Abdominal aneurysm sac thrombus CT density and volume after EVAR: which association with underlying endoleak?

BACKGROUND: Our aim was to analyse abdominal aneurysm sac thrombus density and volume on computed tomography (CT) after endovascular aneurysm repair (EVAR). METHODS: Patients who underwent EVAR between January 2005 and December 2010 and had at least four follow-up CT exams available over the first five years of follow-up were included in this retrospective single-centre study. Thrombus density and aneurysm sac volume were calculated on unenhanced CT scans. Linear mixed models were used for data analysis. RESULTS: Out of 82 patients, 44 (54%) had an endoleak on post-EVAR contrast-enhanced CT. Thrombus density significantly increased over time in both the endoleak and non-endoleak groups, with a slope of 0.159 UH/month (95% confidence interval [CI] 0.115-0.202), p < 0.0001) and 0.052 UH/month (95% CI 0.002-0.102, p = 0.041). In patients without endoleak, a significant decrease in aneurysm sac volume was identified over time (slope -0.891 cc/month, 95% CI -1.200 to -0.581); p < 0.001) compared to patients with endoleak (slope 0.284 cc/month, 95% CI -0.031 to 0.523, p = 0.082). The association between thrombus density and aneurysm sac volume was positive in the endoleak group (slope 1.543 UH/cc, 95% CI 0.948-2.138, p < 0.001) and negative in the non-endoleak group (slope -1.450 UH/cc, 95% CI -2.326 to -0.574, p = 0.001). CONCLUSION: We observed a progressive increase in thrombus density of the aneurysm sac after EVAR in patients with and without endoleak, more pronounced in patients with endoleak. The association between aneurysm volume and thrombus density was positive in patients with and negative in those without endoleak. RELEVANCE STATEMENT: A progressive increase in thrombus density and volume of abdominal aortic aneurysm sac on unenhanced CT might suggest underlying endoleak lately after EVAR. KEY POINTS: Thrombus density of the aneurysm sac after EVAR increased over time. Progressive increase in thrombus density was significantly associated to the underlying endoleak. The association between aneurysm volume and thrombus density was positive in patients with and negative in those without endoleak.

Newly Designed, Self-Expanding Large-Bore Nitinol Stents for Symptomatic Central Venous Stenosis: Technical and Long-Term Clinical Outcome.

PURPOSE: To retrospectively analyze the technical and long-term clinical outcome of angioplasty and stenting using the Venovo™ venous stent for the treatment of malignant and benign superior vena cava (SVC) occlusive disease. MATERIALS AND METHODS: Consecutive patients treated with the Venovo™ venous stent for SVC occlusive disease were included. SVC obstruction symptoms were classified according to the Kishi score. The Wilcoxon signed-rank test was used for testing significance of changes. Technical success, defined as correct placement of the stent, completely covering and re-expanding the obstruction, between groups was tested using the Fisher exact test. Overall survival was calculated using the Kaplan-Meier method. RESULTS: Fifty-five patients underwent stent insertion for symptomatic benign (n = 13; 24%) or malignant (n = 42; 76%) SVC occlusive disease. A significant drop in Kishi score, mean 3.91 before versus mean 1.02 after the procedure (P < 0.0001), was observed. In one patient (1.8%), an additional balloon-expandable stent was needed to manage incomplete expansion of the nitinol stent. In one patient, a procedure-related lung embolic complication was noted. Early thrombotic occlusion of the stent occurred in one patient. Late symptomatic restenosis occurred in 3 patients. Overall primary stent patency and primary-assisted stent patency were 86% (95% CI 66-95) and 97% (95% CI 83-100) at 1-year follow-up and 98% (95% CI 87-100), 98% (87-100) at 2-year follow-up, respectively. CONCLUSION: In this retrospective analysis, angioplasty and stent placement using the Venovo™ venous stent is safe and clinically effective for the treatment of both benign and malignant SVC occlusive disease. Reintervention for symptomatic restenosis is rare.

Baseline neutrophil-to-eosinophil-ratio and outcome in metastatic clear-cell renal cell carcinoma treated with nivolumab or ipilimumab/nivolumab.

