Considering multifetal pregnancy reduction in triplet pregnancies: do we forget the emotional impact on fathers? A qualitative study from The Netherlands.

STUDY QUESTION: What factors influence the decision-making process of fathers regarding multifetal pregnancy reduction or maintaining a triplet pregnancy, and how do these decisions impact their psychological well-being? SUMMARY ANSWER: For fathers, the emotional impact of multifetal pregnancy reduction or caring for triplets is extensive and requires careful consideration. WHAT IS KNOWN ALREADY: Multifetal pregnancy reduction is a medical procedure with the purpose to reduce the number of fetuses to improve chances of a healthy outcome for both the remaining fetus(es) and the mother, either for medical reasons or social considerations. Aspects of the decision whether to perform multifetal pregnancy reduction have been rarely investigated, and the impact on fathers is unknown. STUDY DESIGN, SIZE, DURATION: Qualitative study with semi-structured interviews between October 2021 and February 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fathers either after multifetal pregnancy reduction from triplet to twin or singleton pregnancy or ongoing triplet pregnancies 1-6 years after the decision were included. The interview schedule was designed to explore key aspects related to (i) the decision-making process whether to perform multifetal pregnancy reduction and (ii) the emotional aspects and psychological impact of the decision. Thematic analysis was used to identify patterns and trends in the father's data. The process involved familiarization with the data, defining and naming themes, and producing a final report. This study was a collaboration between a regional secondary hospital (OLVG) and a tertiary care hospital (Amsterdam University Medical Center, Amsterdam UMC), both situated in Amsterdam, The Netherlands. MAIN RESULTS AND THE ROLE OF CHANCE: Data saturation was achieved after 12 interviews. Five main themes were identified: (i) initial responses and emotional complexity, (ii) experiencing disparities in counselling quality and post-decision care, (iii) personal influences on the decision journey, (iv) navigating parenthood: choices, challenges, and emotional adaptation, and (v) shared wisdom and lessons. For fathers, the decision whether to maintain or reduce a triplet pregnancy is complex, in which medical, psychological but mainly social factors play an important role. In terms of psychological consequences after the decision, this study found that fathers after multifetal pregnancy reduction often struggled with difficult emotions towards the decision; some expressed feelings of doubt or regret and were still processing these emotions. Several fathers after an ongoing triplet had experienced a period of severe stress in the first years after the pregnancy, with major consequences for their mental health. Help in emotional processing was not offered to any of the fathers after the decision or birth. LIMITATION, REASONS FOR CAUTION: While our study focuses on the multifetal pregnancy reduction process in the Amsterdam region, we recognize the importance of further investigation into how this process may vary across different regions in The Netherlands and internationally. We acknowledge the potential of selection bias, as fathers with more positive experiences might have been more willing to participate. Caution is needed in interpreting the role of the mother in the recruitment process. Additionally, the time span of 1-6 years between the decision and the interviews may have influenced emotional processing and introduced potential reporting bias. WIDER IMPLICATIONS OF THE FINDINGS: The emotional impact of multifetal pregnancy reduction or caring for triplets is significant, emphasizing the need for awareness among caregivers regarding the emotional challenges faced by fathers. A guided trajectory might optimize the decision-making and primarily facilitate the provision of appropriate care thereafter to optimize outcomes around decisions with potential traumatic implications. STUDY FUNDING/COMPETING INTEREST(S): This study received no funding. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Gene expression profiles in clinically T1-2N0 ER+HER2- breast cancer patients treated with breast-conserving therapy: their added value in case sentinel lymph node biopsy is not performed.

