Reciprocal virulence and resistance polymorphism in the relationship betweenToxoplasma gondiiand the house mouse

Virulence in the ubiquitous intracellular protozoon Toxoplasma gondii for its natural intermediate host, the mouse, appears paradoxical from an evolutionary standpoint because death of the mouse before encystment interrupts the parasite life cycle. Virulent T. gondii strains secrete kinases and pseudokinases that inactivate the immunity-related GTPases (IRG proteins) responsible for mouse resistance to avirulent strains. Such considerations stimulated a search for IRG alleles unknown in laboratory mice that might confer resistance to virulent strains of T. gondii. We report that the mouse IRG system shows extraordinary polymorphic complexity in the wild. We describe an IRG haplotype from a wild-derived mouse strain that confers resistance against virulent parasites by interference with the virulent kinase complex. In such hosts virulent strains can encyst, hinting at an explanation for the evolution of virulence polymorphism in T. gondii. DOI:http://dx.doi.org/10.7554/eLife.01298.001.Deutsche Forschungsgemeinschaft (SFB 680, SFB 635, SFB 670, SPP 1399), International Graduate School in Development Health and Disease

EMT Markers in Locally-Advanced Prostate Cancer: Predicting Recurrence?

Background: Prostate cancer (PCa) is the second most frequent cause of cancer-related death in men worldwide. It is a heterogeneous disease at molecular and clinical levels which makes its prognosis and treatment outcome hard to predict. The epithelial-to-mesenchymal transition (EMT) marks a key step in the invasion and malignant progression of PCa. We sought to assess the co-expression of epithelial cytokeratin 8 (CK8) and mesenchymal vimentin (Vim) in locally-advanced PCa as indicators of EMT and consequently predictors of the progression status of the disease.Methods: Co-expression of CK8 and Vim was evaluated by immunofluorescence (IF) on paraffin-embedded tissue sections of 122 patients with PCa who underwent radical prostatectomies between 1998 and 2016 at the American University of Beirut Medical Center (AUBMC). EMT score was calculated accordingly and then correlated with the patients' clinicopathological parameters and PSA failure.Results: The co-expression of CK8/Vim (EMT score), was associated with increasing Gleason group. A highly significant linear association was detected wherein higher Gleason group was associated with higher mean EMT score. In addition, the median estimated biochemical recurrence-free survival for patients with < 25% EMT score was almost double that of patients with more than 25%. The validity of this score for prediction of prognosis was further demonstrated using cox regression model. Our data also confirmed that the EMT score can predict PSA failure irrespective of Gleason group, pathological stage, or surgical margins.Conclusion: This study suggests that assessment of molecular markers of EMT, particularly CK8 and Vim, in radical prostatectomy specimens, in addition to conventional clinicopathological prognostic parameters, can aid in the development of a novel system for predicting the prognosis of locally-advanced PCa

A Cost-Utility Analysis of Prostate Cancer Screening in Australia

Background and Objectives: The Göteborg randomised population-based prostate cancer screening trial demonstrated that Prostate Specific Antigen (PSA) based screening reduces prostate cancer deaths compared with an age matched control group. Utilising the prostate cancer detection rates from this study we have investigated the clinical and cost-effectiveness of a similar PSA-based screening strategy for an Australian population of men aged 50-69 years. Methods: A decision model that incorporated Markov processes was developed from a health system perspective.The base case scenario compared a population-based screening programme with current opportunistic screening practices. Costs, utility values, treatment patterns and background mortality rates were derived from Australian data. All costs were adjusted to reflect July 2015 Australian dollars. An alternative scenario compared systematic with opportunistic screening but with optimisation of active surveillance (AS) uptake in both groups. A discount rate of 5% for costs and benefits was utilised. Univariate and probabilistic sensitivity analyses were performed to assess the effect of variable uncertainty on model outcomes. Results: Our model very closely replicated the number of deaths from both prostate cancer and background mortality in the Göteborg study. The incremental cost per quality-adjusted life-year (QALY) for PSA screening was $AU147,528. However, for years of life gained (LYGs) PSA based screening ($AU45,890/LYG) appeared more favourable. Our alternative scenario with optimised AS improved cost-utility to $AU45,881/QALY, with screening becoming cost-effective at a 92$AU50,000/QALY. It appears more cost-effective if LYGs are used as the relevant outcome, and is more cost effective than the established Australian breast cancer screening programme on this basis. Optimised utilisation of AS increases the cost-effectiveness of prostate cancer screening dramatically