BACKGROUND AND PURPOSE: This study aims to evaluate neutrophil-to-eosinophil ratio (NER) as a prognostic and/or predictive biomarker in metastatic clear cell renal cell carcinoma (m-ccRCC) treated with nivolumab or ipilimumab/nivolumab. PATIENTS/MATERIALS AND METHODS: We performed a retrospective study on m-ccRCC patients treated with nivolumab or ipilimumab/nivolumab (2012-2022). Baseline NER was calculated and correlated with clinical outcomes: response rate (RR), progression free survival (PFS) and overall survival (OS). Corresponding transcriptomic data were analysed. RESULTS: We included 201 m-ccRCC patients, 76 treated with ipilimumab/nivolumab and 125 with nivolumab. Baseline NER was statistically significantly associated with International Metastatic RCC Database Consortium (IMDC) risk groups. Increased NER was associated with shorter PFS and OS in the total patient series and nivolumab-treated patients. In patients treated with ipilimumab/nivolumab, increased NER was only statistically significantly associated with shorter OS. The impact of baseline NER on PFS and OS was independent of IMDC risk stratification. No clear correlation was found between baseline NER and RECIST response or maximal tumour shrinkage. In two additional databases, NER was also associated with PFS and OS in first-line vascular-endothelial-growth-factor-receptor tyrosine-kinase-inhibitors (VEGFR-TKIs), but not to disease-free survival in the post-nephrectomy setting. Lower NER was associated with intratumoural molecular features possibly associated with better outcome on immune checkpoint inhibitors. INTERPRETATION: Lower baseline NER is associated with better PFS and OS, independent of IMDC risk score, in m-ccRCC patients treated with ipilimumab/nivolumab or nivolumab. It correlates with intratumoural molecular features possibly associated with better outcome on immune checkpoint inhibitors. The predictive power of this biomarker is probably limited and insufficient for patient selection.

Effect of Radical Prostatectomy on Survival for Men with High-risk Nonmetastatic Prostate Cancer Features Selected According to STAMPEDE Criteria: An EMPaCT Study.

BACKGROUND AND OBJECTIVE: A meta-analysis of two randomized STAMPEDE platform trials revealed that 3 yr of abiraterone acetate in addition to androgen deprivation therapy and radiation therapy significantly improved metastasis-free and overall survival (OS) in high-risk nonmetastatic prostate cancer (PCa) and should be considered a new standard of care. The aim of our study was to assess long-term cancer-specific survival (CSS) and OS for surgically treated patients with newly diagnosed nonmetastatic node-negative PCa meeting the STAMPEDE criteria for high risk. METHODS: This was a retrospective, multicenter cohort study of patients with European Association of Urology (EAU) high-risk PCa who underwent radical prostatectomy and extended pelvic lymph node dissection. CSS was assessed using cumulative incidence curves and the Kaplan-Meier method was used to evaluate OS. We used a Fine and Gray model to evaluate the prognostic value of STAMPEDE high-risk factors (SHRFs) for CSS, and a Cox proportional-hazards model to assess the association of SHRFs with OS. KEY FINDINGS AND LIMITATIONS: A total of 2994 patients with EAU high-risk PCa were divided into groups with 0, 1, 2, or 3 SHRFs. The 10-yr survival estimates for patients with 0-1 versus 2-3 SHRFs were 95% versus 82% for CSS and 81% versus 64% for OS (both p < 0.0001). In comparison to patients with 0 SHRFs, hazard ratios were 1.2 (p = 0.5), 3.9 (p < 0.0001), and 5.5 (p < 0.0001) for CSS, and 1.1 (p = 0.4), 2.2 (p < 0.0001), and 2.5 (p = 0.0004) for OS for patients with 1, 2, and 3 SHRFs, respectively. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our results confirm that the STAMPEDE high-risk criteria identify a subgroup of patients with highly aggressive PCa features and adverse long-term oncological outcomes. This population is likely to benefit most from aggressive multimodal treatment. Nevertheless, we have shown for the first time that surgery remains a viable treatment option for patients with STAMPEDE high-risk PCa. PATIENT SUMMARY: Prostate cancer that meets the high-risk definitions from the STAMPEDE trial is an aggressive type of cancer. Our results for long-term cancer control outcomes indicate that surgery is a viable option for the subgroup of patients with this type of prostate cancer.

Fetal size monitoring in women with gestational diabetes and normal glucose tolerance.

