Device’ in surgery of advanced stage ovarian carcinoma (FIGO IIIB-IV) is effective and safe. The primary outcome was the proportion of complete cytoreductions. The secondary outcomes were: complication rate, proportion of colostomies applied, histological findings, disease-free survival and overall survival. Five case series or reports were found, including a total of 77 patients with FIGO stage IIIC-IV ovarian cancer in whom the PlasmaJet® device was used for primary or interval debulking. Complete cytoreduction was obtained in 79% of the patients. Apart from one pneumothorax after extensive surgery, but no harm or additional complications related to the use of the PlasmaJet® Device were reported. Data on disease-free survival or overall survival were not reported. These findings suggest that the PlasmaJet® Device is an efficient and safe innovative surgical device for debulking surgery with encouraging results. We have proposed an RCT in which we will compare feasibility, safety and effectiveness aspects of the use of the PlasmaJet® versus conventional electrosurgery in advanced stage epithelial ovarian cancer (FIGO IIIB-IV).

Background Twelve percent of the Dutch population consists of non-Western immigrant women with an incidence of breast cancer that has risen from 2,9% in 2005 to 5% in 2015. For the second generation of these women the incidence of breast cancer is expected to meet the native Dutch population rates soon, partly due to adoption of Western style dietary habits and physical activity. Chemotherapeutic treatment (CT) for breast cancer is associated with increased body fatness and interventions to prevent this increase are currently explored. Whether perceptions on cancer and treatment differ between non-Western immigrant women than for Dutch women needs to be evaluated before these interventions can be set up. This study aimed to explore cultural and religious differences on women's perceptions of the diagnosis of breast cancer and changes in physical activity and eating habits during chemotherapy treatment. Methods A longitudinal qualitative multiple case study was conducted. Newly diagnosed women with breast cancer were recruited and purposively selected (n=23, non-immigrant) from six hospitals in the Netherlands. Semi structured interviews were conducted three times (in total 69): before start of CT, halfway and after CT. In addition 38 women (20 non-immigrant and 18 immigrant) were recruited and interviewed after finishing CT. All interviews (n=107, from 61 women) were audiotaped and transcribed verbatim. A thematic content analysis approach was used. Results All 43 non-immigrant women, mean age 51,1 yrs. and 18 immigrant women mean age 43,2 yrs., experienced known side effects from CT. Loss of hair and sometimes the breast appeared to be especially for immigrant women a shocking experience and for some even a loss of femininity. Most of the women perceived to have received incomplete and often unclear information from hospitals about weight and CT treatment. Immigrant women participating the Ramadan during treatment encountered resistance from their physicians. Weight gain during period of CT was higher among immigrant women (mean 13,1 kg, 4-28 kg) than among non-immigrant women (mean 2,5 kg, 2-9 kg). Although both groups said to be less physically active and complained about fatigue, non-immigrant women trying to maintain daily structure and were more active with their diet than most immigrants. Immigrant women expressed cancer as a taboo in their culture impeding them to talk openly about their illness, only when side effects of CT such as hair loss were visible they found it inevitable. Cancer was associated with death at time of diagnosis. For most immigrants and a few non-immigrants this was considered a religious ordeal from Allah or God, these women perceived less influence on their behavior during treatment. Most non-religious women perceived breast cancer as bad luck, stress or heredity. Conclusion Especially immigrant women experienced little respect for their culture and insufficient information about treatment. Non-immigrants had a need to actively contribute to their treatment while this need was less obvious for immigrants. Probably because they felt not encouraged by their religion and culture. Citation Format: de Kruif AJ, Derks MJ, de Boer MR, Winkels R, Visser M, Kampman E, Westerman MJ. Cultural and religious differences during breast cancer treatment between Dutch and non-Western immigrant women. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-28.

Background: Transfusion of red blood cells (RBCs) is associated with adverse outcome, but the causative factor is unknown. Extracellular vesicles (EVs) have pro-inflammatory properties. We hypothesized that EVs released from both fresh and stored RBC products can induce a host inflammatory response in a dose-dependent manner. Methods: Whole blood was incubated with supernatant from RBC units stored for different time periods, either containing (different numbers of) EVs or depleted from EVs. Results: Incubation with both fresh and stored supernatant containing EVs induced a strong host response with production of TNF, IL-6 and IL-8. In supernatant depleted from EVs, this host response was completely abrogated. IL-10 levels were not affected. EV-induced host response was both dependent on the number of EVs as well as on storage time. Conclusions: EVs from both fresh and stored RBC units illicit a strong inflammatory host response in recipients and may therefore contribute to adverse outcome of RBC transfusion.

