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Purpose: We aimed to provide an extended analysis of the physiological handling of of the sodium burden induced by maintenance fluids. Materials and methods: We revisited two studies that demonstrated, in healthy volunteers and in surgical patients, that maintenance fluids with 154 mmol/L of sodium lead to a more positive fluid balance than a regimen containing 54 mmol/L. We report different unpublished data on the renal handling of the imposed sodium bur -dens with specific attention to the resulting fluid and sodium balances. Results: The kidneys adapt to the sodium-rich fluids not only by altering sodium excretion, but also by retaining extra free water by concentrating urine. Realigning urinary sodium excretion with an increased administration takes around one day in health and much longer in the clinical setting. This difference may be explained by the presence of hypovolemia-induced aldosterone secretion in the latter group. Non-osmotic storage of sodium limits an unrestrained fluid retention even when very high amounts of sodium are administered but fluid accu-mulation will inevitably be further prolonged. Conclusions: Sodium administration induced by sodium-rich maintenance fluids leads, especially in the clinical setting, to prolonged fluid retention when compared with a regimen that resembles a healthy dietary sodium in-take, even when kidney function is normal. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Background: Sperm DNA fragmentation has been proposed as a candidate test for the assessment of sperm function on the premise that damage to the sperm chromatin is associated with a detrimental reproductive outcome. The objective of our study was to investigate whether sperm DNA fragmentation testing has a prognostic value, and thus can play a pivotal role in selecting future patients for intra-uterine insemination (IUI) therapy. Methods: This was a prospective cohort study conducted in a University Hospital setting. SDF was measured through TUNEL assay on the fresh semen sample presented at diagnosis and at insemination in couples with idiopathic/mild male infertility undergoing natural cycle IUI treatment. The generalized estimating equation (GEE)-model and multivariable model were used to analyze the probability of live birth and clinical pregnancy, respectively. ROC analysis was carried out to determine an SDF cut-off. Results: There was an inverse relationship between SDF in the ejaculate of the diagnostic semen sample and CP (p = 0.02; OR 0.94 95% CI (0.90, 0.989)) as well as LB (p = 0.04; OR 0.95 95% CI (0.90, 0.9985)). No significant association was found between SDF after gradient and IUI outcome in the diagnostic sample nor between SDF (ejaculate/after gradient) in the IUI samples. The ROC analysis proposed a cutoff of 17.5% as the best compromise between sensitivity and specificity in the diagnostic SDF for live birth; however, the test diagnostics are low, with an AUC of 0.576. Conclusions: Overall, this study strengthens the hypothesis of an inverse relationship between SDF and CP/LB. Furthermore, SDF taken together with other clinical characteristics might provide more insight into male reproductive potential and predicting IUI outcome. Couples with SDF ≥ 17.5% in the diagnostic semen sample did not reach live birth. Further research is necessary to establish the diagnostic and prognostic potential of SDF as an add-on test.

BackgroundPatients with cancer, especially haematological cancer, are at increased risk for breakthrough COVID-19 infection. However, so far, a predictive biomarker that can assess compromised vaccine-induced anti-SARS-CoV-2 immunity in cancer patients has not been proposed.MethodsHere, we employed machine learning approaches to identify a biomarker signature based on blood cytokine and growth factors linked to vaccine response from 199 cancer patients receiving BNT162b2 vaccine.ResultsWe show that C-reactive protein (CRP; general marker of inflammation), interleukin (IL)-15 (a pro-inflammatory cytokine), IL-18 (interferon-gamma inducing factor), and placental growth factor (an angiogenic cytokine) can correctly classify patients with a diminished vaccine response assessed at day 49 with >80% accuracy. Amongst these, CRP showed the highest predictive value for poor response to vaccine administration. Importantly, this unique signature of vaccine response was present at different studied timepoints both before and after vaccination and was not majorly affected by different anti-cancer treatments.ConclusionWhile we propose a blood-based signature of cytokines and growth factors that can be employed in identifying cancer patients at continued risk of COVID-19, our data also importantly suggest that such a signature could reflect the inherent make-up of some cancer patients who are also refractive to immunotherapy.

Introduction Currently cancer-related cognitive impairment (CRCI) is mainly assessed by means of questionnaires, which is very laborious for the patients and the supervising physician. We evaluated a new online cognitive assessment tool, the MyCognition Quotient (MyCQ, Cambridge) in breast cancer survivors with CRCI, and compared the results with a psychometric test measuring cognitive complaints, depression, and anxiety. Materials and methods In this prospective study, 46 adult patients between 18 and 70 years old with a diagnosis of BC were studied, all complaining of disturbing cognitive impairment. They participated in a physical cognitive rehabilitation program. The patients had an online cognitive assessment (MyCQ Med by MyCognition) every 4 weeks on their home computer. In addition patients were assessed in the outpatient clinic by the principal investigator at baseline, after 3 and 6 months using the following validated neuro-psychological surveys: the Hospital Anxiety and Depression Scale (HADS), Beck Cognitive Insight Scale (BCIS), and Cognitive Failure Questionnaire (CFQ). MyCQ scores were correlated with the results of these surveys. Results Only weak correlations could be found between overall MyCQ or the MyCQ subtests with the psychometric tests (between - 0.43 and 0.458) at baseline and when combining data at time point 0, 3, and 6 months. Linear mixed models showed there was a significant association between Latency Choice Reaction Time and CFQ (continuous; p = 0.026). An AUC of 0.640 and a cut-off of 481.5 ms in Latency Choice Reaction Time were found to distinguish patients with CFQ below 44 to patients with CFQ above 44 (sensitivity 0.63 and specificity 0.73). In Latency Coding an AUC of 0.788 and a cut-off of 1316 ms were found to distinguish non-depressive patients from patients likely to present with depressive symptoms (sensitivity 0.75 and specificity 0.76). Conclusion MyCQ cannot replace the various psychometric tests. However, abnormal Latency in cognitive tests, Choice Reaction Time and Coding, seems promising to be used as a screening tool to detect specific aspects of abnormal cognitive functioning in patients with cognitive complaints and depressive symptoms.