AIMS: To monitor fetal size and identify predictors for birthweight in women with gestational diabetes (GDM) and normal glucose tolerance (NGT). METHODS: Cohort study of 1843 women universally screened for GDM, with routine ultrasounds each trimester. Women with GDM and NGT were categorized in subgroups by birthweight centile. RESULTS: Of the total cohort, 231 (12.5%) women were diagnosed with GDM. Fetal size, incidence of large-for-gestational age (LGA: 12.3% of GDM vs. 12.9% of NGT, p = 0.822) and small-for-gestational age (SGA) neonates (4.8% of GDM vs. 5.1% of NGT, p = 0.886) were similar between GDM and NGT. GDM women with LGA neonates were more insulin resistant at baseline and had more often estimated fetal weight (EFW) ≥ P90 on the 28-33 weeks ultrasound (p = 0.033) than those with AGA (appropriate-for-gestational age) neonates. Compared to NGT women with AGA neonates, those with LGA neonates were more often obese and multiparous, had higher fasting glycemia, a worse lipid profile, and higher insulin resistance between 24 -28 weeks, with more often excessive gestational weight gain. On the 28-33 weeks ultrasound, abdominal circumference ≥ P95 had a high positive predictive value for LGA neonates in GDM (100%), whereas, in both GDM and NGT, EFW ≥ P90 and ≤ P10 had a high negative predictive value for LGA and SGA neonates (> 88%), respectively. CONCLUSIONS: There were no differences in fetal size throughout pregnancy nor in LGA incidence between GDM and NGT women. EFW centile at 28-33 weeks correlated well with birthweight. This indicates that GDM treatment is effective and targeted ultrasound follow-up is useful. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT02036619. Registration date: January 15, 2014. https://clinicaltrials.gov/ct2/show/NCT02036619 .

One-year postpartum weight retention and glucose intolerance in women with prediabetes after gestational diabetes.

AIMS: To determine risk factors for 1-year postpartum weight retention (PPWR) and glucose intolerance (prediabetes + diabetes) in women with a previous history of gestational diabetes (GDM) and prediabetes in early postpartum. METHODS: In this exploratory analysis of the MELINDA randomized controlled trial, we report data of 167 women with prediabetes at the 6-16 weeks (early) postpartum oral glucose tolerance test after a recent history of GDM. RESULTS: Of all participants, 45% (75) had PPWR >0 kg at 1-year postpartum. Compared to women without PPWR, women with PPWR had higher gestational weight gain [10.5 ± 6.4 vs. 6.5 ± 4.5 kg, p < 0.001], higher BMI (p < 0.01) and a worse metabolic profile (higher waist circumference, worse lipid profile and more insulin resistance) (all p < 0.05) both in early and late postpartum. Of all women with PPWR, 40.0% developed metabolic syndrome, compared to 18.9% of women without late PPWR (p = 0.003). The only independent predictor for late PPWR was weight retention in early postpartum (p < 0.001). Of all participants, 55.1% (92) had glucose intolerance (84 prediabetes, 8 diabetes) 1-year postpartum. Independent predictors for late postpartum glucose intolerance were lower gestational age at start insulin therapy in pregnancy and delivery by caesarean section (resp. p = 0.044 and 0.014). CONCLUSIONS: In women with a previous history of GDM and prediabetes in early postpartum, PPWR in early postpartum was a strong independent predictor for late PPWR, while earlier start of insulin therapy during pregnancy and delivery by caesarean section were independent predictors of glucose intolerance in late postpartum.

Potentially actionable targets in synovial sarcoma: A tissue microarray study.

BACKGROUND: Synovial sarcoma (SynSa) is one of the most common translocation-related soft tissue sarcomas. Patients with metastatic SynSa have limited treatment options and a very poor prognosis. Several novel experimental therapies are currently being explored in clinical trials, including T cell-based therapies targeting cancer testis antigens such as New York esophageal squamous cell carcinoma 1 (NY-ESO-1) or melanoma-associated antigen A4 (MAGE-A4), and degraders targeting bromodomain-containing protein 9 (BRD9). Preclinical studies investigate inhibitors of Yes associated protein 1 (YAP1), transcriptional co-activator with PDZ-binding motif (TAZ) and inhibitors of chemokine receptor 4 (CXCR4). METHODS: We explored the immunohistochemical expression of these targets using a tissue microarray (TMA) constructed from 91 clinical SynSa samples and correlated these findings with corresponding clinicopathological data. RESULTS: Expression of MAGE-A4 and NY-ESO-1 was found in 69 % and 56 % of the samples, respectively. NY-ESO-1 was statistically higher expressed in samples from metastatic lesions as compared to samples from primary tumors. Nuclear expression of YAP1 and TAZ was observed in 92 % and 51 % of the samples, respectively. CXCR4 was expressed in the majority of the samples (82 %). BRD9 was highly expressed in all specimens. No prognostic role could be identified for any of the investigated proteins. CONCLUSION: This study is a comprehensive study providing real-world data on the expression of several actionable proteins in a large proportion of SynSa samples. All evaluated markers were expressed in a clinically meaningful proportion of cases represented in our TMA, supporting the relevance of ongoing preclinical and clinical research with novel agents directed against these targets.

