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.

The QTc-Bazett Interval in Former Very Preterm Infants in Adolescence and Young Adulthood is Not Different from Term-Born Controls.

INTRODUCTION: Although relevant for precision pharmacovigilance, there are conflicting data on whether former preterm birth is associated with QTc-Bazett prolongation in later life. METHODS: To explore QTc-Bazett interval differences between former preterm and/or extremely low birth weight (ELBW) cases and term-born controls in adolescence and young adulthood, we analyzed pooled individual data after a structured search on published cohorts. To test the absence of a QTc-Bazett difference, a non-inferiority approach was applied (one-sided, upper limit of the 95% confidence interval [CI] mean QTc-Bazett difference, 5 and 10 ms). We also investigated the impact of characteristics, either perinatal or at assessment, on QTc-Bazett in the full dataset (cases and controls). Data were reported as median and range. RESULTS: The pooled dataset contained 164 former preterm and/or ELBW (cases) and 140 controls born full-term from three studies. The median QTc-Bazett intervals were 409 (335-490) and 410 (318-480) ms in cases and controls. The mean QTc-Bazett difference was 1 ms, with an upper 95% CI of 6 ms (p > 0.05 and p < 0.01 for 5 and 10 ms, respectively). In the full dataset, females had a significantly longer QTc-Bazett than males (415 vs. 401 ms; p < 0.0001). CONCLUSIONS: QTc-Bazett intervals are not significantly different between former preterm and/or ELBW cases and term-born controls, and we rejected a potential prolongation > 10 ms in cases. When prescribing QTc-prolonging drugs, pharmacovigilance practices in this subpopulation should be similar to the general public (NCT05243537).

Factors influencing outcome of angiographic embolization for gastroduodenal hemorrhage related to peptic ulceration.

PURPOSE: Long-term outcome and prognostic factors of transcatheter embolization for gastroduodenal peptic ulcer bleeding are unknown. This study was conducted to evaluate the clinical outcome and factors associated with early recurrent bleeding and 30-day mortality of transcatheter arterial embolization (TAE) for severe, upper gastroduodenal hemorrhage associated with peptic ulcer and refractory to medical and endoscopic therapy. METHODS: A monocenter, retrospective study from 2005 to 2020 including 76 consecutive patients who underwent TAE as first-line therapy for bleeding gastroduodenal peptic ulcers refractory to endoscopic therapy. Patient demographics, endoscopy findings, co-morbidities and interventional procedure findings were recorded. The outcome measures were technical and clinical success, procedure related complications, recurrent bleeding, length of hospital stay, 30-day mortality and overall survival. RESULTS: The technical success rate was 96% and the clinical success rate was 65,8%. The rebleeding and 30-day mortality rate were 30,7% and 22,4% respectively. A higher international normalized ratio (INR) was a statistically significant risk factor for 30-day mortality (OR, 7.15; 95% CI, 1.67-30.70; p = 0.008). The mean overall survival was 3.76 years (1.16---5.09; 95% CI); a lower Charlson Comorbidity Index (CCI) and a lower Rockall score were significantly associated with a longer overall survival (HR, 1.24; 95% CI, 1.14-1.35; p = 0.0001; HR, 1.32; 95% CI, 1.10-1.59; p = 0.003) respectively. Early rebleeding was significantly associated with a lower overall survival (HR, 2.72; 95% CI, 1.57-4.71; p = 0.0004). CONCLUSION: A higher INR was a significant risk factor with a higher 30-day mortality. A lower CCI, a lower Rockall score and the absence of early rebleeding were significantly associated with a longer overall survival.

Prospective comparison of [18F]AlF-NOTA-octreotide PET/MRI to [68Ga]Ga-DOTATATE PET/CT in neuroendocrine tumor patients.