Background: Coronavirus disease (COVID-19) is interfering heavily with the screening, diagnosis and treatment of cancer patients. Better knowledge of the seroprevalence and immune response after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in this population is important to manage them safely during the pandemic. Methods: 922 cancer patients, 100 non-cancer patients and 94 health care workers (HCW) attending the Multidisciplinary Oncology Unit of Antwerp University Hospital from 24th of March 2020 till 31st of May 2020, and the Oncology Unit of AZ Maria Middelares Hospital, Ghent, from 13th of April 2020 till 31st of May 2020 participated in the study. The Alinity (A; Abbott) and Liaison (D; DiaSorin) commercially available assays were used to measure SARS-CoV-2 IgG, while total SARS-CoV-2 Ig was measured by Elecsys (R; Roche). Results: In the overall study population IgG/total SARS-CoV-2 antibodies were found in respectively 32/998 (3.2%), 68/1020 (6.7%), 37/1010 (3.7%) and of individuals using the A, D or R test. Forty-six out of 618 (7.4%) persons had a positive SARS-CoV-2 polymerase chain reaction (RT-PCR) test. Seroprevalence in cancer patients (A:2.2%, D:6.2%, R:3.0%), did not significantly differ from that in non-cancer patients (A:1.1%, D:5.6%, R:0.0%), but was lower than the HCW (A:13%, D:12%, R:12%; respectively Fisher’s exact test p Z 0.00001, p Z 0.046, p Z 0.0004). A positive SARS-CoV-2 RT-PCR was found in 6.8% of the cancer patients, 2.3% of the non-cancer patients and 28.1% of the HCW (Fisher’s exact test p Z 0.0004). Correlation between absolute values of the different Ig tests was poor in the cancer population. Dichotomising a positive versus negative test result, the A and R test correlated well (kappa 0.82 p McNemar test Z 0.344), while A and D and R and D did not (respectively kappa 0.49 and 0.57; result significantly different p McNemar test Z 75%) and median absolute antibody levels (A: 7.0 versus 4.7; D 74.0 versus 26.6, R: 16.34 versus 7.32; all >P Mann Whitney U test Z 0.28) in cancer patients and HCW with a positive RT-PCR at least 7 days earlier did not show any differences. However, none (N Z 0/4) of the patients with hematological tumours had seroconversion and absolute antibody levels remained much lower compared to patients with solid tumours (R: 0.1 versus 37.6, p 0.003; D 4.1 versus 158, p 0.008) or HCW (all p < 0.0001). Conclusion: HCW were at high risk of being infected by SARS-CoV-2 during the first wave of the pandemic. Seroprevalence in cancer patients was low in the study period. Although Ig immune response in cancer patients with solid tumours does not differ from healthy volunteers, patients with hematological tumours have a very poor humoral immune response. This has to be taken into account in future vaccination programmes in this population. SARS-CoV-2 antibody tests have divergent results and seem to have little added value in the management of cancer patients.

Introduction: Acute kidney injury (AKI) is a frequent complication among patients in the intensive care unit (ICU). The limitations of serum Cr (sCr) in timely detecting AKI are well known. Beta-trace protein (BTP) is emerging as a novel endogenous glomerular filtration rate marker. The aim of this study was to explore the role of BTP as a marker of AKI. Methods: Patients admitted to the ICU undergoing surgery were included. BTP, sCr, Cystatin C (CysC), and neutrophil gelatinase-associated lipocalin (NGAL) were measured preoperatively, postoperatively (post-op), and at the first (D1) and second (D2) post-op day. AKI was defined as an increase of sCr to ≥1.5-fold from baseline within 2 days after surgery. Results: Of the 52 patients studied, 10 patients (19%) developed AKI. Patients with AKI were older (69.6 ± 10.7 vs. 58.1 ± 16.7 years, p = 0.043) and had a longer length of ICU stay (13 [IQR 6–49] vs. 6 [IQR 5–8] days, p = 0.032). Between the 2 groups, the evolution of BTP, sCr, CysC, and NGAL over time differed significantly, with overall higher values in the AKI group. ROC analysis for the detection of AKI within 2 days after surgery showed a great accuracy for BTP. The area under the curve (AUC) for BTP post-op; D1; and D2 was, respectively, 0.869 ± 0.049; 0.938 ± 0.035; and 0.943 ± 0.032. The discriminative power of a BTP measurement on D1 was superior in detecting AKI compared to NGAL (adjusted p value = 0.027). We could not detect a significant difference between the AUCs of other biomarkers (NGAL, sCr, and CysC). Conclusion: Serum BTP is a promising marker for diagnosing AKI in ICU patients undergoing surgery.