Impact of breastfeeding on risk of glucose intolerance in early postpartum after gestational diabetes.

Aims: To determine the impact of breastfeeding on the risk of postpartum glucose intolerance in women with gestational diabetes. Methods: Sub-analysis of two multi-centric prospective cohort studies (BEDIP-N and MELINDA) in 1008 women with gestational diabetes. Data were collected during pregnancy and at a mean of 12 weeks postpartum. Multivariate logistic regression was used to estimate the effect of breastfeeding on glucose intolerance, with adjustment for ethnicity, education, income, professional activity and BMI. Results: Of all participants, 56.3% (567) breastfed exclusively, 10.1% (102) gave mixed milk feeding and 33.6% (339) did not breastfeed. Mean breastfeeding duration was 3.8 ± 2.4 and 3.7 ± 2.1 months in the breastfeeding and mixed milk feeding groups (p=0.496). The rate of glucose intolerance was lower in both the breastfeeding [22.3% (126)] and mixed milk feeding [25.5% (26)] groups compared to the no breastfeeding group [29.5% (100)], with an adjusted OR of 0.7 (95% CI 0.5-1.0) for glucose intolerance in the breastfeeding group compared to no breastfeeding group and an adjusted OR of 0.7 (95% CI 0.4-1.2) for the mixed milk feeding group compared to the no breastfeeding group. Postpartum, breastfeeding women had a lower BMI, less often postpartum weight retention, lower fasting triglycerides, less insulin resistance and a higher insulin secretion-sensitivity index-2 than the mixed milk feeding and no breastfeeding group. The mixed milk feeding group was more often from an non-White background, had a lower blood pressure and lower fasting triglycerides compared to the no breastfeeding group. Conclusions: Breastfeeding (exclusive and mixed milk feeding) is associated with less glucose intolerance and a better metabolic profile in early postpartum in women with gestational diabetes.

Clinical impact of using [18F]AlF-NOTA-octreotide PET/CT instead of [68Ga]Ga-DOTA-SSA PET/CT: Secondary endpoint analysis of a multicenter, prospective trial.

[18F]AlF-NOTA-octreotide ([18F]AlF-OC) is a promising alternative for [68Ga]Ga-DOTA-somatostatin analogs (SSAs) in positron emission tomography (PET) imaging of the somatostatin receptor (SSTR). Our aim is to assess changes in TNM staging and differences in patient management between [18F]AlF-OC PET/CT and [68Ga]Ga-DOTA-SSA PET/CT in the work-up of neuroendocrine tumor (NET) patients. Patients who underwent both [18F]AlF-OC and [68Ga]Ga-DOTA-TATE or [68Ga]Ga-DOTA-NOC PET/CT in our multicenter study (Pauwels et al., J Nucl Med.2023;63:632-638) with a NET were included for analysis. TNM staging was determined and compared for both tracers. For each patient, the blinded [68Ga]Ga-DOTA-SSA or [18F]AlF-OC PET/CT images were presented in random order at a multidisciplinary team board. The images were presented together with clinical information and compared with previous SSTR and [18F]FDG PET/CT imaging. After a consensus decision for patient management was recorded, the board was presented with the PET/CT images from the other SSTR tracer and a decision was made for the second tracer. Differences in management were classified as major if it entailed an intermodality change and minor if it led to an intramodality change. Compared with [68Ga]Ga-DOTA-SSA, the use of [18F]AlF-OC led to a change in 16/75 patients: TNM staging changes in 10/75 patients (13.3%; downstaging in 3/10, upstaging in 7/10) and differences in clinical management were seen in 10/75 patients (13.3%), leading to a major difference in 7/10 cases and a minor change in 3/10 cases. All 10 cases with a difference in patient management between both PET tracers were caused by additional lesion detection by [18F]AlF-OC. The use of [18F]AlF-OC did not impact TNM staging or clinical management in the large majority of the patients (86.7%), further validating the potential for routine clinical use of [18F]AlF-OC PET/CT as an alternative for [68Ga]Ga-DOTA-SSA PET/CT. The trial is registered under ClinicalTrials.gov identifier NCT04552847 and EudraCT 2020-000549-15.

Comparing advanced hybrid closed loop therapy and standard insulin therapy in pregnant women with type 1 diabetes (CRISTAL): a parallel-group, open-label, randomised controlled trial.