BACKGROUND: Fluorine-18-labeled SSAs have the potential to become the next-generation tracer in SSTR-imaging in neuroendocrine tumor (NET) patients given their logistical advantages over the current gold standard gallium-68-labeled SSAs. In particular, [18F]AlF-OC has already shown excellent clinical performance. We demonstrated in our previous report from our prospective multicenter trial that [18F]AlF-OC PET/CT outperforms [68Ga]Ga-DOTA-SSA, but histological confirmation was lacking due to ethical and practical reasons. In this second arm, we therefore aimed to provide evidence that the vast majority of [18F]AlF-OC PET lesions are in fact true NET lesions by analyzing their MR characteristics on simultaneously acquired MRI. We had a special interest in lesions solely detected by [18F]AlF-OC ("incremental lesions"). METHODS: Ten patients with a histologically confirmed neuroendocrine tumor (NET) and a standard-of-care [68Ga]Ga-DOTATATE PET/CT, performed within 3 months, were prospectively included. Patients underwent a whole-body PET/MRI (TOF, 3 T, GE Signa), 2 hours after IV injection of 4 MBq/kg [18F]AlF-OC. Positive PET lesions were evaluated for a corresponding lesion on MRI. The diagnostic performance of both PET tracers was evaluated by determining the detection ratio (DR) for each scan and the differential detection ratio (DDR) per patient. RESULTS: In total, 195 unique lesions were detected: 167 with [68Ga]Ga-DOTATATE and 193 with [18F]AlF-OC. The DR for [18F]AlF-OC was 99.1% versus 91.4% for [68Ga]Ga-DOTATATE, significant for non-inferiority testing (p = 0.0001). Out of these 193 [18F]AlF-OC lesions, 96.2% were confirmed by MRI to be NET lesions. Thirty-three incremental lesions were identified by [18F]AlF-OC, of which 91% were confirmed by MRI and considered true positives. CONCLUSION: The DR of [18F]AlF-OC was numerically higher and non-inferior to the DR of [68Ga]Ga-DOTATATE. [18F]AlF-OC lesions and especially incremental lesions were confirmed as true positives by MRI in more than 90% of lesions. Taken together, these data further validate [18F]AlF-OC as a new alternative for SSTR PET in clinical practice. Trial registration ClinicalTrials.gov: NCT04552847. Registered 17 September 2020, https://beta. CLINICALTRIALS: gov/study/NCT04552847.

Normal glucose tolerant women with low glycemia during the oral glucose tolerance test have a higher risk to deliver a low birth weight infant.

Background: Data are limited on pregnancy outcomes of normal glucose tolerant (NGT) women with a low glycemic value measured during the 75g oral glucose tolerance test (OGTT). Our aim was to evaluate maternal characteristics and pregnancy outcomes of NGT women with low glycemia measured at fasting, 1-hour or 2-hour OGTT. Methods: The Belgian Diabetes in Pregnancy-N study was a multicentric prospective cohort study with 1841 pregnant women receiving an OGTT to screen for gestational diabetes (GDM). We compared the characteristics and pregnancy outcomes in NGT women according to different groups [(<3.9mmol/L), (3.9-4.2mmol/L), (4.25-4.4mmol/L) and (>4.4mmol/L)] of lowest glycemia measured during the OGTT. Pregnancy outcomes were adjusted for confounding factors such as body mass index (BMI) and gestational weight gain. Results: Of all NGT women, 10.7% (172) had low glycemia (<3.9 mmol/L) during the OGTT. Women in the lowest glycemic group (<3.9mmol/L) during the OGTT had compared to women in highest glycemic group (>4.4mmol/L, 29.9%, n=482), a better metabolic profile with a lower BMI, less insulin resistance and better beta-cell function. However, women in the lowest glycemic group had more often inadequate gestational weight gain [51.1% (67) vs. 29.5% (123); p<0.001]. Compared to the highest glycemia group, women in the lowest group had more often a birth weight <2.5Kg [adjusted OR 3.41, 95% CI (1.17-9.92); p=0.025]. Conclusion: Women with a glycemic value <3.9 mmol/L during the OGTT have a higher risk for a neonate with birth weight < 2.5Kg, which remained significant after adjustment for BMI and gestational weight gain.

Comparison of Clinical Performance Between Two Types of Symmetric-Tip Hemodialysis Catheters: A Single-Centre, Randomized Trial.

PURPOSE: To compare the clinical performance of a newly designed, symmetric-tip Arrow-Clark™ VectorFlow® tunnelled haemodialysis catheter, with a Glidepath™, symmetric-tip tunnelled haemodialysis catheter. MATERIAL AND METHODS: From November 2018 to October 2020, patients with End-Stage Renal Disease requiring a de novo tunnelled catheter for hemodialysis, were randomized to Vectorflow® (n = 50) or to Glidepath™ catheter (n = 48). The primary outcome was catheter patency at one year following catheter insertion. Catheter failure was defined as the removal of the catheter due to infectious complications, or low blood flow rate by intraluminal thrombosis or fibrin sheath occlusion. Secondary outcomes were blood flow rate, fractional urea clearance and urea reduction ratio during dialysis. RESULTS: Demographic characteristics were not different between the two groups. At three months and on the one-year endpoint the patency rates with the Vectorflow® catheter were 95.83% and 83.33% respectively, compared to 93.02% at both endpoints with the Glidepath™ catheter (P = 0.27). Catheter failure to infectious complications or low blood flow rate was similar in both groups. Catheter blood flow rate reached the threshold of 300 ml/min at all time points for both catheters. All patients had a high mean fractional urea clearance (1.6-1.7). CONCLUSIONS: The catheter patency rate was not significantly different in patients with a VectorFlow® or a Glidepath™ catheter. Both catheters presented satisfactory dialysis adequacy over one year.

Role of immune checkpoint inhibitors in metastatic uveal melanoma: a single-center retrospective cohort study.