PURPOSE: Omitting sentinel lymph node biopsy (SLNB) in breast cancer treatment results in patients with unknown positive nodal status and potential risk for systemic undertreatment. This study aimed to investigate whether gene expression profiles (GEPs) can lower this risk in cT1-2N0 ER+ HER2- breast cancer patients treated with BCT. METHODS: Patients were included if diagnosed between 2011 and 2017 with cT1-2N0 ER+ HER2- breast cancer, treated with BCT and SLNB, and in whom GEP was applied. Adjuvant chemotherapy recommendations based on clinical risk status (Dutch breast cancer guideline of 2020 versus PREDICT v2.1) with and without knowledge on SLNB outcome were compared to GEP outcome. We examined missing adjuvant chemotherapy indications, and the number of GEPs needed to identify one patient at risk for systemic undertreatment. RESULTS: Of 3585 patients, 2863 (79.9%) had pN0 and 722 (20.1%) pN + disease. Chemotherapy was recommended in 1354 (37.8% guideline-2020) and 1888 patients (52.7% PREDICT). Eliminating SLNB outcome (n = 722) resulted in omission of chemotherapy recommendation in 475 (35.1% guideline-2020) and 412 patients (21.8% PREDICT). GEP revealed genomic high risk in 126 (26.5% guideline-2020) and 82 patients (19.9% PREDICT) in case of omitted chemotherapy recommendation in the absence of SLNB. Extrapolated to the whole group, this concerns 3.5% and 2.3%, respectively, resulting in the need for 28-44 GEPs to identify one patient at risk for systemic undertreatment. CONCLUSION: If no SLNB is performed, clinical risk status according to the guideline of 2020 and PREDICT predicts a very low risk for systemic undertreatment. The number of GEPs needed to identify one patient at risk for undertreatment does not justify its standard use.

Transient anti-cytokine autoantibodies superimpose the hyperinflammatory response in Kawasaki disease and multisystem inflammatory syndrome in children: a comparative cohort study on correlates of disease.

BACKGROUND: Children with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C) often present with clinical features that resemble Kawasaki disease (KD). Disease severity in adult COVID-19 is associated to the presence of anti-cytokine autoantibodies (ACAAs) against type I interferons. Similarly, ACAAs may be implicated in KD and MIS-C. Therefore, we explored the immunological response, presence of ACAAs and disease correlates in both disorders. METHODS: Eighteen inflammatory plasma protein levels and seven ACAAs were measured in KD (n = 216) and MIS-C (n = 56) longitudinally by Luminex and/or ELISA. Levels (up to 1 year post-onset) of these proteins were related to clinical data and compared with healthy paediatric controls. FINDINGS: ACAAs were found in both patient groups. The presence of ACAAs lagged behind the inflammatory plasma proteins and peaked in the subacute phase. ACAAs were mostly directed against IFN-γ (>80%) and were partially neutralising at best. KD presented with a higher variety of ACAAs than MIS-C. Increased levels of anti-IL-17A (P = 0·02) and anti-IL-22 (P = 0·01) were inversely associated with ICU admission in MIS-C. Except for CXCL10 in MIS-C (P = 0·002), inflammatory plasma proteins were elevated in both KD and MIS-C. Endothelial angiopoietin-2 levels were associated with coronary artery aneurysms in KD (P = 0·02); and sCD25 (P = 0·009), angiopoietin-2 (P = 0·001), soluble IL-33-receptor (ST2, P = 0·01) and CXCL10 (P = 0·02) with ICU admission in MIS-C. INTERPRETATION: Markers of endothelial activation (E-selectin, angiopoietin-2), and innate and adaptive immune responses (macrophages [CD163, G-CSF], neutrophils [lipocalin-2], and T cells [IFN-γ, CXCL10, IL-6, IL-17]), are upregulated in KD and MIS-C. ACAAs were detected in both diseases and, although only partly neutralising, their transient presence and increased levels in non-ICU patients may suggest a dampening role on inflammation. FUNDING: The Kawasaki study is funded by the Dutch foundation Fonds Kind & Handicap and an anonymous donor. The sponsors had no role in the study design, analysis, or decision for publication.

Identification of a methylation panel as an alternative triage to detect CIN3+ in hrHPV-positive self-samples from the population-based cervical cancer screening programme.