BACKGROUND: Advanced hybrid closed loop (AHCL) therapy can improve glycaemic control in pregnant women with type 1 diabetes. However, data are needed on the efficacy and safety of AHCL systems as these systems, such as the MiniMed 780G, are not currently approved for use in pregnant women. We aimed to investigate whether the MiniMed 780G can improve glycaemic control with less hypoglycaemia in pregnant women with type 1 diabetes. METHODS: CRISTAL was a double-arm, parallel-group, open-label, randomised controlled trial conducted in secondary and tertiary care specialist endocrinology centres at 12 hospitals (11 in Belgium and one in the Netherlands). Pregnant women aged 18-45 years with type 1 diabetes were randomly assigned (1:1) to AHCL therapy (MiniMed 780G) or standard insulin therapy (standard of care) at a median of 10·1 (IQR 8·6-11·6) weeks of gestation. Randomisation was done centrally with minimisation dependent on baseline HbA1c, insulin administration method, and centre. Participants and study teams were not masked to group allocation. The primary outcome was proportion of time spent in the pregnancy-specific target glucose range (3·5-7·8 mmol/L), measured by continuous glucose monitoring (CGM) at 14-17 weeks, 20-23 weeks, 26-29 weeks, and 33-36 weeks. Key secondary outcomes were overnight time in target range, and time below glucose range (<3·5 mmol/L) overall and overnight. Analyses were conducted on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT04520971). FINDINGS: Between Jan 15, 2021 and Sept 30, 2022, 101 participants were screened, and 95 were randomly assigned to AHCL therapy (n=46) or standard insulin therapy (n=49). 43 patients assigned to AHCL therapy and 46 assigned to standard insulin therapy completed the study. At baseline, 91 (95·8%) participants used insulin pumps, and the mean HbA1c was 6·5% (SD 0·6). The mean proportion of time spent in the target range (averaged over four time periods) was 66·5% (SD 10·0) in the AHCL therapy group compared with 63·2% (12·4) in the standard insulin therapy group (adjusted mean difference 1·88 percentage points [95% CI -0·82 to 4·58], p=0·17). Overnight time in the target range was higher (adjusted mean difference 6·58 percentage points [95% CI 2·31 to 10·85], p=0·0026), and time below range overall (adjusted mean difference -1·34 percentage points [95% CI, -2·19 to -0·49], p=0·0020) and overnight (adjusted mean difference -1·86 percentage points [95% CI -2·90 to -0·81], p=0·0005) were lower with AHCL therapy than with standard insulin therapy. Participants assigned to AHCL therapy reported higher treatment satisfaction. No unanticipated safety events occurred with AHCL therapy. INTERPRETATION: In pregnant women starting with tighter glycaemic control, AHCL therapy did not improve overall time in target range but improved overnight time in target range, reduced time below range, and improved treatment satisfaction. These data suggest that the MiniMed 780G can be safely used in pregnancy and provides some additional benefits compared with standard insulin therapy; however, it will be important to refine the algorithm to better align with pregnancy requirements. FUNDING: Diabetes Liga Research Fund and Medtronic.

Intra/inter-observer reliability of cystoscopic sphincter evaluation in men undergoing sling surgery.

OBJECTIVES: To assess the intra/inter-observer reliability of cystoscopic sphincter evaluation (CSE) in men undergoing sling surgery for urinary incontinence and if possible to evaluate its correlation with the final clinical decision. PATIENTS AND METHODS: Two expert urologists prospectively filmed and recorded, incontinent patient's cystoscopies according to a standard scenario. Anonymised recordings where randomly offered to the same observer twice. The observers (medical students, urology residents and full urologist with 0-5, 5-10, >10 years of practice, respectively) were asked to assess and score the recordings without knowing any of the patients' characteristics. RESULTS: In total, 37 recordings were scored twice by the 26 observers. The intraclass correlation coefficient (ICC) for intra-observer reliability of the CSE was 0.54 (moderate), 0.58 (moderate) and 0.60 (substantial) for medical students, residents, and urologists, respectively. However, when stratifying observers according to their experience, the lowest agreement values were found between experts with >10 years of experience. The inter-observer reliability for the CSE ICCs ranged between 0.31and 0.53, with the lowest ICC value observed between urologists (0.31). CONCLUSIONS: The study demonstrates poor intra- and inter-observer reliability of the CSE. According to these results, a CSE does not add valuable information to the clinical evaluation. In this scenario, it should not be considered in isolation from the patient's characteristics.

VaNoLaH trial: a study protocol-a multinational randomised controlled trial including two identical substudies comparing vaginal versus vNOTES (vaginal natural orifice transluminal surgery) hysterectomy or laparoscopic versus vNOTES hysterectomy.

