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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154 mmol/L of sodium lead to a more positive fluid balance than a regimen containing 54 mmol/L. We report different unpublished data on the renal handling of the imposed sodium bur -dens with specific attention to the resulting fluid and sodium balances.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.

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.

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

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

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

Background Spine surgery is associated with considerable postoperative pain and can be challenging to treat. A loco-regional technique suitable for spine surgery should cover the dorsal root of the spinal nerves at the levels where surgery is performed. The erector spinae block is a loco-regional technique with promising results and was recently described at the thoracic level. There are no randomized trials of this technique on a lumbar level. This study tests the hypothesis that the 24-h postoperative morphine consumption is significantly lower in patients undergoing posterior lumbar inter-body fusion surgery with a lumbar erector spinae (LUMBES) block when compared with a sham block. Methods This prospective randomized double-blind multicenter study will randomly allocate 80 adult patients undergoing elective posterior lumbar inter-body fusion surgery during general anesthesia to one of two groups as follows: (1) bilateral erector spinae block (20 mL 0.25% levobupivacaine) or (2) bilateral sham block (20 mL NaCl 0.9%). Our primary endpoint is 24-h postoperative morphine consumption. Secondary endpoints include 72-h morphine consumption, intraoperative sufentanil dosage, postoperative pain scores at regular time intervals both at rest and during movement, time to first postoperative mobilization, and the Quality of Recovery 40 survey score. Discussion The LUMBES trial is a pragmatic clinical study that will provide evidence of whether a bilateral lumbar erector spinae block is effective in reducing 24-h postoperative morphine consumption in patients undergoing lumbar inter-body fusion surgery. If this hypothesis is confirmed, this finding could contribute to more widespread implementation of this technique. Trial registration Local ethics committee B300201837508, ClinicalTrials.gov identifier: NCT03825198. Registered on 31 Jan 2019. Electronic supplementary material The online version of this article (10.1186/s13063-019-3541-y) contains supplementary material, which is available to authorized users.

Purpose TUNEL assay is the most common, direct test for sperm chromatin integrity assessment. But, lack of standardized protocols makes interlaboratory comparisons impossible. Consequently, clinical thresholds to predict the chance of a clinical pregnancy also vary with the technique adopted. This prospective study was undertaken to assess the incidence of sperm DNA fragmentation in a subfertile population and to establish threshold values of normality as compared to a fertile cohort, both before and after density gradient centrifugation in the total and vital fractions. Method Men presenting at a university hospital setup for infertility treatment. DNA damage via TUNEL assay was validated on fresh semen samples, as conventional semen parameters, to reduce variability of results. Results Total DNA fragmentation in the neat semen was significantly higher in the subfertile group, but the vital fraction was not significantly different between the two cohorts. After gradient centrifugation, DNA fragmentation increased significantly in the total fraction of the subfertile group but decreased significantly in the vital fraction. In the fertile cohort, there was a non-significant increase in total fragmentation and in the vital fraction the trend was unclear. Conclusions Estimating total and vital sperm DNA fragmentation, after density gradient centrifugation, increased both the sensitivity and the specificity, thereby lowering the number of false negatives and false positives encountered. These findings provide opportunities to investigate the significance of the total and the vital fractions after different assisted reproductive technologies.

Management of fever in prolonged profound neutropenia remains challenging with many possible infectious and non-infectious causes. We investigated whether procalcitonin (PCT) is superior to C-reactive protein (CRP) in discriminating between different etiologies of fever in this setting. CRP and PCT were tested daily during 93 neutropenic episodes in 66 patients. During this study period 121 febrile episodes occurred and were classified into four categories based on clinical and microbiological findings: microbiologically documented infection (MDI); clinically documented infection (CDI); proven or probable invasive fungal disease (IFD); fever of unknown origin (FUO). Values of PCT and CRP at fever onset as well as 2 days later were considered for analysis of their performance in distinguishing etiologies of fever. At fever onset no significant difference in PCT values was observed between different etiologies of fever, whereas median CRP values were significantly higher in case of IFD (median 98.8 mg/L vs 28.8 mg/L, p=0.027). Both PCT and CRP reached their peak at a median of 2 days after fever onset. Median PCT values on day 2 showed no significant difference between etiologies of fever. Median CRP values on day 2 were significantly higher in IFD (median 172 mg/L versus 78.4 mg/L, p=0.002). In MDI median CRP values rose > 100 mg/L, whereas they did not in CDI or FUO. PCT has no added value over CRP for clinical management of fever in prolonged profound neutropenia. When performing reassessment 2 days after fever onset, CRP has better discriminatory power between etiologies of fever.