Laparoscopic treatment of giant renal cystic echinococcosis

Hydatid disease is a parasitic infestation caused by the larval form of the cestode Echinococcus granulosus. Isolated renal involvement is quite rare. Surgery is the mainstay of treatment and is classically performed through an open approach with kidney-sparing when feasible. The case of a 33-year-old male patient who underwent laparoscopic unroofing of a giant renal hydatid cyst is described herein

Crossed Unfused Ectopic Pelvic Kidneys: A Case Illustration

Crossed unfused ectopia constitutes a very rare variant of ectopic kidneys, with an approximate incidence of 1 : 75000. We hereby describe a rare case of an incidental finding of crossed unfused ectopic kidneys, in a 45-year-old gentleman incidentally found to have a bladder lesion. The unique blood supply of his kidneys has also been described. The present case also highlights the different subtypes of renal ectopia, the different embryological hypotheses behind their presentation, and the various systematic anomalies, associated with them. Variations in vasculature of ectopic kidneys have been only described in case reports and are crucial to recognize in case any further intervention is needed

Preoperative predictors of prolonged length of stay in radical cystectomy: a retrospective study using the American College of Surgeons-National Surgical Quality Improvement Program Dataset

Background: Radical cystectomy (RC) is considered a complex procedure that entails significant morbidity and mortality. Objectives: We aimed to determine pre-operative patient characteristics that help predict a prolonged length of hospital stay (PLOS) following RC. Design and Methods: The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database was used to select patients who underwent RC between the years 2011 and 2020. Prolonged length of stay was defined as a hospital stay ⩾9 days. We compared patient demographics, pre-operative labs, surgical characteristics, and medical history between patients with or without PLOS. Multivariable logistic regression models controlling for pre-operative characteristics and propensity score matching for post-operative complications were conducted to control for possible confounders. Results: The analysis yielded details of 19,158 RC patients of which 6007 (31%) patients had a PLOS. Patients with PLOS were more likely to have post-operative complications that could serve as predictors for the PLOS rather than their pre-operative characteristics. Hence, we matched our cohort for these complications. After matching, patient pre-operative characteristics that predict PLOS included female gender (Odds Ratio (OR) = 5.91), 10-year increase in age (OR = 1.15), non-White race (OR = 1.98), partially or totally dependent functional health status (OR = 2.86), bleeding disorders (OR = 4.67), congestive heart failure (OR = 1.59), pre-operative transfusion (OR = 3.03), and a 20-min increase in operative time (OR = 1.01) ( p < 0.046). Conclusion: Patient demographics and pre-operative factors can help predict PLOS in RC patients. These predictors could serve as tools for patient counseling and risk stratification

Sedation as an alternative anesthetic technique for frail patients in transurethral resection of the prostate

