Defining a national reference level for intraoperative radiation exposure in urological procedures: FLASH, a retrospective multicentre UK study.

OBJECTIVES: To define reference levels for intraoperative radiation during stent insertion, ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL); to identify variation in radiation exposure between individual hospitals across the UK, between low- and high-volume PCNL centres, and between grade of lead surgeon. PATIENTS/SUBJECTS AND METHODS: In all, 3651 patients were identified retrospectively across 12 UK hospitals over a 1-year period. Radiation exposure was defined in terms of total fluoroscopy time (FT) and dose area product (DAP). The 75th percentiles of median values for each hospital were used to define reference levels for each procedure. RESULTS: Reference levels: ureteric stent insertion/replacement (DAP, 2.3 Gy/cm2 ; FT, 49 s); URS (DAP, 2.8 Gy/cm2 ; FT, 57 s); PCNL (DAP, 24.1 Gy/cm2 ; FT, 431 s). Significant variations in the median DAP and FT were identified between individual centres for all procedures (P < 0.001). For PCNL, there was a statistically significant difference between DAP for low- (<50 cases/annum) and high-volume centres (>50 cases/annum), at a median DAP of 15.0 Gy/cm2 vs 4.2 Gy/cm2 (P < 0.001). For stent procedures, the median DAP and FT differed significantly between grade of lead surgeon: Consultant (DAP, 2.17 Gy/cm2 ; FT, 41 s) vs Registrar (DAP, 1.38 Gy/cm2 ; FT, 26 s; P < 0.001). CONCLUSION: This multicentre study is the largest of its kind. It provides the first national reference level to guide fluoroscopy use in urological procedures, thereby adding a quantitative and objective value to complement the principles of keeping radiation exposure 'as low as reasonably achievable'. This snapshot of real-time data shows significant variation around the country, as well as significant differences between low- and high-volume centres for PCNL, and grade of lead surgeon for stent procedures.

Structural Correlates of Overt Sentence Reading in Mild Cognitive Impairment and Mild-to-Moderate Alzheimer's Disease.

BACKGROUND: Overt sentence reading in mild cognitive impairment (MCI) and mild-tomoderate Alzheimer's disease (AD) has been associated with slowness of speech, characterized by a higher number of pauses, shorter speech units and slower speech rate and attributed to reduced working memory/ attention and language capacity. OBJECTIVE: This preliminary case-control study investigates whether the temporal organization of speech is associated with the volume of brain regions involved in overt sentence reading and explores the discriminative ability of temporal speech parameters and standard volumetric MRI measures for the classification of MCI and AD. METHODS: Individuals with MCI, mild-to-moderate AD, and healthy controls (HC) had a structural MRI scan and read aloud sentences varying in cognitive-linguistic demand (length). The association between speech features and regional brain volumes was examined by linear mixed-effect modeling. Genetic programming was used to explore the discriminative ability of temporal and MRI features. RESULTS: Longer sentences, slower speech rate, and a higher number of pauses and shorter interpausal units were associated with reduced volumes of the reading network. Speech-based classifiers performed similarly to the MRI-based classifiers for MCI-HC (67% vs. 68%) and slightly better for AD-HC (80% vs. 64%) and AD-MCI (82% vs. 59%). Adding the speech features to the MRI features slightly improved the performance of MRI-based classification for AD-HC and MCI-HC but not HC-MCI. CONCLUSION: The temporal organization of speech in overt sentence reading reflects underlying volume reductions. It may represent a sensitive marker for early assessment of structural changes and cognitive- linguistic deficits associated with healthy aging, MCI, and AD.

Association between speech rate measures and cognitive function in people with relapsing and progressive multiple sclerosis.

Background: Cognitive impairments are well-documented in multiple sclerosis (MS), while speech impairments are often overlooked despite their significant effect on quality of life. For effective clinical management of multisystem conditions such as MS, consideration should be given to the interaction between deficits in multiple domains, such as speech and cognition. To evaluate speech rate measures of spontaneous and read speech, in people with MS and to examine the link between speech and cognition. Methods: Forty-five people with MS and 25 controls underwent an extensive cognitive battery, including executive functioning, information processing and memory tasks, and completed two speech tasks: a reading task and a picture description task, from which speech rate measures were derived. Results: The progressive MS cohort had reduced articulation (p < 0.04) and speech rate (p < 0.02) compared to controls and those with relapsing MS. Regression models also revealed information processing speed accounted for 18% to 30% of the variance of spontaneous speech rate measures, and 27% of read speech. Executive functioning accounted for a further 10% of the variance of speech rate in those with MS. Conclusions: The present study suggests that speech production is contingent on cognitive ability, with information processing speed and executive functioning linked with speech timing patterns.