BACKGROUND: Uveal melanoma is an orphan malignancy with very limited data on treatment options in metastatic setting. METHODS: In this single-center retrospective study, we describe real-world epidemiological and survival data on 121 metastatic uveal melanoma (MUM) patients registered in our institution. As a large tertiary referral center, almost 30% of all diagnoses in the Flemish region of Belgium were covered. Primarily, we determined whether introduction of immune checkpoint inhibitors (ICI) led to improved overall survival (OS) in MUM patients. Secondarily, response rates to ICI were assessed and we evaluated whether first-line ICI could be a valid alternative to liver-directed therapy (LDT) in liver-only disease. RESULTS: The initially perceived 10.8 months survival benefit from treatment with ICI disappeared after correction for immortality bias. By analyzing treatment type as time-varying covariate on OS, no significant benefit of ICI over other systemic therapies (HR = 0.771) or best supportive care (BSC) (HR = 0.780) was found. Also comparison of the pre-ICI versus ICI era showed no OS improvement after introduction of ICI in our center (p = 0.7994). Only liver-directed and local oligometastatic approaches were associated with a lower chance of mortality when compared to ICI (p = 0.0025), other systemic therapies (p = 0.0001) and BSC (p = 0.0003), yet without correction for selection bias. We reported overall response rates on ICI ranging from 8-15% and we found some support for neoadjuvant strategies with ICI resulting in remission or downsizing, allowing oligometastatic approaches later on. In first-line liver-only disease, median real-world progression-free survival and OS did not significantly differ between patients treated with LDT or ICI upfront (p = 0.2930 and p = 0.5461 respectively). CONCLUSION: Although we documented responses to ICI, our analyses do not demonstrate an OS benefit of ICI over alternative treatment strategies for MUM. However, local treatment options, whether liver-directed or for oligometastatic disease, may be beneficial and should be considered.

Weight retention and glucose intolerance in early postpartum after gestational diabetes.

OBJECTIVES: To determine risk factors for early postpartum weight retention (PPWR) and glucose intolerance (GI) in women with gestational diabetes (GDM). DESIGN & METHODS: Prospective, multicenter (n=8) cohort study in 1201 women with a recent history of GDM. Pregnancy and postpartum characteristics, and data from self-administered questionnaires were collected at the 6-16 weeks postpartum 75g OGTT. RESULTS: Of all participants, 38.6% (463) had moderate (>0 and ≤5 kg) and 15.6% (187) had high (>5kg) PPWR. Independent predictors for early PPWR were excessive gestational weight gain (GWG), lack of breastfeeding, higher dietary fat intake, insulin use during pregnancy, multiparity, lower prepregnancy BMI, and lower education degree. Compared to PPWR <5 kg, women with high PPWR had a more impaired postpartum metabolic profile, breastfed less often, had higher depression rates [23.1% (43) vs. 16.0% (74), p=0.035] and anxiety levels, and lower quality of life. Of all participants, 28.0% (336) had GI [26.1% (313) prediabetes and 1.9% (23) diabetes]. Women with high PPWR had more often GI compared to women without PPWR [33.7% (63) vs. 24.9% (137), p=0.020]. Only 12.9% (24) of women with high PPWR perceived themselves at high risk for diabetes but they were more often willing to change their lifestyle than women with moderate PPWR. CONCLUSIONS: Modifiable risk factors such as lifestyle, prepregnancy BMI, GWG, and mental health can be used to identify a subgroup of women with GDM at the highest risk of developing early PPWR, allowing for a more personalized follow-up.

Coronary covered stents in the management of late-onset arterial complications post-hepato-pancreato-biliary surgery.

PURPOSE: To retrospectively evaluate the safety, efficacy, and late clinical outcome of coronary covered stent placement for the treatment of late-onset arterial complications after hepato-pancreato-biliary surgery. MATERIALS AND METHODS: Consecutive patients presenting with post-hepato-pancreato-biliary surgery-related arterial lesions and subsequently treated with a covered coronary stent in the authors institution between January 2012 and November 2021 were included. Primary endpoints were technical and clinical success; secondary endpoints were covered stent patency and end-organ perfusion of the affected artery. RESULTS: The study included 22 patients (13 men and 9 women) with a mean age of 67 years ± 9.6 years. Initial surgery included pancreaticoduodenectomy (n = 15; 68%), liver transplantation (n = 2; 9%), left hepatectomy (n = 1; 5%), bile duct resection (n = 1; 5%), hepatogastrostomy (n = 1; 5%), and segmental enterectomy (n = 1; 5%). Technically, coronary covered stents were successfully placed in n = 22 patients (100%) without immediate complication. Definitive bleeding control was observed in n = 18 patients (81.1%) with recurrent bleeding within 30 days postintervention in n = 5 patients (23%). No ischemic liver or biliary complications occurred during the follow-up period. The 30-day mortality rate was 0%. CONCLUSION: Coronary covered stents are a safe and efficient treatment option in most of the patients presenting with late-onset postoperative arterial injuries following hepato-pancreato-biliary surgery and are associated with an acceptable recurrent bleeding rate and no late, ischemic, parenchymal complications.