There is a growing body of literature that recognizes the importance of sperm DNA fragmentation as a candidate test for the assessment of sperm function and thus male reproductive potential. Research on the subject has mostly been focused on couples undergoing IVF/ICSI treatment whilst much uncertainty still exists about the relationship between sperm DNA fragmentation and IUI. This study systematically reviews the literature, aiming to define the value of sperm DNA fragmentation measurement in predicting clinical pregnancy outcome in couples undergoing intra-uterine insemination From inception until March 2018, the relevant databases were searched for studies investigating the relationship between sperm DNA fragmentation as measured by SCSA, TUNEL, SCD or Comet assay and pregnancy outcome after IUI. The Quality in Prognosis Studies (QUIPS) tool was utilized for quality assessment. This review is reported according to the 2009 PRISMA statement. The literature search resulted in 433 studies of which we finally retained nine studies for the qualitative analysis and four studies for the meta-analysis, accounting for 940 IUI cycles. In summary, the observed effect of low sperm DNA fragmentation on clinical pregnancy after IUI as analyzed with the random effects model reveals a relative risk of 3.15 (95% CI: 1.46-6.79; 12 = 13.1%) and pooled sensitivity and specificity of respectively 94% (95% CI: 0.88; 0.97) and 19% (95% CI: 0.14; 0.26). Taken together, the included studies show a limited capacity of sperm DNA fragmentation in discriminating between couples who will benefit from the test, namely in either predicting IUI outcome or in advising for or against IUI as first choice of treatment instead of advancing to more invasive medically assisted reproduction. This review has thrown up many questions in need of further investigation. As such, future studies might explore issues such as determining relevant cut-off values for prediction of spontaneous pregnancy and pregnancy after IUI as well as the assessment of the stability of the test over time and before and after density gradient centrifugation. (C) 2019 Elsevier B.V. All rights reserved.

To perform a large-scale interchangeability study comparing 3D controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) sampling perfection with application optimized contrast using different flip angle evolutions (SPACE) TSE with standard 2D TSE for knee MRI.In this prospective study, 250 patients underwent 3 T knee MRI, including a multicontrast 3D CAIPIRINHA SPACE TSE (9:26 min) and a standard 2D TSE protocol (12:14 min). Thirty-three (13%) patients had previous anterior cruciate ligament and/or meniscus surgery. Two radiologists assessed MRIs for image quality and identified pathologies of menisci, ligaments, and cartilage by using a 4-point Likert scale according to the level of diagnostic confidence. Interchangeability of the protocols was tested under the same-reader scenario using a bootstrap percentile confidence interval. Interreader reliability and intermethod concordance were also evaluated.Despite higher image quality and diagnostic confidence for standard 2D TSE compared to 3D CAIPIRINHA SPACE TSE, the protocols were found interchangeable for diagnosing knee abnormalities, except for patellar (6.8% difference; 95% CI: 4.0, 9.6) and trochlear (3.6% difference; 95% CI: 0.8, 6.6) cartilage defects. The interreader reliability was substantial to almost perfect for 2D and 3D MRI (range κ, 0.785-1 and κ, 0.725-0.964, respectively). Intermethod concordance was almost perfect for all diagnoses (range κ, 0.817-0.986).Multicontrast 3D CAIPIRINHA SPACE TSE and standard 2D TSE protocols perform interchangeably for diagnosing knee abnormalities, except for patellofemoral cartilage defects. Despite the radiologist's preference for 2D TSE imaging, a pursuit towards time-saving 3D TSE knee MRI is justified for routine practice.• Multicontrast 3D CAIPIRINHA SPACE and standard 2D TSE protocols perform interchangeably for diagnosing knee abnormalities, except for patellofemoral cartilage defects. • Radiologists are more confident in diagnosing knee abnormalities on 2D TSE than on 3D CAIPIRINHA SPACE TSE MRI. • Despite the radiologist's preference for 2D TSE, a pursuit towards accelerated 3D TSE knee MRI is justified for routine practice.

IntroductionTubal patency testing is an essential part in the fertility workup of many subfertile women. Hysterosalpingography (HSG) has long been the test of choice in many clinics. There is evidence from a large randomised multicentre trial and from a recent meta-analysis that women who had HSG using oil soluble contrast medium (OSCM) had higher rates of ongoing pregnancy compared with women who underwent this procedure using water contrast. However, the field is moving away from HSG and nowadays hysterosalpingo-foam sonography (Hyfosy) using ultrasound guidance is considered as the first line office tubal patency test. Therefore, a large multicentre randomised clinical trial (RCT) will be initiated to evaluate if flushing the fallopian tubes with OSCM after a normal Hyfosy showing at least one patent fallopian tube will increase the live birth rate as compared with no flushing.Methods and analysisWe plan a multicentre two arm, 1:1 randomised, open-label pragmatic comparative trial in 12 Belgian centres. After informed consent, we will randomise infertile women between 18 and 40 years of age, undergoing Hyfosy as part of the fertility workup to Hyfosy with additional tubal flushing with OSCM versus Hyfosy without additional flushing. Infertility is defined as lack of conception despite 12 months of unprotected intercourse, or three cycles of donor insemination without pregnancy or three ovulatory ovulation induction cycles without pregnancy, all three in combination with at least one patent tube on Hyfosy. Primary endpoint will be live birth with conception within 6 months after randomisation.Ethics and disseminationApproval on 11 May 2021 by the Ethics Committee from ZNA Hospital Antwerp who was the central Ethics Committee for the Clinical Trial Regulation Pilot (Pilot 412) in the 12 centres. The findings from this RCT will be disseminated in peer-reviewed publications and presentations at scientific international meetings.Trial registration numbersEudraCT number: 2020-002135-30 and NCT04379973.

