New insights along the gut-liver axis in cardiometabolic disease

In this thesis we targeted the human gut microbiome for the development of therapeutic strategies in metabolic disorders. In chapter 3 we performed a randomized placebo-controlled cross-over study in individuals with the metabolic syndrome in which we showed that a single duodenal infusion of A. soehngenii improved peripheral glycemic control. In chapter 4 we studied the effect of a 2 weeks oral A. soehngenii treatment in individuals with T2D treated with metformin on their glycemic control.The second part of the thesis focused on MASLD, currently the most common cause of chronic liver dysfunction worldwide. In chapter 5 we reviewed the gut microbial and gut microbial-derived metabolite signatures associated with the development and disease progression of MASLD. To dissect causality of intestinal microbiota in MASLD, in chapter 6 we performed a single-center, double-blind, randomized controlled proof-of-principle pilot study comparing the effect of three 8-weekly lean vegan donor FMT versus autologous FMT on the severity of MASLD, using liver biopsies in individuals with hepatic steatosis on ultrasound. Moreover, we aimed to identify and validate noninvasive diagnostic methods in disease progression in MASLD. Hence, in chapter 7 we examined the diagnostic performance of multiparametric MRI for the assessment of disease severity along the MASLD disease spectrum with comparison to histological scores

Quality indicators for bladder cancer services : a collaborative review

Context There is a lack of accepted consensus on what should constitute appropriate quality-of-care indicators for bladder cancer. Objective To evaluate the optimal management of bladder cancer and propose quality indicators (QIs). Evidence acquisition A systematic review was performed to identify literature on current optimal management and potential quality indicators for both non–muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer. A panel of experts was convened to select a recommended list of QIs. Evidence synthesis For NMIBC, preoperative QIs include tobacco cessation counselling and appropriate imaging before initial transurethral resection of bladder tumour (TURBT). Intraoperative QIs include administration of antibiotics, proper safe conduct of TURBT using a checklist, and performing restaging TURBT with biopsy of the prostatic urethra in appropriate cases. Postoperative QIs include appropriate receipt of perioperative adjuvant therapy, risk-stratified surveillance, and appropriate decision to change therapy when indicated (eg, unresponsive to bacillus Calmette-Guerin). For MIBC, preoperative QIs include multidisciplinary care, selection for candidates for continent urinary diversion, receipt of neoadjuvant cisplatin-based chemotherapy, time to commencing radical treatment, consideration of trimodal therapy as a bladder-sparing alternative in select patients, preoperative counselling with stoma marking, surgical volume of radical cystectomy, and enhanced recovery after surgery protocols. Intraoperative QIs include adequacy of lymphadenectomy, blood loss, and operative time. Postoperative QIs include prospective standardised monitoring of morbidity and mortality, negative surgical margins for pT2 disease, appropriate surveillance after primary treatment, and adjuvant cisplatin-based chemotherapy in appropriate cases. Participation in clinical trials was highlighted as an important component indicating high quality of care. Conclusions We propose a set of QIs for both NMIBC and MIBC based on established clinical guidelines and the available literature. Measurement of these QIs could aid in improvement and benchmarking of optimal care of bladder cancer. Patient summary After a systematic review of existing guidelines and literature, a panel of experts has recommended a set of quality indicators that can help providers and patients measure and strive towards optimal outcomes for bladder cancer care

Diagnostic yield and accuracy of CT angiography, MR angiography, and digital subtraction angiography for detection of macrovascular causes of intracerebral haemorrhage: Prospective, multicentre cohort study

Study question What are the diagnostic yield and accuracy of early computed tomography (CT) angiography followed by magnetic resonance imaging/angiography (MRI/MRA) and digital subtraction angiography (DSA) in patients with non-traumatic intracerebral haemorrhage? Methods This prospective diagnostic study enrolled 298 adults (18-70 years) treated in 22 hospitals in the Netherlands over six years. CT angiography was performed within seven days of haemorrhage. If the result was negative, MRI/MRA was performed four to eight weeks later. DSA was performed when the CT angiography or MRI/MRA results were inconclusive or negative. The main outcome was a macrovascular cause, including arteriovenous malformation, aneurysm, dural arteriovenous fistula, and cavernoma. Three blinded neuroradiologists independently evaluated the images for macrovascular causes of haemorrhage. The reference standard was the best available evidence from all findings during one year's follow-up. Study answer and limitations A macrovascular cause was identified in 69 patients (23%). 291 patients (98%) underwent CT angiography; 214 with a negative result underwent additional MRI/MRA and 97 with a negative result for both CT angiography and MRI/MRA underwent DSA. Early CT angiography detected 51 macrovascular causes (yield 17%, 95% confidence interval 13% to 22%). CT angiography with MRI/MRA identified two additional macrovascular causes (18%, 14% to 23%) and these modalities combined with DSA another 15 (23%, 18% to 28%). This last extensive strategy failed to detect a cavernoma, which was identified on MRI during follow-up (reference strategy). The positive predictive value of CT angiography was 72% (60% to 82%), of additional MRI/MRA was 35% (14% to 62%), and of additional DSA was 100% (75% to 100%). None of the patients experienced complications with CT angiography or MRI/MRA; 0.6% of patients who underwent DSA experienced p