BACKGROUND: The Dutch population-based cervical cancer screening programme (PBS) consists of primary high-risk human papilloma virus (hrHPV) testing with cytology as triage test. In addition to cervical scraping by a general practitioner (GP), women are offered self-sampling to increase participation. Because cytological examination on self-sampled material is not feasible, collection of cervical samples from hrHPV-positive women by a GP is required. This study aims to design a methylation marker panel to detect CIN3 or worse (CIN3+) in hrHPV-positive self-samples from the Dutch PBS as an alternative triage test for cytology. METHODS: Fifteen individual host DNA methylation markers with high sensitivity and specificity for CIN3+ were selected from literature and analysed using quantitative methylation-specific PCR (QMSP) on DNA from hrHPV-positive self-samples from 208 women with CIN2 or less (< CIN2) and 96 women with CIN3+. Diagnostic performance was determined by area under the curve (AUC) of receiver operating characteristic (ROC) analysis. Self-samples were divided into a train and test set. Hierarchical clustering analysis to identify input methylation markers, followed by model-based recursive partitioning and robustness analysis to construct a predictive model, was applied to design the best marker panel. RESULTS: QMSP analysis of the 15 individual methylation markers showed discriminative DNA methylation levels between < CIN2 and CIN3+ for all markers (p < 0.05). The diagnostic performance analysis for CIN3+ showed an AUC of ≥ 0.7 (p < 0.001) for nine markers. Hierarchical clustering analysis resulted in seven clusters with methylation markers with similar methylation patterns (Spearman correlation> 0.5). Decision tree modeling revealed the best and most robust panel to contain ANKRD18CP, LHX8 and EPB41L3 with an AUC of 0.83 in the training set and 0.84 in the test set. Sensitivity to detect CIN3+ was 82% in the training set and 84% in the test set, with a specificity of 74% and 71%, respectively. Furthermore, all cancer cases (n = 5) were identified. CONCLUSION: The combination of ANKRD18CP, LHX8 and EPB41L3 revealed good diagnostic performance in real-life self-sampled material. This panel shows clinical applicability to replace cytology in women using self-sampling in the Dutch PBS programme and avoids the extra GP visit after a hrHPV-positive self-sampling test.

National-Level Schoolwork Pressure, Family Structure, Internet Use, and Obesity as Drivers of Time Trends in Adolescent Psychological Complaints Between 2002 and 2018.

Little is known about societal processes that contribute to changes in adolescent mental health problems. This study aims to fill this gap using data from the Health Behavior in School-aged Children study between 2002 and 2018 (ncountries = 43, nindividuals = 680,269, Mage = 14.52 (SD = 1.06), 51.04% female), supplemented with other international data. National-level psychological complaints increased more strongly among girls than boys. National-level schoolwork pressure, single-parent households, time spent on internet, and obesity were generally rising. In both boys' and girls' samples, increases in national-level schoolwork pressure, obesity, and time spent on internet use were independently associated with increases national-level psychological complaints. However, national-level obesity and psychological complaints were more strongly related among girls than boys. Results highlight the potential impact of societal-level processes on adolescent mental health problems.

Contesting misrecognition online: Experiences of epistemic in/justice by vloggers with contested illnesses.

Contested illnesses, such as fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and chronic Lyme disease (CLD), are surrounded by polemic debates regarding their etiology, symptomology, treatment, and even their existence. People who suffer from these contested illnesses arguably also suffer from "epistemic injustice." This concept, coined by the philosopher Miranda Fricker, captures how people's knowledge may be discredited because of identity prejudices. In our paper, this concept is used to understand how seven Dutch women with contested illnesses experience the emancipatory potential of their vlogging practices. Our findings show how these women understood their vlogging as a means to break with epistemic smothering, understood as the propensity to cater ones testimony to one's audience (Dotson, 2011), and as a means to attain and enhance epistemic justice. However, our findings also show how vlogging about contested illnesses did not seem to allow these women to fully break with their epistemic smothering practices, and that the ableist design and gendered norms of YouTube were experienced as obstacles to attaining epistemic justice. We conclude that, even though social media do seem to hold emancipatory potential for these women, the experiences of individual users are diverse and ambiguous.

Determining the gluonic gravitational form factors of the proton.

The proton is one of the main building blocks of all visible matter in the Universe1. Among its intrinsic properties are its electric charge, mass and spin2. These properties emerge from the complex dynamics of its fundamental constituents-quarks and gluons-described by the theory of quantum chromodynamics3-5. The electric charge and spin of protons, which are shared among the quarks, have been investigated previously using electron scattering2. An example is the highly precise measurement of the electric charge radius of the proton6. By contrast, little is known about the inner mass density of the proton, which is dominated by the energy carried by gluons. Gluons are hard to access using electron scattering because they do not carry an electromagnetic charge. Here we investigated the gravitational density of gluons using a small colour dipole, through the threshold photoproduction of the J/ψ particle. We determined the gluonic gravitational form factors of the proton7,8 from our measurement. We used a variety of models9-11 and determined, in all cases, a mass radius that is notably smaller than the electric charge radius. In some, but not all cases, depending on the model, the determined radius agrees well with first-principle predictions from lattice quantum chromodynamics12. This work paves the way for a deeper understanding of the salient role of gluons in providing gravitational mass to visible matter.