Information from multiple modalities contributes to recognizing emotions. While it is known interactions occur between modalities, it is unclear what characterizes these. These interactions, and changes in these interactions due to sensory impairments, are the main subject of this PhD project. This extended abstract for the Doctoral Symposium of ETRA 2018 describes the project; its background, what I hope to achieve, and some preliminary results.

Objective: This study explored the long-term impact of a Total Laryngectomy (TL) on the partner and on the relationship between laryngectomees and their partners. Methods: 151 laryngectomees and 144 partners completed questionnaires assessing the psychosocial impact of a TL on the partner (quality of life, anxiety and depression, loss of control, fear, hopelessness, post-traumatic growth, caregiving burden) and on the spousal relationship (change in the quality of the spousal relationship and openness to discussion of the illness in the family). Results: A considerable number of partners of laryngectomees experience a psychosocial impact of the consequences of the TL, specifically on their social life (35%) and on their sexual relationship (31%). Also, the tendency of other people to neglect their laryngectomized life companion, affects more than half of the partners negatively. Clinical levels of anxiety and depression were found in around 20% of the partners. The consequences of a TL has a negative change on the sexual functioning for more than 30% of both laryngectomees and partners, the communication for around one fifth of both laryngectomees and partners, and feelings of dependency of the partner for one third of the laryngectomees. Conclusions: A TL has a considerable impact on the psychosocial life of partners of laryngectomees and on the spousal relationship. The findings of this explorative study sets the stage for structural screening on the need for support, not only for patients, but also for their partners. Sexuality and intimacy should be part of this screening. (C) 2015 Elsevier Ltd. All rights reserved.

In a multiple-dose-ranging trial, we previously evaluated higher doses of rifampin in patients for 2 weeks. The objectives of the current study were to administer higher doses of rifampin for a longer period to compare the pharmacokinetics, safety/tolerability, and bacteriological activity of such regimens. In a double-blind, randomized, placebo-controlled, phase II clinical trial, 150 Tanzanian patients with tuberculosis (TB) were randomized to receive either 600 mg (approximately 10 mg/kg of body weight), 900 mg, or 1,200 mg rifampin combined with standard doses of isoniazid, pyrazinamide, and ethambutol administered daily for 2 months. Intensive pharmacokinetic sampling occurred in 63 patients after 6 weeks of treatment, and safety/tolerability was assessed. The bacteriological response was assessed by culture conversion in liquid and solid media. Geometric mean total exposures (area under the concentration-versus-time curve up to 24 h after the dose) were 24.6, 50.8, and 76.1 mg · h/liter in the 600-mg, 900-mg, and 1,200-mg groups, respectively, reflecting a nonlinear increase in exposure with the dose ( P < 0.001). Grade 3 adverse events occurred in only 2 patients in the 600-mg arm, 4 patients in the 900-mg arm, and 5 patients in the 1,200-mg arm. No significant differences in the bacteriological response were observed. Higher daily doses of rifampin (900 and 1,200 mg) resulted in a more than proportional increase in rifampin exposure in plasma and were safe and well tolerated when combined with other first-line anti-TB drugs for 2 months, but they did not result in improved bacteriological responses in patients with pulmonary TB. These findings have warranted evaluation of even higher doses of rifampin in follow-up trials. (This study has been registered at ClinicalTrials.gov under identifier NCT00760149.)

To detect the presence of bovine herpesvirus (BoHV) type 4 in New Zealand dairy cows with clinical metritis.Serum samples taken from 92 dairy cows with clinical metritis, each from a different farm, were tested for the presence of antibodies against BoHV-4 using a commercially available, indirect ELISA. Peripheral blood mononuclear cells (PBMC) were collected from 10 BoHV-4 seropositive cows, and PBMC were examined by a pan-herpesvirus nested PCR to detect herpesvirus. PCR products were sequenced directly and a proportion of the PCR products were cloned and sequenced to identify the virus present.Antibodies to BoHV-4 were detected in 23/92 (25%) serum samples. The pan-herpesvirus PCR was positive in 8/10 PBMC samples. Cloning and sequencing identified that all of the eight PCR-positive PBMC contained bovine lymphotropic herpesvirus (BLHV); no BoHV-4 DNA was detected.This study reports the finding of the presence of apparent antibodies to BoHV-4, and BLHV DNA in New Zealand dairy cows affected by metritis.Bovine herpesvirus type 4 and BLHV are reported to have the potential to cause reproduction failure in cows. This is the first report of apparent BoHV-4 antibodies, and BLHV in New Zealand. The importance and epidemiology of these viruses in cattle in New Zealand requires further investigation.