Simple Summary SARS-CoV-2 infection has been associated with broad dysregulation of the circulating immune system and inflammation that could persist for a long period. Chronic inflammation has been shown to play a significant role in cancer development and progression. Here we showed that several immune-related factors were altered in cancer patients who had previously been exposed to the virus. Several of these immune factors observed to be elevated even after 3 months of infection are also tumour-promoting factors. The results of this study suggest that we need to pay more attention to cancer patients who have recovered from COVID-19 for any increased rate of cancer progression. Abstract Cytokines, chemokines, and (angiogenic) growth factors (CCGs) have been shown to play an intricate role in the progression of both solid and haematological malignancies. Recent studies have shown that SARS-CoV-2 infection leads to a worse outcome in cancer patients, especially in haematological malignancy patients. Here, we investigated how SARS-CoV-2 infection impacts the already altered CCG levels in solid or haematological malignancies, specifically, whether there is a protective effect or rather a potentially higher risk for major COVID-19 complications in cancer patients due to elevated CCGs linked to cancer progression. Serially analysing immune responses with 55 CCGs in cancer patients under active treatment with or without SARS-CoV-2 infection, we first showed that cancer patients without SARS-CoV-2 infection (n = 54) demonstrate elevated levels of 35 CCGs compared to the non-cancer, non-infected control group of health care workers (n = 42). Of the 35 CCGs, 19 were common to both the solid and haematological malignancy groups and comprised previously described cytokines such as IL-6, TNF-α, IL-1Ra, IL-17A, and VEGF, but also several less well described cytokines/chemokines such as Fractalkine, Tie-2, and T cell chemokine CTACK. Importantly, we show here that 7 CCGs are significantly altered in SARS-CoV-2 exposed cancer patients (n = 52). Of these, TNF-α, IFN-β, TSLP, and sVCAM-1, identified to be elevated in haematological cancers, are also known tumour-promoting factors. Longitudinal analysis conducted over 3 months showed persistence of several tumour-promoting CCGs in SARS-CoV-2 exposed cancer patients. These data demonstrate a need for increased vigilance for haematological malignancy patients as a part of long COVID follow-up.

Background: Cancer patients are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). However, the safety and efficacy of COVID-19 vaccination in cancer patients undergoing treatment remain unclear. Patients and methods: In this interventional prospective multicohort study, priming and booster doses of the BNT162b2 COVID-19 vaccine were administered 21 days apart to solid tumor patients receiving chemotherapy, immunotherapy, targeted or hormonal therapy, and patients with a hematologic malignancy receiving rituximab or after allogeneic hematopoietic stem cell transplantation. Vaccine safety and efficacy (until 3 months post-booster) were assessed. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) antibody levels were followed over time (until 28 days after the booster) and in vitro SARS-CoV-2 50% neutralization titers (NT50) toward the wild-type Wuhan strain were analyzed 28 days after the booster. Results: Local and systemic adverse events (AEs) were mostly mild to moderate (only 1%-3% of patients experienced severe AEs). Local, but not systemic, AEs occurred more frequently after the booster dose. Twenty-eight days after the booster vaccination of 197 cancer patients, RBD-binding antibody titers and NT50 were lower in the chemotherapy group {234.05 IU/ml [95% confidence interval (CI) 122.10-448.66] and 24.54 (95% CI 14.50-41.52), respectively} compared with healthy individuals [1844.93 IU/ml (95% CI 1383.57-2460.14) and 122.63 (95% CI 76.85-195.67), respectively], irrespective of timing of vaccination during chemotherapy cycles. Extremely low antibody responses were seen in hematology patients receiving rituximab; only two patients had RBD-binding antibody titers necessary for 50% protection against symptomatic SARS-CoV-2 infection (

ispartof: CRITICAL CARE vol:25 issue:1 ispartof: location:England status: published

OBJECTIVES: Overwhelming clinical evidence exists on disturbed vascular and endothelial function in the pathophysiology of preeclampsia (PE). In a non-pregnant (NP) population, L-FMC (low-flow mediated constriction) provides insight in the 'resting' endothelial capacity in contrast to the gold standard of flow mediated dilatation (FMD), reflecting endothelial nitric oxide bioavailability.STUDY DESIGN: Longitudinal follow-up of 100 healthy pregnant (HP) women, 33 PE women and 16 NP controls with non-invasive vascular assessments. HP women were evaluated at 12 and 35 weeks of gestation and at 6 months postpartum. PE patients were assessed at diagnosis (mean 30 weeks) and 6 months postpartum.MAIN OUTCOME MEASURES: Endothelial function (L-FMC, FMD, peripheral arterial tonometry (PAT)) and arterial stiffness (pulse wave velocity (PWV) and analysis (PWA)) were measured at the different visits and compared between groups.RESULTS: Overall endothelial dysfunction is present in PE (FMD HP 9.09 ± 4.20 vs PE 5.21 ± 4.47, p = 0.0004; L-FMC HP -1.90 ± 2.66 vs PE -0.40 ± 2.09, p = 0.03). L-FMC gradually elevates during the course of a HP (1st trim -0.31 ± 1.75 vs 3rd trim -1.97 ± 3.02, p 0.05).CONCLUSION: PE is characterized by dysfunction of both resting and recruitable endothelial capacity. This study offers new insights in different aspects of endothelial function in pregnancy, since L-FMC reflects an adaptation in HP that is absent in PE.