A new approach to drug intravenous compatibility research: the case of obstetric parenteral drugs.

OBJECTIVES: The product information and literature does not provide confirmation of compatibility for co-administration of all commonly used drug pairs in obstetrics. However, there is a need for co-administration of these drugs over one lumen for this group of patients. Therefore, this study focuses on Y-site compatibility. Since different conditions between clinical and laboratory settings can lead to discrepancies in results, a novel approach for drug intravenous compatibility testing was designed to reflect clinical conditions. The aim was to study the compatibility of nine commonly used drug pairs in obstetrics and to evaluate the clinical value of the designed method. METHODS: The clinical situation was reflected by using different temperature ranges (20°C and 37°C), actual Y-site flow ratios, clinically relevant drug pairs and an observation time of 120 min. The clinically relevant drugs pairs include atosiban, nicardipine, amoxicillin/clavulanic acid, oxytocin, remifentanil, labetalol and magnesium sulpfate. Drug pairs were visually assessed according to the European Pharmacopoeia (Ph. Eur.) and pH was measured. When incompatibility of a drug pair seemed likely based on literature review or observed abnormalities during visual assessment, subvisual analysis was performed using a particle counter. Y-site compatibility applied for drug pairs when no visual changes occurred or when no additional particles were formed during the observation time. RESULTS: Eight of the nine combinations showed no visual changes or noticeable changes in pH during the observation time. The amoxicillin/clavulanic-acid-oxytocin combination showed a colour change at 37°C at the actual Y-site flow ratio. However, subvisual particle counting showed no formation of additional particles. CONCLUSIONS: Y-site compatibility was established for all tested drug pairs. The new clinical approach for analysing Y-site compatibility provides a high certainty of outcomes for clinical practice. In this way, clinical complications and use of several additional intravenous catheters can be avoided.

Stimulus contrast, pursuit mode, and age strongly influence tracking performance on a continuous visual tracking task.

Human observers tend to naturally track moving stimuli. This tendency may be exploited towards an intuitive means of screening visual function as an impairment induced reduction in stimulus visibility will decrease tracking performance. Yet, to be able to detect subtle impairments, stimulus contrast is critical. If too high, the decrease in performance may remain undetected. Therefore, for this approach to become reliable and sensitive, we need a detailed understanding of how age, stimulus contrast, and the type of stimulus movement affect continuous tracking performance. To do so, we evaluated how well twenty younger and twenty older participants tracked a semi-randomly moving stimulus (Goldmann size III, 0.43 degrees of visual angle), presented at five contrast levels (5%-10%-20%-40%-80%). The stimulus could move smoothly only (smooth pursuit mode) or in alternation with displacements (saccadic pursuit mode). Additionally, we assessed static foveal and peripheral contrast thresholds. For all participants, tracking performance improved with increasing contrast in both pursuit modes. To reach threshold performance levels, older participants required about twice as much contrast (20% vs. 10% and 40% vs. 20% in smooth and saccadic modes respectively). Saccadic pursuit detection thresholds correlated significantly with static peripheral contrast thresholds (rho = 0.64). Smooth pursuit detection thresholds were uncorrelated with static foveal contrast thresholds (rho = 0.29). We conclude that continuous visual stimulus tracking is strongly affected by stimulus contrast, pursuit mode, and age. This provides essential insights that can be applied towards new and intuitive approaches of screening visual function.

AbcApp: incidence of intra-abdominal ABsCesses following laparoscopic vs. open APPendectomy in complicated appendicitis.