Item does not contain fulltext Severe dengue is characterised by thrombocytopenia, plasma leakage and bleeding. Platelets are important for preservation of endothelial integrity. We hypothesised that platelet activation with secondary platelet dysfunction contribute to plasma leakage. In adult Indonesian patients with acute dengue, we measured platelet activation status and the response to the platelet agonist TRAP using flow cytometer-based assays. Patients were monitored daily for plasma leakage by ultrasonography. Acute dengue was associated with platelet activation with an increased expression of the activated fibrinogen receptor (alphaIIbbeta3), the lysosomal marker CD63 and the alpha-granule marker CD62P (P-selectin). Upon maximal platelet activation by TRAP, platelet function defects were observed with a significantly reduced maximal activated alphaIIbbeta3 and CD63 expression and reduced platelet-monocyte and platelet-neutrophil complexes. Patients in the lowest tertile of activated alphaIIbbeta3 and CD63 expression had an odds ratio for plasma leakage of 5.2 (95% confidence interval [CI] 1.3-22.7) and 3.9 (95% CI 1.1-13.7), respectively, compared to the highest tertile. Platelet-derived serotonin has previously been related to plasma leakage and we found increased intra-platelet serotonin concentrations in our patients. In conclusion, platelet activation with platelet function alterations can be found in patients with acute dengue and this may contribute to dengue-associated plasma leakage.

Rare earth elements (REEs) are important for green and a large variety of high-tech technologies and are, therefore, in high demand. As a result, supply with REEs is likely to be disrupted (the degree of depends on the REE) in the near future. The 17 REEs are divided into heavy and light REEs. Other critical elements besides REEs, identified by the European Commission, are also becoming less easily available. Although there is no deficiency in the earth's crust of rare earth oxides, the economic accessibility is limited. The increased demand for REEs, the decreasing export from China, and geopolitical concerns on availability contributed to the (re)opening of mines in Australia and the USA and other mines are slow to follow. As a result, short supply of particularly terbium, dysprosium, praseodymium, and neodymium is expected to be problematic for at least the short term, also because they cannot be substituted. Recycling REEs from electronic waste would be a solution, but so far there are hardly any established REE recycling methods. Decreasing the dependency on REEs, for example, by identifying possible replacements or increasing their efficient use, represents another possibility. Urban mining of rare earth elements: Rare earth elements (REEs) are important resources for green and high-tech technologies. Export quotas, a price increase by a factor of ten, and geopolitical and sustainability concerns lead to the reopening of mines. The increased demand and decreased export will lead to a misbalance of four REEs (Nd, Tb, Dy, Pr) on the short term; therefore, as no alternatives are available yet, it is necessary to recycle these elements from electronic waste. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Objective To evaluate the performance of a directed non-invasive prenatal testing method of cell-free DNA analysis for fetal trisomy 21 (T21) by shipping the whole blood samples from Europe to a laboratory in the USA. Methods A European multicenter prospective, consecutive cohort study was performed enrolling pregnant women from Sweden and the Netherlands. Blood samples were drawn just prior to a planned of invasive diagnostic procedure in a population at increased risk for fetal T21 and then shipped to the USA without any blood processing. Chromosome-selective sequencing was carried out on chromosome 21 with reporting high risk or low risk of T21. Karyotyping or rapid aneuploidy detection was used as the clinical reference standard. Results Of the 520 eligible study subjects, a T21 test result was obtained in 504/520 (96.9%). Risk assessment was accurate in 503/504 subjects (99.8%). There was one false negative result for T21 (sensitivity 17/18, 94.4%, and specificity 100%). Conclusion This is the first prospective European multicenter study showing that non-invasive prenatal testing using directed sequencing of cell-free DNA applied to blood samples shipped across the Atlantic Ocean, is highly accurate for assessing risk of fetal T21. © 2013 John Wiley & Sons, Ltd.

Objective The mechanisms underlying obesity-related hypertension are incompletely understood. Microvascular dysfunction might play a role by increasing peripheral vascular resistance (PVR). Metabolic and microvascular effects of insulin are impaired in obesity, but how these impairments contribute to disturbed blood pressure homeostasis is unclear. Specifically, it is unknown whether local microvascular vasoactive effects of insulin play a role in determining systemic vascular resistance. The aim of this study was to investigate the association between PVR and local microvascular effects of insulin. Design and Methods Thirty-seven healthy, overweight subjects (age 25-55 years, BMI 25-30 kg/m2) were cross-sectionally studied. Local insulin-mediated vasodilation was measured using skin laser Doppler fluxmetry combined with transcutaneous iontophoresis of insulin. For comparison, local vasodilatory effects of acetylcholine and sodium nitroprusside were measured. PVR was calculated from mean arterial pressure and cardiac output, assessed by pulse-dye densitometry. Results PVR was inversely correlated with insulin-mediated vasodilation (r = −0.50; P < 0.01). This finding was maintained after adjustment for age, sex, blood pressure, and smoking. PVR was not associated with local microvascular effects of acetylcholine. Conclusions Our study in overweight subjects suggests that insulin's role in the microvasculature may contribute to blood pressure control.