Background: The SARS-CoV-2 pandemic has a far-reaching impact on healthcare. Cancer patients in particular were regarded as vulnerable and oncology departments drastically modified their Care systems and established new priorities. We evaluated the impact of SARS-CoV-2 on the activity of a single cancer center; and we studied patients’ perspectives of the preventive institutional or governmental safety measures.Methods: We performed a retrospective analysis of (i) Volumes of Oncological activities (2020 versus 2019), (ii) patients’ perception rate of the preventive measures, (iii) patients’ SARS-Cov-2 infections, clinical signs thereof and (iv) new diagnoses made during the SARS-CoV-2 pandemic. Results: As compared with a similar timeframe in 2019 the overall activity in total numbers of outpatient chemotherapy administrations and specialist visits, based on weekly average of daily accesses was not statistically different; while inpatient admissions decreased for both medical oncology and thoracic oncology (18% (p=0.0018) and 44% (p85%). However, only 46.2% of responding patients regarded telemedicine, although widely deployed, as an efficient surrogate to a consultation. Thirty-three patients developed SARS-CoV-2, 27 were hospitalized and 11 died within this time frame. These infected patients were younger, current smokers and suffered more comorbidities.Conclusions: This retrospective cohort analysis demonstrates that continuation of active cancer therapy and specialist visits is feasible and safe after implementation of population-wide, institutional and department specific safety measures. Substantial decreases in diagnosis of solid tumors were recorded. To manage the backlog of belated diagnoses, while providing continued state-of-the-art cancer care during this prolonged health crisis, we need policy interventions to adapt the health care system and allow telemedicine to fulfill a more prominent role.

Purpose The aim of this study is to investigate clinical and magnetic resonance imaging (MRI) outcomes after anterior cruciate ligament (ACL) repair using the suture tape augmentation (STA) technique. Methods This prospective interventional case series included 35 patients who underwent STA ACL repair and were all followed up for 2 years. The ACL rupture was between 4 and 12 weeks old and per-operatively confirmed repairable. The International Knee Documentation Committee (IKDC), and Lysholm and Tegner scores were collected together with return to work (RTW), return to sport (RTS), re-rupture, and re-intervention rate. Lachman testing was performed and ACL healing was evaluated on MRI using a grading scale based on the ACL’s morphology and signal intensity with grade 1 representing good ACL healing and grade 3 representing poor ACL healing. Results The number of patients who returned to their pre-rupture level for IKDC, Lysholm, and Tegner scores at 2 years of follow-up are 17/26 (65.4%), 13/25 (52.0%), and 18/27 (66.7%) patients, respectively. Median RTW and RTS periods were 5.5 weeks (range 0–32 weeks) and 6 months (range 2–22 months), respectively. The Lachman side-to-side difference decreased significantly (P

Background: Cancer patients are at higher risk of developing severe COVID-19. However, safety and efficacy of COVID-19 vaccination in cancer patients undergoing treatment is unclear. Methods: In this interventional prospective multi-cohort study, priming and booster doses of the BNT162b2 COVID-19 vaccine were administered 21 days apart to solid tumor patients receiving chemotherapy, immunotherapy, targeted- or hormonal therapy, and patients with a hematologic malignancy receiving rituximab or after allogeneic hematopoietic stem cell transplantation. Primary endpoint was anti-SARS-CoV-2 receptor binding domain (RBD) antibody level at 28 days post-booster. Anti-RBD IgG titers above 200 IU/ml was used to define high-responders as it leads to a neutralization response required for 50% protection against symptomatic SARS-CoV-2 infection in 268 independent subjects. Secondary endpoints included self-reported adverse events (AEs), antibody response over time and number of breakthrough infections after vaccination. Findings: 28 days post-booster vaccination of 197 cancer patients, antibody response was lower in the hematological cohort (geometric mean titer (GMT) 17·61 IU/mL [95% CI 7·17-43·24]) and the chemotherapy cohort (GMT 234·05 IU/mL [95% 95%CI 122·10-448·66]) when compared to healthy individuals (n=40; GMT 1844·93 IU/mL [95% CI 1383·57-2460·14]), irrespective of timing of vaccination during chemotherapy cycles. Only 55% and 7% of patients receiving chemotherapy or rituximab could be categorized as high-responders at 28 days post-booster. During the study period, five subjects tested positive for SARS-CoV-2 infection, including three after full vaccination. Local and systemic AEs were mostly mild to moderate, with only 1-3% of patients experiencing severe AEs. Local, but not systemic, AEs occurred more frequently after booster than after priming dose. Interpretation: The BNT162b2 vaccine is well-tolerated in cancer patients under active treatment. However, the antibody response of immunized cancer patients was delayed and diminished, mainly in patients receiving chemotherapy or rituximab, resulting in breakthrough infections. Trial Registration: EudraCT number 2021-000300-38 Funding: The regulatory sponsor was the Antwerp University Hospital (EudraCT number 2021-000300-38). The trial was funded by the Belgian Government through Sciensano (COVID-19_SC004, COVID- 19_SC059, COVID-19_SC061). Declaration of Interest: MP declares to have an advisory role within Remedus, all other authors declare no competing interests. Ethical Approval: The study was approved by the local ethics committee and was executed in accordance with Good Clinical Practice and the Declaration of Helsinki (ICH GCP E6(R2)).