INTRODUCTION: Hysterectomy is one of the most common surgeries performed in women. Minimally invasive methods are on the rise globally as they have been shown to decrease surgical morbidity compared with abdominal hysterectomy. Hysterectomy by vaginal natural orifice transluminal endoscopic surgery (vNOTES) is the latest innovation. It combines the vaginal approach and endoscopy via the vagina. Large pragmatic randomised controlled trials (RCTs) are lacking comparing outcomes after vNOTES, vaginal hysterectomy (VH) and laparoscopic hysterectomy (LH). METHODS: Multicentre pragmatic RCT aiming to recruit 1000 women aged 18-75 years undergoing hysterectomy for benign disease. The RCT includes two identical substudies (groups A and B). If VH is considered safe and feasible, the patient will be randomised within group A (VH vs vNOTES). If VH is not considered safe or feasible, patients will be randomised within group B (LH vs vNOTES). ANALYSIS: Primary outcome is the proportion of women leaving the hospital within 12 hours after surgery. Secondary outcomes are hospitalisation time, conversion rates, duration of the surgical procedure, intraoperative complications, postoperative complications and readmission. ETHICS AND DISSEMINATION: The Ethical Board Committee at Imelda Hospital, Bonheiden, Belgium, has approved the research protocol 230704 (principal investigator). Before including patients, all centres will require local or national ethical approval. The results of the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05971875.

Pharmacovigilance of nephrotoxic drugs in neonates: the Pottel method for acute kidney injury detection in ELBW neonates.

BACKGROUND: Extremely low birth weight (ELBW) neonates (birth weight ≤ 1000 g) are at high risk to develop drug-induced acute kidney injury (AKI). However, we lack a pragmatic detection tool to capture their time-dependent (patho)physiologic serum creatinine (Scr) patterns. Pottel et al. suggested rescaling Scr by dividing Scr with the mean Scr value of the age- and sex-specific reference population. We explored if this Pottel method can detect drug-related nephrotoxicity in ELBW neonates. METHODS: A previously reported dataset on Scr changes in ELBW neonates exposed to ibuprofen, amikacin, or vancomycin was updated to calculate Pottel scores for every available Scr value in the first 28 postnatal days. We hereby used previously published postnatal age-specific 50th centile values in an ELBW population. Linear mixed models were applied, analyzing Pottel scores as response variable and continuous time (day), drug exposure, and interaction thereof in the explanatory model. RESULTS: Serum creatinine (n = 3231) observations in 201 ELBW neonates were collected. A statistically significant rise of Pottel scores was observed with ibuprofen starting from postnatal day 4. In addition, a cumulative effect of treatment with mean Pottel scores on day 0 of 1.020 and on day 3 during treatment of 1.106 (95% CI 1.068-1.145, p < 0.001) was observed, corrected for effect of antibiotics. Antibiotic administrations showed a small but statistically significant difference up to postnatal day 5. CONCLUSIONS: As rescaled Scr biomarker, the Pottel method showed a clear association with ibuprofen-exposed ELBW neonates, suggesting its applicability as a pragmatic bedside alternative tool to assess nephrotoxicity.

Effectiveness of a blended mobile-based lifestyle intervention in women with glucose intolerance after a recent history of gestational diabetes (MELINDA): a 1-year, prospective, multicentre, randomised controlled trial.

Background: Women with glucose intolerance after gestational diabetes mellitus (GDM) are at high risk to develop type 2 diabetes. Traditional lifestyle interventions in early postpartum have limited impact. We investigated the efficacy of a blended mobile-based lifestyle intervention in women with glucose intolerance after a recent history of GDM. Methods: Prospective, double-arm, non-masked, multicentre randomised controlled trial (RCT) in which women with glucose intolerance, diagnosed 6-16 weeks after a GDM-complicated pregnancy, were assigned 1:1 to a one-year blended-care, telephone- and mobile-based lifestyle program (intervention) or usual care (control). Primary endpoint was the proportion of women able to achieve their weight goal (≥5% weight loss if prepregnancy BMI ≥ 25 kg/m2 or return to prepregnancy weight if prepregnancy BMI < 25 kg/m2) in the intention-to-treat sample. Key secondary outcomes were frequency of glucose intolerance, diabetes and metabolic syndrome, and lifestyle-related outcomes assessed with self-administered questionnaires. The study was registered in ClinicalTrials.gov (NCT03559621). Findings: Between April 10th 2019 and May 13th 2022, 240 participants were assigned to the intervention (n = 121) or control group (n = 119), of which 167 (n = 82 in intervention and n = 85 in control group) completed the study. Primary outcome was achieved by 46.3% (56) of intervention participants compared to 43.3% (52) in the control group [odds ratio (OR) 1.13, 95% confidence interval (CI) 0.63-2.03, p = 0.680; risk ratio 1.07, 95% CI (0.78-1.48)]. Women in the intervention group developed significantly less often metabolic syndrome compared to the control group [7.3% (6) vs. 16.5% (14), OR 0.40, CI (0.22-0.72), p = 0.002], reported less sedentary behaviour and higher motivation for continuing healthy behaviours. In the intervention group, 84.1% (69) attended at least eight telephone sessions and 70.7% (58) used the app at least once weekly. Interpretation: A blended, mobile-based lifestyle intervention was not effective in achieving weight goals, but reduced the risk to develop metabolic syndrome. Funding: Research fund of University Hospitals Leuven, Novo Nordisk, Sanofi, AstraZeneca, Boehringer-Ingelheim, Lilly.