Transfusion-related immunomodulation (TRIM) encompasses immunosuppressive and proinflammatory effects induced by red blood cell (RBC) transfusion. Changes that occur during storage in the RBC product have been hypothesized to underlie TRIM, mediated by tolerance of toll-like receptors (TLR). We investigated whether transfusion of 35-day-stored autologous RBCs alters cytokine production in response to stimulation with lipopolysaccharide (LPS) or lipotheic acid (LTA), in a clinically relevant model of endotoxemia.Eighteen volunteers received 2 ng/kg LPS intravenously, followed by normal saline or 2- or 35-day-stored autologous RBC transfusion. Before LPS, before transfusion, and 6 hours after transfusion blood was collected to measure cytokine gene expression. Whole blood was used for ex vivo stimulation with LPS and LTA, after which cytokine levels were measured with enzyme-linked immunosorbent assay.In vivo LPS induced a biphasic response in cytokine mRNA with peak values 2 hours after LPS infusion. Storage time of RBC transfusion did not influence cytokine mRNA levels. In vivo infusion of LPS resulted in tolerance for ex vivo stimulation with LPS and LTA. However, transfusion of either fresh or stored RBCs did not further affect the capacity to produce cytokines after ex vivo stimulation.In a clinically relevant model of human endotoxemia, autologous transfusion of 35-day-stored RBCs does not influence cytokine mRNA levels nor does it change the capacity of white blood cells in whole blood to produce cytokines after ex vivo stimulation with LPS or LTA.

Extensive surgical procedures to achieve maximal cytoreduction in patients with advanced stage epithelial ovarian cancer (EOC) are inevitably associated with postoperative morbidity and mortality. This study aimed to identify preoperative predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC and to develop a nomogram for individual risk assessment.Patients in The Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007. All peri- and postoperative complications within 30 days after surgery were registered and classified. To investigate predictors of 30-day morbidity, a Cox proportional hazard model with backward stepwise elimination was utilized. The identified predictors were entered into a nomogram. The main outcome was to identify parameters that predict operative risk.293 patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. Thirty-day morbidity was seen in 99 (34%) patients. Morbidity could be predicted by age (p = 0.033; OR 1.024), preoperative hemoglobin (p = 0.194; OR 0.843), and WHO performance status (p = 0.015; OR 1.821) with a optimism-corrected c-statistic of 0.62. Determinants co-morbidity status, serum CA125 level, platelet count, and presence of ascites were comparable in both groups.Thirty-day morbidity after primary cytoreductive surgery for advanced stage EOC could be predicted by age, hemoglobin, and WHO performance status. The generated nomogram could be valuable for predicting operative risk in the individual patient.

Objective Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. Preclinical studies have shown that aged RBCs can induce transfusion-related acute lung injury in the presence of a "first hit" (e.g., sepsis). Clinical studies, however, show conflicting results on this matter. We tested whether maximally stored RBCs are able to induce lung injury in the presence of a "first hit" in humans (Dutch Trial Register: NTR4455). Design Open-label, randomized controlled trial. Patients Healthy male volunteers. Interventions Eighteen healthy male volunteers donated one unit of autologous RBCs 2 or 35 days before the experiment. The experiment was started by infusion of 2 ng/kg lipopolysaccharide ("first hit"). After 2 hours, volunteers received normal saline (n = 6), 2-day stored transfusion (n = 6), or 35-day stored transfusion (n = 6) ("second hit"). Blood was sampled hourly. Six hours after transfusion, the diffusion capacity of the lungs for carbon monoxide was tested and volunteers underwent spirometry, chest x-ray study, and a bronchoalveolar lavage. Measurements and main results All volunteers fulfilled sepsis criteria after lipopolysaccharide injection. The stored blood transfusion did not result in significant changes in either hemodynamic or respiratory variables compared with the control groups. Furthermore, chest x-rays, lung function, and PaO2/FIO2 ratios did not differ between groups. Transfusion of stored autologous RBCs did not result in an increased level of protein in the lungs or neutrophil influx. Conclusions Transfusion of 35-day stored autologous RBCs in the presence of endotoxemia does not result in lung injury in humans.