Purpose Does IDEF mapping help monitor the technical process of IUI and explore the potential improvements which might contribute to increased pregnancy and live birth rates? Method Retrospective analysis of 1729 homologous IUI cycles of couples attending a fertility clinic in a university hospital setting. Standardized conventional semen parameters were analyzed and the semen samples prepared via discontinuous density gradient centrifugation. Results There was no significant association between sperm concentration, motility and morphology (analysis phase), and pregnancy outcome. Only female and male ages were significantly associated with the pregnancy outcome. There was a significant difference in the odds on clinical pregnancies and live births when analysis was

Background Telehealth modalities were introduced during the SARS-CoV-2 pandemic to assure continuation of cancer care and maintain social distance. Methods This is a retrospective cohort analysis of our telehealth expansion programme. We adapted two existing patient-reported outcome (PRO) telemonitoring tools that register and (self-)manage toxicities to therapy, while screening for SARS-CoV-2-related symptoms. Outpatients from a tertiary cancer centre were enrolled. The adapted PRO interface allowed for uniform registration of SARS-CoV-2-related symptoms and effective triage of patients at home where we also implemented systematic throat washings, when available. Results Three hundred and sixty patients registered to the telemonitoring systems from March 13 to May 15, 2020. Four prespecified SARS-CoV-2 alarms resulted in three patients with positive PCR testing. Other Covid-19 symptoms (fever 5× and cough 2×) led to pretreatment triage resulting in 1 seroconversion after initial negative testing. One of the 477 throat washings proved positive. Conclusions The rapid adoption of an amended PRO (self-)registrations and toxicity management system was feasible and coordinated screening for Covid-19. Continued clinical cancer care was maintained, with significant decreased waiting time. The systemic screening with throat washings offered no real improvement.

Objectives The purpose of this study was to assess the technical feasibility of 3-dimensional (3D) super-resolution reconstruction (SRR) of 2D turbo spin echo (TSE) knee magnetic resonance imaging (MRI) and to compare its image quality with conventional 3D TSE sampling perfection with application optimized contrast using different flip angle evolutions (SPACE) MRI. Materials and Methods Super-resolution reconstruction 2D TSE MRI and 3D TSE SPACE images were acquired from a phantom and from the knee of 22 subjects (8 healthy volunteers and 14 patients) using a clinical 3-T scanner. For SRR, 7 anisotropic 2D TSE stacks (voxel size, 0.5 × 0.5 × 2.0 mm3; scan time per stack, 1 minute 55 seconds; total scan time, 13 minutes 25 seconds) were acquired with the slice stack rotated around the phase-encoding axis. Super-resolution reconstruction was performed at an isotropic high-resolution grid with a voxel size of 0.5 × 0.5 × 0.5 mm3. Direct isotropic 3D image acquisition was performed with the conventional SPACE sequence (voxel size, 0.5 × 0.5 × 0.5 mm3; scan time, 12 minutes 42 seconds). For quantitative evaluation, perceptual blur metrics and edge response functions were obtained in the phantom image, and signal-to-noise and contrast-to-noise ratios were measured in the images from the healthy volunteers. Images were qualitatively evaluated by 2 independent radiologists in terms of overall image quality, edge blurring, anatomic visibility, and diagnostic confidence to assess normal and abnormal knee structures. Nonparametric statistical analysis was performed, and significance was defined for P values less than 0.05. Results In the phantom, perceptual blur metrics and edge response functions demonstrated a clear improvement in spatial resolution for SRR compared with conventional 3D SPACE. In healthy subjects, signal-to-noise and contrast-to-noise ratios in clinically relevant structures were not significantly different between SRR and 3D SPACE. Super-resolution reconstruction provided better overall image quality and less edge blurring than conventional 3D SPACE, yet the perceived image contrast was better for 3D SPACE. Super-resolution reconstruction received significantly better visibility scores for the menisci, whereas the visibility of cartilage was significantly higher for 3D SPACE. Ligaments had high visibility on both SRR and 3D SPACE images. The diagnostic confidence for assessing menisci was significantly higher for SRR than for conventional 3D SPACE, whereas there were no significant differences between SRR and 3D SPACE for cartilage and ligaments. The interreader agreement for assessing menisci was substantial with 3D SPACE and almost perfect with SRR, and the agreement for assessing cartilage was almost perfect with 3D SPACE and moderate with SRR. Conclusions We demonstrate the technical feasibility of SRR for high-resolution isotropic knee MRI. Our SRR results show superior image quality in terms of edge blurring, but lower image contrast and fluid brightness when compared with conventional 3D SPACE acquisitions. Further contrast optimization and shortening of the acquisition time with state-of-the-art acceleration techniques are necessary for future clinical validation of SRR knee MRI.

Despite the existing methods, a trend towards a later initiation and completion of toilet training has been seen in Western society. This study is the first to investigate prospectively the efficacy of intensive group toilet training in daycare centres. The primary outcome of interest is the duration until the child is toilet trained. A cluster randomised controlled trial was established in daycare centres; clusters of participants were randomly allocated to an intervention or control group. Intervention group was subjected to an intensive toilet training session. Innovative aspects of this toilet training method were a 2-h training on two consecutive days, carried out in small groups in daycare centres. Parents of children in the control group were encouraged to start TT in their own manner. Children were monitored until they were considered to be fully toilet trained during the day. Median toilet training duration in the intervention group was 2 weeks compared to 5 weeks in controls (p value log rank test = 0.007). The hazard of being clean during the follow-up of 6 weeks was twice as high in the intervention compared to controls (p = 0.018).Conclusion: The intervention had a significant influence on the duration of toilet training in healthy children, with a median duration of 2 weeks. Our findings are clinically relevant for daycare educators, having a considerable responsibility in the development of children.Trial Registration Number: ClinicalTrials.gov NCT04221776. What is Known: • Despite different existing methods, a later initiation of toilet training has been seen in Western society and coherent to this an increasing age of acquiring full bladder control. • Child daycare centres have a growing role in the toilet training process. What is New: • This is the first prospective report describing the results of a new method of toilet training healthy children in small groups in daycare centres. • The intervention had a significant influence on the duration of toilet training, with a median duration of 2 weeks.