BACKGROUND: Patients with complicated appendicitis are more at risk for the occurrence of postoperative intra-abdominal abscesses than patients with uncomplicated appendicitis. Studies comparing laparoscopic and open appendectomy showed limitations and contradictory findings on the incidence of intra-abdominal abscesses after appendicitis, as most of these studies analysed both uncomplicated and complicated appendicitis as one group. The aim of the present study is to investigate the incidence of intra-abdominal abscesses after laparoscopic versus open appendectomy for complicated appendicitis. METHODS: A retrospective cohort study was performed over the period January 2009 till May 2020. All patients who had an intra-operative diagnosis of complicated appendicitis (e.g. perforation, necrosis) were included. The outcome measure was the occurrence of intra-abdominal abscesses with a postoperative follow-up of 30 days. Multivariate logistic regression analysis was performed including adjustments for significant confounders. RESULTS: A total of 900 patients had undergone appendectomy for complicated appendicitis. The majority was operated laparoscopically (78%, n = 705). The incidence of postoperative intra-abdominal abscess was 12.3% in both laparoscopic and open appendectomy groups. On univariable analysis, the postoperative rates of intra-abdominal abscesses between laparoscopic and open appendectomy were not significantly different (odds ratio 1.11, 95% CI [0.67-1.84], p = 0.681). CONCLUSION: The present study provides evidence that, in current daily practice, intra-abdominal abscess formation remains a common postoperative complication for complicated appendicitis. Nonetheless, no significant difference was found with regard to intra-abdominal abscess formation when comparing laparoscopy with open surgery.

Inflammatory responses in SARS-CoV-2 associated Multisystem Inflammatory Syndrome and Kawasaki Disease in children: An observational study.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a severe inflammatory disease in children related to SARS-CoV-2 with multisystem involvement including marked cardiac dysfunction and clinical symptoms that can resemble Kawasaki Disease (KD). We hypothesized that MIS-C and KD might have commonalities as well as unique inflammatory responses and studied these responses in both diseases. In total, fourteen children with MIS-C (n=8) and KD (n=6) were included in the period of March-June 2020. Clinical and routine blood parameters, cardiac follow-up, SARS-CoV-2-specific antibodies and CD4+ T-cell responses, and cytokine-profiles were determined in both groups. In contrast to KD patients, all MIS-C patients had positive Spike protein-specific CD3+CD4+ T-cell responses. MIS-C and KD patients displayed marked hyper-inflammation with high expression of serum cytokines, including the drug-targetable interleukin (IL)-6 and IFN-γ associated chemokines CXCL9, 10 and 11, which decreased at follow-up. No statistical differences were observed between groups. Clinical outcomes were all favourable without cardiac sequelae at 6 months follow-up. In conclusion, MIS-C and KD-patients both displayed cytokine-associated hyper-inflammation with several high levels of drug-targetable cytokines.

Co-occurrence of pectenotoxins and Dinophysis miles in an Indonesian semi-enclosed bay.

The study aims to unravel the variability of Dinophysis spp. and their alleged toxins in conjunction with environmental drivers in Ambon Bay. Phytoplankton samples, lipophilic toxins and physiochemical water properties were analysed during a 1.5-year period. Three Dinophysis species (D. miles, D. caudata, and D. acuminata) were found in plankton samples, of which D. miles was the most abundant and persistently occurring species. Pectenotoxin-2 (PTX2) and its secoacid (PTX2sa) were detected throughout, and PTX2sa levels strongly correlated with D. miles cell abundance. The toxin showed a positive correlation with temperature, which may suggest that D. miles cells contain rather constant PTX2sa during warmer months. Dissolved nitrate concentrations were found to play a major role in regulating cell abundances and toxin levels. This study adds adequate information regarding marine biotoxins and potentially toxic species for future Harmful Algal Bloom management in Ambon and Indonesia at large.

Measured proton electromagnetic structure deviates from theoretical predictions.

The visible world is founded on the proton, the only composite building block of matter that is stable in nature. Consequently, understanding the formation of matter relies on explaining the dynamics and the properties of the proton's bound state. A fundamental property of the proton involves the response of the system to an external electromagnetic field. It is characterized by the electromagnetic polarizabilities1 that describe how easily the charge and magnetization distributions inside the system are distorted by the electromagnetic field. Moreover, the generalized polarizabilities2 map out the resulting deformation of the densities in a proton subject to an electromagnetic field. They disclose essential information about the underlying system dynamics and provide a key for decoding the proton structure in terms of the theory of the strong interaction that binds its elementary quark and gluon constituents. Of particular interest is a puzzle in the electric generalized polarizability of the proton that remains unresolved for two decades2. Here we report measurements of the proton's electromagnetic generalized polarizabilities at low four-momentum transfer squared. We show evidence of an anomaly to the behaviour of the proton's electric generalized polarizability that contradicts the predictions of nuclear theory and derive its signature in the spatial distribution of the induced polarization in the proton. The reported measurements suggest the presence of a new, not-yet-understood dynamical mechanism in the proton and present notable challenges to the nuclear theory.