The prognostic effect of radiological extranodal extension in HPV-positive oropharyngeal squamous cell carcinomas: a retrospective cohort analysis.

PURPOSE: Radiological extranodal extension (rENE) is a well-known negative prognosticator in head and neck squamous cell carcinoma (HNSCC). However, controversy remains regarding the prognostic effect of rENE in HPV-positive oropharyngeal SCCs (OPSCC). This single-center retrospective cohort analysis assessed the prognostic role of rENE in an HPV + OPSCC population and tried to validate a recently proposed modification of the TNM8 N-classification. METHODS: 129 patients with HPV + OPSCC, of whom 106 cN + patients, were included. Radiological imaging (CT, MRI or both) was reanalyzed by a senior head and neck radiologist. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRFS), and disease-specific survival (DSS) were evaluated. Cox proportional hazard models were used for estimating hazard ratios (HR). RESULTS: A non-significant trend towards better outcomes in the rENE- group, as compared to the rENE + population, was observed for 5 year OS [80.99% vs 68.70%, HR: 2.05, p = 0.160], 5 year RFS [78.81% vs 67.87%, HR: 1.91, p = 0.165], 5 year DFS [77.06% vs 60.16%, HR: 2.12, p = 0.0824] and 5 year DSS [88.83% vs 81.93%, HR: 2.09, p = 0.195]. OS declined with ascending levels of rENE (p = 0.020). Multivariate analysis identified cT-classification and smoking as independent negative predictors for OS/DFS. The proposed modification of the TNM8 N-classification could not be validated. CONCLUSIONS: Although rENE could not be identified as an independent negative prognosticator for outcome in our HPV + OPSCC population, outcomes tend to deteriorate with increasing rENE.

Prospective Evaluation and Validation of the Laryngoscore and the mini-Laryngoscore.

OBJECTIVE: The Laryngoscore was described in 2014 as a practical preoperative assessment tool to predict difficult laryngeal exposure (DLE) during transoral approaches to the larynx. In 2019 the authors proposed a version with a reduced number of variables, called the mini-Laryngoscore. We aim to critically appraise and externally validate these two tools and if needed and possible, to optimize these tools. METHODS: 103 consecutive patients who underwent a microlaryngoscopy between November 2017 and June 2020 at the Leuven University Hospitals were prospectively included and subjected to a presurgical evaluation of 15 parameters and a peroperative scoring of the anterior commissure visualization. Subsequent analysis focused on the concordance of our findings with those of Piazza et al., the discriminatory ability of the test, and the validity of the included items. We then evaluated a modified prediction tool. RESULTS: Of 103 patients, 18 (17.5%) had DLE. The Laryngoscore and mini-Laryngoscore predicted this with a "good" C-index of respectively 0.727 (95%CI: 0.608-0.846) and 0.714 (95%CI: 0.605-0.823). A newly created prediction tool including only three parameters (Interincisors gap, upper jaw dental status and previous treatments) showed a better discriminatory ability (C-index = 0.835, 95%CI: 0.726-0.944) than the original Laryngoscore, a finding that needs further external validation. CONCLUSION: The original Laryngoscore and the mini-Laryngoscore displayed a good discriminative ability. Some parameters can be left out of the Laryngoscore without losing discrimination. An even better prediction model seems possible, using a weighted sum of selected predictor variables and by using the parameters in their continuous form. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:1807-1812, 2024.

Intra-individual qualitative and quantitative comparison of [68Ga]Ga-DOTATATE PET/CT and PET/MRI.