Introduction We investigated whether a web-based cognitive training video game is an effective approach to improve cognitive decline in combination with our standard of care for rehabilitation of breast cancer (BC) patients. Materials and methods Self-selected BC patients between 18 and 71 years old complaining of disturbing cognitive impairment were studied. The patients received access to a web-based internet video game and online cognitive assessments (Aquasnap, Cambridge, MyCQ™). The early intervention group (n = 23) had a training program of 6 months of at least three times a week for a minimum of 60 min of game playing per week at home in addition to standard of care rehabilitation. The delayed intervention (n = 23) received standard of care for three months, followed by three months of similar MyCQ training. Outcome measures were the MyCQ (sub)scores and Activity of Daily Life (ADL), mood, subjective cognition and functional cognitive status measured by classic neuropsychological tests. Results At baseline the means for CFQ (a measure of self-reported cognitive failure), anxiety, PSQI and self-reflectiveness were beyond normal range in both groups. CFQ improved significantly better in the intervention group (p = 0.029). Combining the evolution over time in the entire population a significant improvement was seen for overall MyCQ score, level of fear, physical and emotional role limitation, and health change (all p < 0.05), but self-reflectivess deteriorated (p < 0.05)). Significant differences in the various MyCQ subtests over time were: improved speed in choice reaction time, visual memory recognition, N back 1 and 2, coding, trail making test B, improved accuracy of N back 1 and 2 (all p < 0.05). Conclusion A program of cognitive training improves cognitive functioning over time. “Aquasnap” has a beneficial effect on the perception of subjective cognitive functioning (CFQ) but the exact role of video gaming in this process remains uncertain.

To longitudinally monitor remodeling of human autograft following anterior cruciate ligament (ACL) reconstruction with DTI. Twenty-eight patients underwent DTI follow-up at 3, 8, and 14 months after clinically successful ACL reconstruction with tendon autograft. Among these, 18 patients had a concomitant lateral extra-articular procedure (LET). DTI data from 7 healthy volunteers was also obtained. Diffusion parameters (fractional anisotropy, FA; mean diffusivity, MD; axial diffusivity, AD; and radial diffusivity, RD) were evaluated within the fiber tractography volumes of the ACL graft and posterior cruciate ligament (PCL) in all patients. Data were analyzed using a linear mixed-effects model with post hoc testing using Bonferroni-Holm correction for multiple testing. The effect of additional LET was studied. The ACL graft showed a significant decrease of FA over time (F = 4.00, p = 0.025), while the diffusivities did not significantly change over time. For PCL there were no significant DTI changes over time. A different evolution over time between patients with and without LET was noted for all diffusivity values of the ACL graft with reduced AD values in patients with LET at 8 months postoperatively (p = 0.048; adjusted p = 0.387). DTI metrics of the ACL graft differed largely from both native ACL and tendon at 14 months postoperatively. Our study has shown the potential of DTI to longitudinally monitor the remodeling process in human ACL reconstruction. DTI analysis indicates that graft remodeling is incomplete at 14 months postoperatively. • DTI can be used to longitudinally monitor the remodeling process in human ACL reconstruction. • DTI analysis indicates that autograft remodeling is incomplete at 14 months postoperatively. • DTI may be helpful for evaluating new ACL treatments.

Objective It is recommended that cancer survivors incorporate physical activity into their daily lives after in-hospital rehabilitation. However, there is a lack of training programmes focusing on the specific needs of cancer survivors. TriaGO! - an 8-month intervention study of aerobic endurance training for cancer survivors - was therefore examined. The training programme aims to meet the participants’ physical needs and provide socio-emotional support, in the form of an exercise programme that challenges participants to aim to compete in an Olympic- distance triathlon (1,000 m swimming, 45 km cycling, 10 km running) after 8 months’ of training. Methods The TriaGO! training programme was provided to in-hospital rehabilitated cancer survivors (n = 12). Each patient invited a healthy friend or family member to train with them (a so called buddy (n = 12)). The 8-month programme involves supervised training sessions, combining cycling, swimming and running, which progress in frequency, duration and intensity. Physical health was measured at the start, 4 and 8 months, using objective parameters of aerobic fitness, muscular fitness and body composition. Results A total of 22 out of 24 participants successfully completed the training programme and the triathlon. Both the cancer survivors and their buddies showed significant improvements in physical health. Cancer survivors showed improvements in aerobic fitness, as increases in VO2max and VO2peak of 5.5 ml.kg−1.min−1 and 0.26 ml.min−1 respectively (p