Bone defect development in experimental canine peri-implantitis models: a systematic review.

PURPOSE: To provide a systematic overview of preclinical research regarding bone defect formation around different implant surfaces after ligature-induced peri-implantitis models in dogs. Two focused questions were formulated: 'How much bone loss can be expected after a certain time of ligature induced peri-implantitis?' and 'Do different implant types, dog breeds and study protocols differ in their extent of bone loss?' MATERIALS AND METHODS: A systematic literature search was conducted on four databases (MEDLINE, Web of Science, EMBASE and Scopus). Observations, which consisted of bone defects measured directly after ligature removal in canine models, were included and analysed. Two approaches were used to analyse the relatively heterogeneous studies that fulfilled the inclusion criteria. First, separate simple linear regressions were calculated for each study and implant surface, for which observations were available across multiple time points. Second, a linear mixed model was specified for the observations at 12 weeks after ligature initiation, and assessing the potential influencing factors on defect depth was explored using lasso regularisation. RESULTS: Thirty-six studies with a total of 1082 implants were included after. Bone loss was determined at different time points, either with clinical measurements radiographically or histologically. Different implant groups [e.g. turned, sand-blasted-acid-etched (SLA), titanium-plasma-sprayed (TPS) and other rough surfaces] were assessed and described in the studies. A mean incremental defect depth increase of 0.08 mm (SD: -0.01-0.28 mm) per week was observed. After 12 weeks, the defect depths ranged between 0.7 and 5 mm. Based on the current data set, implant surface could not be statistically identified as an essential factor in defect depth after 12 weeks of ligature-induced peri-implantitis. CONCLUSION: Expectable defect depth after a specific time of ligature-induced peri-implantitis can vary robustly. It is currently impossible to delineate apparent differences in bone loss around different implant surfaces.

Final benefit of primary percutaneous coronary intervention for ST-elevation myocardial infarction in older patients: long-term results of a randomised trial.

BACKGROUND: Although the short-term benefit of primary percutaneous coronary intervention (PCI) in elderly patients with ST-elevation myocardial infarction (STEMI) has been demonstrated, the final long-term survival benefit is as yet unknown. AIM: To assess the final survival benefit of primary PCI as compared to thrombolytic therapy in patients over 75 years of age. METHODS: Patients > 75 years with STEMI were randomised to either primary PCI or thrombolysis. Long-term data on survival were available for all patients. RESULTS: A total of 46 patients were randomised to primary PCI, 41 to thrombolysis. There were no significant differences in baseline variables. After a maximum of 20 years' follow-up, all patients had passed away. The patients randomised to thrombolysis died after a mean follow-up duration of 5.2 years (SD 4.9) compared to 6.7 years (SD 4.8) in patients randomised to primary PCI (p = 0.15). Thus, the mean final survival benefit of primary PCI was 1.5 years. CONCLUSION: The final survival benefit of primary PCI as compared to thrombolysis in elderly patients with STEMI is 1.5 years and their life expectancy increases by 28.8%.

Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy.

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

Current clinical practice in antibiotic treatment of Staphylococcus aureus bacteraemia: results from a survey in five European countries.