New insights along the gut-liver axis in cardiometabolic disease

In this thesis we targeted the human gut microbiome for the development of therapeutic strategies in metabolic disorders. In chapter 3 we performed a randomized placebo-controlled cross-over study in individuals with the metabolic syndrome in which we showed that a single duodenal infusion of A. soehngenii improved peripheral glycemic control. In chapter 4 we studied the effect of a 2 weeks oral A. soehngenii treatment in individuals with T2D treated with metformin on their glycemic control.The second part of the thesis focused on MASLD, currently the most common cause of chronic liver dysfunction worldwide. In chapter 5 we reviewed the gut microbial and gut microbial-derived metabolite signatures associated with the development and disease progression of MASLD. To dissect causality of intestinal microbiota in MASLD, in chapter 6 we performed a single-center, double-blind, randomized controlled proof-of-principle pilot study comparing the effect of three 8-weekly lean vegan donor FMT versus autologous FMT on the severity of MASLD, using liver biopsies in individuals with hepatic steatosis on ultrasound. Moreover, we aimed to identify and validate noninvasive diagnostic methods in disease progression in MASLD. Hence, in chapter 7 we examined the diagnostic performance of multiparametric MRI for the assessment of disease severity along the MASLD disease spectrum with comparison to histological scores

MRI-guided focal laser ablation for prostate cancer followed by radical prostatectomy: correlation of treatment effects with imaging

Contains fulltext : 174147.pdf (publisher's version ) (Open Access)PURPOSE: To correlate treatment effects of MRI-guided focal laser ablation in patients with prostate cancer with imaging using prostatectomy as standard of reference. METHODS: This phase I study was approved by the Institutional Review Board. Three weeks prior to prostatectomy, five patients with histopathologically proven, low/intermediate grade prostate cancer underwent transrectal MRI-guided focal laser ablation. Per patient, only one ablation was performed to investigate the effect of ablation on the tissue rather than the effectiveness of ablation. Ablation was continuously monitored with real-time MR temperature mapping, and damage-estimation maps were computed. A post-ablation high-resolution T1-weighted contrast-enhanced sequence was acquired. Ablation volumes were contoured and measured on histopathology specimens (with a shrinkage factor of 1.15), T1-weighted contrast-enhanced images, and damage-estimation maps, and were compared. RESULTS: A significant volume correlation was seen between the ablation zone on T1-weighted contrast-enhanced images and the whole-mount histopathology section (r = 0.94, p = 0.018). The damage-estimation maps and histopathology specimen showed a correlation of r = 0.33 (p = 0.583). On histopathology, the homogeneous necrotic area was surrounded by a reactive transition zone (1-5 mm) zone, showing neovascularisation, and an increased mitotic index, indicating increased tumor activity. CONCLUSIONS: The actual ablation zone was better indicated by T1-weighted contrast-enhanced than by damage-estimation maps. Histopathology results highlight the importance of complete tumor ablation with a safety margin

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis

Contains fulltext : 191559.pdf (publisher's version ) (Open Access

State-of-the-art uroradiologic imaging in the diagnosis of prostate cancer

Contains fulltext : 98365.pdf (publisher's version ) (Closed access)In the diagnostic process of prostate cancer, several radiologic imaging modalities significantly contribute to the detection and localization of the disease. These range from transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) to positron emission tomography (PET). Within this review, after evaluation of the literature, we will discuss the advantages and disadvantages of these imaging modalities in clarifying the patient's clinical status as to whether he has prostate cancer or not and if so, where it is located, so that therapy appropriate to the patient's disease may be administered. TRUS, specifically with the usage of intravenous contrast agents, provides an excellent way of directing biopsy towards suspicious areas within the prostate in the general (screening) population. MRI using functional imaging techniques allows for highly accurate detection and localization, particularly in patients with prior negative ultrasound guided biopsies. A promising new development is the performance of biopsy within the magnetic resonance scanner. Subsequently, a proposal for optimal use of radiologic imaging is presented and compared with the European and American urological guidelines on prostate cancer