BackgroundThe current gold standard for the treatment of an anterior cruciate ligament (ACL) rupture is reconstruction with tendon graft. Recently, two surgical ACL repair techniques have been developed for treating an acute ACL rupture: Dynamic Intraligamentary Stabilization (DIS, Ligamys®) and Internal Brace Ligament Augmentation (IBLA,InternalBrace™). We will conduct a single-blind, multi-center, randomized controlled trial which compares DIS, IBLA and reconstruction for relative clinical efficacy and economic benefit.MethodsSubjects, aged 18–50 years, with a proximal, primary and repairable ACL rupture will be included. DIS is preferably performed within 4 weeks post-rupture, IBLA within 12 weeks and reconstruction after 4 weeks post-rupture. Patients are included in study 1 if they present within 0–4 weeks post-rupture and surgery is feasible within 4 weeks post-rupture. Patients of study 1 will be randomized to either DIS or IBLA. Patients are included in study 2 if they present after 4 weeks post-rupture and surgery is feasible between 5 and 12 weeks post-rupture. Patients of study 2 will be randomized to either IBLA or reconstruction. A total of 96 patients will be included, with 48 patients per study and 24 patients per study arm. Patients will be followed-up for 2 years. The primary outcome is change from baseline (pre-rupture) in International Knee Documentation Committee score to 6 months post-operatively. The main secondary outcomes are the EQ-5D-5 L, Tegner score, Lysholm score, Lachman test, isokinetic and proprioceptive measurements, magnetic resonance imaging outcome, return to work and sports, and re-rupture/failure rates. The statistical analysis will be based on the intention-to-treat principle. The economic impact of the surgery techniques will be evaluated by the cost-utility analysis. The LIBRƎ study is to be conducted between 2018 and 2022.DiscussionThis LIBRƎ study protocol is the first study to compare DIS, IBLA and ACL reconstruction for relative clinical efficacy and economic benefit. The outcomes of this study will provide data which could aid orthopaedic surgeons to choose between the different treatment options for the surgical treatment of an acute ACL rupture.Trial registrationThis study is registered at ClinicalTrials.gov;NCT03441295. Date registered 13.02.2018.

Pterygium is a common eye disease, linked to an increased exposure to UV radiation and dry environments. The associated pathology culminates in visual impairment and, in some rare cases, blindness. However, there remains a lot of uncertainty concerning the pathogenesis of this fibrovascular lesion. As the composition of the tear film provides a reflection into the pathological changes at the ocular surface, tear analysis represents an ideal approach to gain insight in the progression of disease following pterygiectomy. This study enrolled 19 patients and age/gender-matched healthy controls. Tear film levels of interleukin- (IL-) 6, IL-8, and vascular endothelial growth factor (VEGF) were investigated over time, and preoperative concentrations were linked to corneal neovascularization and pterygium size. Diminished tear film levels were found in unilateral patients who show no clinical signs of pterygium recurrence over a period of one year. Hence, our results highlight the potential of using the course of IL-6, IL-8, and VEGF levels in tears as biomarkers for recovery. In addition, when focusing on the affected eyes (i.e., primary and recurrent pterygium), we detected fold changes in preoperative cytokine concentrations to correspond with disease severity. As our proposed biomarkers did not reveal a linear relationship with corneal neovascularization nor the invasive behaviour of pterygium, no exact role in the pterygium pathology could be established. Hence, our data point to these factors being contributors rather than decisive players in the pathological processes.

Purpose To assess anterolateral complex (ALC) injuries in patients with acute anterior cruciate ligament (ACL) rupture on magnetic resonance imaging (MRI). Methods Patients with acute ACL rupture who underwent ACL surgery between 2015 and 2017 and underwent MRI within 6 weeks of the initial trauma were included. Two radiologists assessed magnetic resonance images retrospectively for the status of the ALC, including the iliotibial band (ITB), Kaplan fibers, and anterolateral ligament (ALL), as follows: grade 0, normal; grade 1, periligamentous edema; grade 2, partial tear; and grade 3, complete tear. The findings were analyzed using the Friedman test and weighted κ values. Results Sixty-nine MRI scans were reviewed. Of the 69 patients, 51% had associated injuries to the ITB (grade 1, n = 31; grade 2, n = 4), 33% had associated injuries to the Kaplan fibers (grade 1, n = 21; grade 2, n = 2), and 57% had associated injuries to the ALL (grade 1, n = 12; grade 2, n = 22; grade 3, n = 5). We found a significant difference in the frequency and grading between ITB, Kaplan fiber, and ALL injuries (P ≤ .032). Inter-reader agreement for assessing the ALC on MRI was almost perfect (κ ≥ 0.922). Conclusions On the basis of MRI analysis, ALL injuries were found with varying degrees of severity and intensity with noted injuries to associated surrounding fibers in patients with acute ACL rupture. Level of Evidence Level IV, case series.