OBJECTIVES: To determine clinical practice variation and identify knowledge gaps in antibiotic treatment of Staphylococcus aureus bacteraemia (SAB). METHODS: A web-based survey with questions addressing antibiotic treatment of SAB was distributed through the ESGAP network among infectious disease specialists, clinical microbiologists and internists in Croatia, France, Greece, the Netherlands and the UK between July 2021 and November 2021. RESULTS: A total number of 1687 respondents opened the survey link, of whom 677 (40%) answered at least one question. For MSSA and MRSA bacteraemia, 98% and 94% preferred initial monotherapy, respectively. In patients with SAB and non-removable infected prosthetic material, between 80% and 90% would use rifampicin as part of the treatment. For bone and joint infections, 65%-77% of respondents would consider oral step-down therapy, but for endovascular infections only 12%-32% would. Respondents recommended widely varying treatment durations for SAB with different foci of infection. Overall, 48% stated they used 18F-fluorodeoxyglucose positron emission tomography/CT (18F-FDG-PET/CT) to guide antibiotic treatment duration. Persistent bacteraemia was the only risk factor for complicated SAB that would prompt a majority to extend treatment from 2 to 4-6 weeks. CONCLUSIONS: This survey in five European countries shows considerable clinical practice variation between and within countries in the antibiotic management of SAB, in particular regarding oral step-down therapy, choice of oral antibiotic agents, treatment duration and use of 18F-FDG-PET/CT. Physicians use varying criteria for treatment decisions, as evidence from clinical trials is often lacking. These areas of practice variation could be used to prioritize future studies for further improvement of SAB care.

Value of routine intraoperative frozen sections of proximal bile duct margins in perihilar cholangiocarcinoma, a retrospective multicenter and matched case-control study.

BACKGROUND: Currently, the potential benefits of additional resection after positive proximal intraoperative frozen sections (IFS) in perihilar cholangiocarcinoma (pCCA) on residual disease and oncological outcome remain uncertain. Therefore, the aim of this study is to investigate the number of R0 resections after additional resection of a positive proximal IFS and the influence of additional resections on overall survival (OS) in patients with pCCA. MATERIALS AND METHODS: A retrospective, multicenter, matched case-control study was performed, including patients undergoing resection for pCCA between 2000 and 2019 at three tertiary centers. Primary outcome was the number of achieved 'additional' R0 resections. Secondary outcomes were OS, recurrence, severe morbidity and mortality. RESULTS: Forty-four out of 328 patients undergoing resection for pCCA had a positive proximal IFS. An additional resection was performed in 35 out of 44 (79.5%) patients, which was negative in 24 (68.6%) patients. Nevertheless, seven out of these 24 patients were eventually classified as R1 resection due to other positive resection margins. Therefore, 17 (48.6%) patients could be classified as "true" R0 resection after additional resection. Ninety-day mortality after R1 resections was high (25%) and strongly influenced OS. After correction for 90-day mortality, median OS after negative additional resection was 33 months (95%CI:29.5-36.5) compared to 30 months (95%CI:24.4-35.6) after initial R1 (P = 0.875) and 46 months (95%CI:32.7-59.3) after initial R0 (P = 0.348). CONCLUSION: There were only 17 patients (out of a total of 328 patients) that potentially benefitted from routine IFS. Additional resection for a positive IFS leading to R0 resection was not associated with improved long-term survival.

Impact of COVID-19 pandemic on diagnostic pathology in the Netherlands.

BACKGROUND: The COVID-19 pandemic has a huge impact on healthcare provided. The nationwide pathology registry of the Netherlands, PALGA, offers an outstanding opportunity to measure this impact for diseases in which pathology examinations are involved. METHODS: Pathology specimen numbers in 2020 were compared with specimen numbers in 2019 for 5 periods of 4 weeks, representing two lockdowns and the periods in between, taking into account localization, procedure and benign versus malignant diagnosis. RESULTS: The largest decrease was seen during the first lockdown (spring 2020), when numbers of pathology reports declined up to 88% and almost all specimen types were affected. Afterwards each specimen type showed its own dynamics with a decrease during the second lockdown for some, while for others numbers remained relatively low during the whole year. Generally, for most tissue types resections, cytology and malignant diagnoses showed less decrease than biopsies and benign diagnoses. A significant but small catch-up (up to 17%) was seen for benign cervical cytology, benign resections of the lower gastro-intestinal tract, malignant skin resections and gallbladder resections. CONCLUSION: The COVID-19 pandemic has had a significant effect on pathology diagnostics in 2020. This effect was most pronounced during the first lockdown, diverse for different anatomical sites and for cytology compared with histology. The data presented here can help to assess the consequences on (public) health and provide a starting point in the discussion on how to make the best choices in times of scarce healthcare resources, considering the impact of both benign and malignant disease on quality of life.