Background: Transurethral resection of the prostate (TURP) under Monitored Anesthesia Care MAC/Sedation (macTURP), as compared with TURP under general (genTURP) or spinal (spTURP) anesthesia, is a safer and infrequently used technique reserved for high-risk patients. Objectives: The aim of this study is to compare 30-day postoperative outcomes of TURP using the three types of anesthesia techniques. Design and methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients who underwent TURP between 2008 and 2019. Demographics, lab values, medical history, and 30-day outcomes were compared. Univariate and multivariate regression models for postoperative complications were constructed. A propensity score–matched analysis was then performed for genTURP and macTURP and for spTURP and macTURP as a sensitivity analysis. Results: A total of 53,182 patients underwent TURP. Older patients (>80) with diabetes requiring insulin (7.9%), leukocytosis (7.4%), history of chronic obstructive pulmonary disease (COPD) (7.8%), dyspnea (7.2%), and of ASA > 2 (58.8%) were more likely to undergo macTURP as compared with genTURP ( p  < 0.013). SpTURP showed lower rates of urinary tract infection (UTI) [odds ratio (OR) = 0.869] as compared with genTURP ( p  = 0.049), whereas macTURP showed higher rates of major adverse cardiovascular events (OR = 2.179) as compared with genTURP ( p  = 0.005). All other postoperative complications showed similar rates between the three procedures. The propensity-matched cohorts demonstrated that no differences in postoperative complication rates were noted between macTURP and genTURP and between macTURP and spTURP. Conclusion: MacTURP was found to be feasible with a good safety profile as compared with genTURP and spTURP. MacTURP could be used in elderly, frail, and co-morbid patients with a similar safety profile as compared with more invasive anesthetic techniques

The 5-item frailty index predicts 30-day morbidity and mortality in radical nephrectomy patients: A propensity matched analysis

PURPOSE: To assess the ability of the 5-item frailty index (5-IFi) score to predict 30-day morbidity and mortality post-radical nephrectomy (RN). METHODS: ACS-NSQIP database was used to select patients who underwent RN from 2011 to 2020. 5-IFi score was calculated by assigning a point for each of the following comorbidities: chronic obstructive pulmonary disease or pneumonia, congestive heart failure, dependent functional status, hypertension, and diabetes. Patients were divided into 3 frailty groups 0, 1, and ≥2. Patient demographics, medical comorbidities, prolonged length of stay, and prolonged operative time were compared between different groups; mortality and morbidity using the Clavien-Dindo classification (CVD). Multivariable logistic regression models and propensity score matching were performed as a sensitivity analysis to control for possible confounders. RESULTS: Cohort consisted of 36,682 patients whereby 5-IFi class 0, 1, and ≥2 included 11,564 (31.5%), 16,571 (45.2%), and 8,547 (25.3%) patients respectively. A multivariable analysis and propensity score matching revealed that patients with 5-IFi classes 1 and ≥ 2 were more likely to have a prolonged length of stay (OR = 1.11, 1.3, respectively) and to mortality (OR = 1.85 for frailty class ≥2); in addition to CVD class 1 & 2 (OR = 1.51, OR = 1.13, respectively), and CVD ≥ 4 (OR = 1.41, 1.86, respectively) as compared to 5-IFi class 0 (P \u3c 0.001). CONCLUSION: The 5-IFi score was found to be an independent predictor of prolonged length of stay, morbidity, and mortality after RN. This tool can play a major role in preoperative risk assessment and patient counseling based on individualized risks

Robotic-assisted radical prostatectomy is pushing the boundaries: a national survey of frailty using the national surgical quality improvement program

Background: Robotic-assisted radical prostatectomy (RARP) has been found to be comparable and, in some cases, favorable to open surgical approaches, while being used in a frailer population. Objectives: We aimed to illustrate the trend in population frailty and compare morbidity and mortality postoperatively in patients who underwent RARP. Design and Methods: The National Surgical Quality Improvement Program data set was used to select patients who underwent RARP between the years 2011–2019. Age, frailty indicators, surgical characteristics, and perioperative morbidity and mortality were compared between the years 2011–2019 using the chi-square test (χ 2 ) for categorical variables and the one-way analysis of variance (ANOVA) for continuous variables. Results: Our patient population consisted of 66,683 patients who underwent RARP. There was an increase in mean age and frailty indicated by an increase in 5-item frailty score ⩾2, metabolic syndrome index = 3, and American Society of Anesthesiologists’ (ASA) class ⩾3 between the years 2011–2019 ( p   0.264). Furthermore, operative time and length of stay decreased over the same period ( p  < 0.001). Conclusion: RARP is being performed on more frail patients, with no added morbidity or mortality