Background: Over the past 100 years, toilet training (TT) methods have oscillated between rigid and permissive programs, but despite the existing methods, a trend towards a later initiation and completion of TT has been seen in Western society (3, 8-18) . This study is the first to investigate prospectively the efficacy of intensive TT in small groups in daycare centers . The primary outcome of interest is the duration until the child is toilet trained. Methods: A cluster randomized controlled trial was established in daycare centers, clusters of participants were randomly allocated to an intervention (IG) or control group (CG). The IG was subjected to an intensive TT group session. In the CG, parents of the children were encouraged to start TT in their own manner. The TT process was monitored until the child was considered to be fully toilet trained during the day. Findings: The median TT duration in the IG was 2 weeks compared to 5 weeks in controls (p-value log rank test = 0·007). The hazard of being clean during the follow up of 6 weeks was twice as high in the IG compared to the CG (p=0·018) and almost three times higher in girls compared to boys. Interpretation Innovative aspects of this TT method were a two-hour training on two consecutive days, carried out in small groups in daycare centers. This experimental intervention of group TT had a significant influence on the duration of TT in healthy children, with a median duration of 2 weeks. Our findings are clinically relevant for daycare educators, becoming more accepted as a third educational environment in the development of children. Trial Registration: nr. B300201630079). Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Ethical Approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Conflicts of Interest: All authors declare that they have no conflict of interest.

PurposeThe treatment of acute anterior cruciate ligament (ACL) ruptures with a repair technique has recently regained interest. A novel ACL repair technique was described using Independent Suture Tape Reinforcement with 2-year follow-up results.MethodsForty-two consecutive patients with an acute ACL rupture undergoing repair using this technique were followed up for a minimum of 2years. Patients with mid-substance, distal ACL ruptures, poor ACL tissue quality or retracted ACL remnants as well as patients with multi-ligament injuries were excluded. Knee Injury and Osteoarthritis Outcome Score (KOOS), Visual Analogue Pain Scale (VAS-pain), Veterans RAND 12 Item Health Survey (VR-12) and the Marx Activity scale were collected by online questionnaires. Two-year postoperative patients were asked by telephone if they had experienced a rerupture.ResultsAll the KOOS subscales improved significantly in comparison to the preoperative score. The largest improvement of all scores was seen at 3months postoperatively which is significant in all cases. The KOOS sport and recreation showed a meaningful change and the largest improvement of the KOOS subscales at 3months postoperatively, as well as the highest total improvement at 1year postoperatively compared to preoperatively. The VAS-pain and VR-12 physical score improved significantly, however the Marx activity scale decreased significantly in comparison to preoperative scores. Two patients reported a rerupture (4.8%, CI 1.7-11.2%).ConclusionsThis is the first case series that described the 2-year follow-up results of patients with an acute, proximal ACL rupture, treated with the Independent Suture Tape Reinforcement repair technique. A meaningful KOOS sport and recreation change and significant improvements in the KOOS, VAS-pain and VR-12 physical scores as well as a significant decrease of the Marx activity scale in comparison to preoperative scores are demonstrated. Two of the 42 patients (4.8%) reported an ACL rerupture. Repair with this technique could be clinically relevant as a treatment option for patients with an acute, proximal ACL rupture which is not retracted and of good tissue quality.Level of evidenceIV.

OBJECTIVES: Ischaemia-reperfusion injury is a necessary part of organ transplantation and a key determinant of both acute and chronic graft failure. We have assessed the contribution of endothelial nitric oxide synthase (eNOS) and eNOS uncoupling to oxidative and nitrosative stress formation during lung ischaemia-reperfusion injury dependent on ischaemia time.METHODS: Forty eNOS wild-type mice (eNOS(+/+)) and 40 eNOS knock-out mice (eNOS(-/-)) received either a sham thoracotomy or 60 or 90 min of ischaemia, followed by 0, 1 or 24 h of reperfusion. Lung tissue was analysed with electron spin resonance for NO production and reactive oxygen species content. Protein nitrosation, eNOS and eNOS uncoupling were determined using western blotting. In peripheral blood, arterial blood gases were taken and reactive oxygen species content was determined.RESULTS: eNOS(+/+) mice had lower reactive oxygen species production in their peripheral circulation but worse blood gas values after 1 h of reperfusion. Lung tissue of eNOS(-/-) mice showed lower reactive oxygen species and NO production and lower protein nitrosation compared with wild-type mice. Longer ischaemia times result in more elaborate oxidative and nitrosative stress dependent on eNOS genotype. Structural eNOS uncoupling was present after 60 min of ischaemia but diminished after 90 min of ischaemia.CONCLUSIONS: eNOS uncoupling may contribute to lung ischaemia-reperfusion injury and inflammation. This ultimately leads to worse clinical outcome. Stabilizing eNOS may therefore be a new approach to extend pulmonary graft survival.

Purpose To determine the effects of the sodium content of maintenance fluid therapy on cumulative fluid balance and electrolyte disorders. Methods We performed a randomized controlled trial of adults undergoing major thoracic surgery, randomly assigned (1:1) to receive maintenance fluids containing 154 mmol/L (Na154) or 54 mmol/L (Na54) of sodium from the start of surgery until their discharge from the ICU, the occurrence of a serious adverse event or the third postoperative day at the latest. Investigators, caregivers and patients were blinded to the treatment. Primary outcome was cumulative fluid balance. Electrolyte disturbances were assessed as secondary endpoints, different adverse events and physiological markers as safety and exploratory endpoints. Findings We randomly assigned 70 patients; primary outcome data were available for 33 and 34 patients in the Na54 and Na154 treatment arms, respectively. Estimated cumulative fluid balance at 72 h was 1369 mL (95% CI 601–2137) more positive in the Na154 arm (p 109 mmol/L under Na154 (24/35 patients, 68.6%) than under Na54 (4/34 patients, 11.8%) (p