Immunotherapy in Urological Tumors.

The past decade has seen significant improvement in our understanding of tumor biological features, which has led to use of anti-programmed-death 1 (PD-1) and anti-PD-ligand-1 (PD-L1) agents and cytotoxic T lymphocytes antigen 4 (CTLA-4) inhibitors in a multitude of cancers. These immunotherapeutic agents have shown activity in melanoma, lung, head and neck, colorectal, urological, and other cancers. This article details the use of immunotherapy agents in urothelial, renal, prostate, and testicular tumors.

External validation of four nephrometry scores for trans-peritoneal robotic partial nephrectomy.

INTRODUCTION: External validation of four nephrometry scores (NS): Centrality index (C-index), arterial based complexity (ABC), preoperative aspects and dimensions used for an anatomical (PADUA) and radius expohytic/endophytic nearness anterior/posterior location (RENAL) scoring systems in patients who have undergone trans-peritoneal robotic assisted partial nephrectomy (RAPN). MATERIAL AND METHODS: A prospective database for RAPN has been maintained. Individual NSs were performed on 3-dimensional reconstructions of MDCT/MRI studies retrospectively by a board certified uroradiologist. Univariate Cox Proportional-Hazard Regression Analysis was performed for each NSs to valuate its predictability for the following parameters: Warm Ischemia Time (WIT), Estimated Blood Loss (EBL), Operative Time (OT), Complication Rates and Positive Margin Rates. RESULTS: 78 RAPNs were performed for suspected renal malignancies. The mean OT, EBL and WIT time was 186.5 minutes (SD - 33.8), 125.5 mls (SD - 188.91) and 16.7 minutes (SD - 5.6) respectively. The overall complication rate was 20.5% (16/78) of which only 2.6% (2/78) were Clavien Grade 3 or higher complications. The mean change in creatinine change at Day - 1 was 12.54 µmol/L (SD - 18.05). On the Cox regression analysis only the Centrality index predicted prolonged WIT with statistical significance: C-Index (0.02), ABC (0.2), PADUA (0.2), RENAL (0.9). ABC predicted operative time with statistical significance: C-index (0.45), ABC (0.0004), PADUA (0.25), RENAL (0.3). None of the NSs could predict overall complication: C-index (0.5), ABC (0.2), PADUA (0.13), RENAL (0.5). None of the NSs predicted EBL: C-index (0.3)0, ABC (0.8), PADUA (0.2), RENAL (0.7). None of the NSs predicted Positive Margin Rates: C-index (0.4), ABC (0.4), PADUA (0.9), RENAL (0.8). CONCLUSIONS: C-index was able to predict prolonged WIT. ABC was a strong predictor of OT. PADUA and RENAL were poor predictors for all measured parameters.

Practical management of the increasing burden of non-alcoholic fatty liver disease.

Obesity-induced liver disease (non-alcoholic fatty liver disease (NAFLD)) describes a spectrum from steatosis through steatohepatitis to cirrhosis. Its prevalence is rising in tandem with societal rates of obesity which through consequent insulin resistance and fat deposition in hepatocytes lead to hepatocyte death and attempts at repair, which if persistent, lead to activation of liver fibrogenic cells. NAFLD, which may also progress to primary liver cancer, is now the most common cause of chronic liver disease in affluent countries. There is currently no single accurate diagnostic test besides a liver biopsy. The decision to consider a liver biopsy will be informed by the presence of insulin resistance determined by comparatively easy-to-measure factors together with other putative markers of progression such as hypertension. If a liver biopsy is performed, patients with steatosis with no evidence of inflammation may be less aggressively managed while those with steatohepatitis, since they have a faster trajectory to cirrhosis, should be managed more robustly. Besides lifestyle changes and increased aerobic exercise other strategies include considering referral to centres with ongoing clinical trials. Emerging treatments include α1 adrenoceptors antagonists, angiotensin receptor blockers, glitazones and vitamin E.