a b s t r a c t Background: Studies have shown that self-sampling for hrHPV testing (HPV self-sampling) is highly acceptable to women, increases screening participation rate, and may therefore further reduce cervi- cal cancer incidence. However, it is important to clinically validate HPV self-sampling procedures for screening purposes. Objectives: Clinical validation of combined brush-based self-sampling with GP5+/6+-PCR EIA for primary cervical screening. In addition, HPV type-specific agreement between sample types and acceptability of brush-based self-sampling were evaluated. Study design: 135 women referred for colposcopy took a self-sample at home prior to vaginal- and cervical sampling by a gynaecologist. All women were biopsied for histology. HPV testing was done by GP5+/6+- PCR EIA, with genotyping by reverse line blotting (RLB). Acceptability of sampling methods was measured with a questionnaire. Results: In this outpatient population, hrHPV test results showed good concordance between self-samples and physician-taken cervical scrapes (86%, k = 0.70), with sensitivities and specificities for CIN2+ that did not differ significantly (93% and 51%, 91% and 51%, respectively (P = 1.0)). The clinical sensitivity of brush-based self-sampling combined with GP5+/6+-PCR EIA hrHPV testing for detection of CIN2+ was non-inferior to that of hrHPV testing on physician-taken cervical samples (P = 0.018). In addition, hrHPV genotyping results were highly concordant between sample types, with almost perfect agreement for HPV16 (k = 0.81) and HPV18 (k = 0.92). Finally, 91% of participants described brush-based self-sampling as easy-to-use. Conclusions: Brush-based self-sampling in combination with GP5+/6+-PCR EIA hrHPV testing is acceptable to women and valid for assessing the risk of CIN2+ in comparison to hrHPV testing on physician-taken scrapes. In addition, there was high concordance of HPV genotyping results. Therefore, this HPV self

Designing reliable MEMS structures presents numerous challenges. Polycrystalline silicon fractures in a brittle manner with considerable variability in measured strength. Furthermore, it is not clear how to use measured tensile strength data to predict the strength of a complex MEMS structure. To address such issues, two recently developed high-throughput MEMS tensile test techniques have been used to estimate strength distribution tails by testing approximately 1500 tensile bars. There is strong evidence that the micromachined polycrystalline silicon that was tested in this paper has a lower bound to its tensile strength (i.e., a strength threshold). Process-induced sidewall flaws appear to be the main source of the variability in tensile strength. Variations in as-fabricated dimensions, stress inhomogeneity within a polycrystal, and variations in the apparent fracture toughness do not appear to be dominant contributors to tensile strength variability. The existence of a strength threshold implies that there is maximum flaw size, which consequently enables a linear elastic fracture mechanics flaw-tolerance analysis. This approach was used to estimate a lower bound for the strength of a double edge-notched specimen that compared favorably with our measured values.

Accurate measurement of material strength at small scales is of critical importance for the design and manufacture of reliable micro- and nanoscale devices. Many materials of interest, e.g., polycrystalline silicon (polysilicon) and silicon carbide, are brittle, with statistical strength distributions. Therefore, strength quantification requires a large number of tests accurately performed on a practical platform. Here, analysis and testing of a compact on-chip microtensile test system, recently presented in a brief communication [Hazra et al., Journal of Micromechanics & Microengineering, 2009], is expanded significantly. We present new data on strength, alignment precision, temperature distribution, compliance calibration, stiffness ratio, force calibration, and effect of monolayer film coverage. High force (up to 30 mN) is applied to a 70-μm-long freestanding tensile bar (nominally of 2 μm width and 2.25 μm height) by cooling a thermal actuator (TA) that has gripped a crosshead via a prehensile mechanism. According to finite element analysis, specimen heating is small (

A 35-year-old primigravida, pregnant after in-vitro fertilization, was seen because of a trisomy 13/trisomy 18 (T13/T18) risk of 1:55, based on the result of her first-trimester combined test. She elected for non-invasive prenatal testing (NIPT) at 14 + 5 weeks' gestation, which was positive for T13. After counseling, the patient elected to undergo amniocentesis. Quantitative fluorescence polymerase chain reaction (QF-PCR) showed no signs of trisomy, and full karyotyping confirmed a normal 46,XY result. Analysis of the published literature on NIPT for T13 gives an overall detection rate of 91.6%, with a false-positive rate of 0.097%. Based on this detection rate, hypothetical calculations show that the positive predictive value is highly dependent on the prevalence of the disease, resulting in an unfavorable balance between benefit and harm in a general population.