Background: Somatostatin receptor (SSTR) positron emission tomography (PET) is a cornerstone of neuroendocrine tumor (NET) management. Hybrid PET/magnetic resonance imaging (MRI) is now available for NET-imaging, next to PET/computed tomography (CT). Objectives: To determine whether CT or MRI is the best hybrid partner for [68Ga]Ga-DOTATATE PET. Design: Monocentric, prospective study. Methods: Patients received a same-day [68Ga]Ga-DOTATATE PET/CT and subsequent PET/MRI, for suspicion of NET, (re)staging or peptide receptor radionuclide therapy-selection. The union (PETunion) of malignant lesions detected on PETCT and PETMRI was the reference standard. Concordance of detection of malignant lesions in an organ was measured between PETunion and CT and PETunion and MRI. Seven bins were used to categorize the number of malignant lesions, containing following ordinal variables: 0, 1, 2-5, 6-10, 11-20, >20 countable and diffuse/uncountable. The difference in number of malignant lesions was obtained as the difference in bin level ('Δbin') between PETunion and CT and PETunion and MRI with a Δbin closer to zero implying a higher concordance rate. Results: Twenty-nine patients were included. Primary tumors included 17 gastroenteropancreatic-NETs, 1 colon neuroendocrine carcinoma, 7 lung-NETs and 2 meningiomas. Patient level concordance with PETunion was 96% for MRI and 67% for CT (p = 0.039). Organ level concordance with PETunion was 74% for MRI and 40% for CT (p < 0.0001). In bone, there was a higher concordance rate for MRI compared to CT, 92% and 33%, respectively (p = 0.016). Overall, a mean Δbin of 0.5 ± 1.1 for PETunion/MRI and 1.4 ± 1.2 for PETunion/CT (p < 0.0001) was noted. In liver, a mean Δbin of 0.0 ± 1.1 for PETunion/MRI and 1.7 ± 1.2 for PETunion/CT was observed (p = 0.0078). In bone, a mean Δbin closer to zero was observed for PETunion/MRI compared to PETunion/CT, 0.6 ± 1.4 and 2.0 ± 1.5, respectively (p = 0.0098). Conclusions: Compared to SSTR PET/CT, SSTR PET/MRI had a higher patient and organ level concordance for malignant tumoral involvement and number of malignant lesions, with a clear added value in bone and liver specifically.

Circulating biomarkers at diagnosis correlate with distant metastases of early luminal-like breast cancer.

There is an urgent need for new and better biomarker modalities to estimate the risk of recurrence within the luminal-like breast cancer (BC) population. Molecular diagnostic tests used in the clinic lack accuracy in identifying patients with early luminal BC who are likely to develop metastases. This study provides proof of concept that various liquid biopsy read-outs could serve as valuable candidates to build a multi-modal biomarker model distinguishing, already at diagnosis, between early metastasizing and non-metastasizing patients. All these blood biomarkers (chemokines, microRNAs, leukemia inhibitory factor, osteopontin, and serum-induced functional myeloid signaling responses) can be measured in baseline plasma/serum samples and could be added to the existing prognostic factors to improve risk stratification and more patient-tailored treatment in early luminal BC.

Immediate and 90-Day Clinical Outcome of Patients with Acute Stroke Treated with the NeVa-Vesalio Mechanical Thrombectomy Device: A Retrospective Case Series.

OBJECTIVE: The NeVa stent retriever is a newly designed mechanical thrombectomy device for the treatment of acute ischemic stroke caused by large vessel occlusion. We investigate the procedural characteristics and patients' clinical outcomes at discharge and at 90 days of follow-up. METHODS: We retrospectively reviewed a cohort of 75 patients (median age, 74 years) treated with the NeVa device for acute large vessel occlusion stroke. Per pass modified Treatment in Cerebral Infarction (mTICI) scores, procedural complications, and clinical outcome parameters including the National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale (mRS) score, and mortality were analyzed, based on patients' electronic medical records. RESULTS: Complete first pass effect was observed in 24 patients (32%). Vasospasm, repeated re-thrombosis, failure to advance the NeVa device through the microcatheter, and symptomatic intracranial hemorrhage were observed in 2, 1, 1, and 2 patient(s) respectively. The rate of complete (mTICI 2c-3) reperfusion was achieved in 61 patients (81.33%), with a median number of 2 passes (1-3). Median NIHSS score on admission, after 24 hours, and after 5-10 days or at discharge was 19 (15-23), 11 (4-19), and 3 (2-13.5), respectively. The number of patients with a functional mRS score (0-2) at 90 days follow-up was 29 (39%). CONCLUSIONS: Endovascular stroke management with use of the NeVa-Vesalio stent retriever may be associated with a 90-day functional mRS score in nearly 40% of treated patients.