Legacy contaminant trends in the Great Lakes uncovered by the wildlife environmental quality index.

Since the 1970s, wildlife managers have prioritized the recovery of Great Lakes ecosystems from contamination by Persistent Organic Pollutants (POPs). Monitoring and quantifying the region's recovery is challenged by the diversity of legacy contaminants in the environment and the lack of benchmarks for their potential biological effects. We address this gap by introducing the Wildlife Environmental Quality Index (WEQI) based on prior water and sediment quality indices. The tool summarizes, in a single score, the exposure of wildlife to harmful levels of multiple contaminants - with harmful levels set by published guidelines for protecting piscivorous wildlife from biological impacts. We applied the new index to a combined Canadian and American dataset of Herring Gull (Larus argentatus) egg data to elucidate trends in wildlife for eight legacy industrial pollutants and insecticides in the Great Lakes. Environmental quality of the Great Lakes region (as indexed by WEQI) improved by 18% between 2002 and 2017. Improvement came from reductions in both the scope of contamination (the number of guideline-exceeding contaminants) and its amplitude (the average size of guideline exceedances) at bird colonies. But recovery was unequal among lakes, with Lake Erie showing no improvement at one extreme. Weakly- or non-recovering lakes (Erie, Ontario, Huron) were marked by inconsistent improvement in scope and amplitude, likely due to ongoing loading, sediment resuspension and other stressors reported elsewhere. Fast-recovering lakes (Superior and Michigan), meanwhile, improved in both scope and amplitude. Contrasting trends and contaminant profiles (e.g., exceedances of PCBs versus DDTs) highlight the importance of lake-specific management for equalizing recoveries. Lower environmental quality at American than Canadian colonies, particularly in Lake Huron, further suggest uneven success in - and opportunities for - the binational management of wildlife exposure to legacy contaminants.

Robot-Assisted Repair of Bladder Rupture following Penile Ring Entrapment.

Penile rings have been used to help sustain erection and enhance sexual pleasure for centuries. Constriction of the penis reduces the outflow of blood from the cavernosal tissue. However, if left for an extended time period, a condition called penile ring entrapment can occur. This may result in severe edema, gangrene, necrosis, and even penile amputation. Penile ring entrapment is a very rare condition; complete urinary obstruction with concomitant bladder rupture as a result renders this case even more extraordinary. We discuss our experience in the management of a 64-year-old man, who presented with altered mental status and inability to urinate, found to have penile ring entrapment and intraperitoneal bladder rupture. Removal of the constricting ring was performed in the ED, and bladder injury and penile necrosis were subsequently repaired with robot-assisted laparoscopic cystorrhaphy, penectomy, and perineal urethrostomy.

Artificial intelligence quantifying endoscopic severity of ulcerative colitis in gradation scale.

OBJECTIVES: Existing endoscopic scores for ulcerative colitis (UC) objectively categorize disease severity based on the presence or absence of endoscopic findings; therefore, it may not reflect the range of clinical severity within each category. However, inflammatory bowel disease (IBD) expert endoscopists categorize the severity and diagnose the overall impression of the degree of inflammation. This study aimed to develop an artificial intelligence (AI) system that can accurately represent the assessment of the endoscopic severity of UC by IBD expert endoscopists. METHODS: A ranking-convolutional neural network (ranking-CNN) was trained using comparative information on the UC severity of 13,826 pairs of endoscopic images created by IBD expert endoscopists. Using the trained ranking-CNN, the UC Endoscopic Gradation Scale (UCEGS) was used to express severity. Correlation coefficients were calculated to ensure that there were no inconsistencies in assessments of severity made using UCEGS diagnosed by the AI and the Mayo Endoscopic Subscore, and the correlation coefficients of the mean for test images assessed using UCEGS by four IBD expert endoscopists and the AI. RESULTS: Spearman's correlation coefficient between the UCEGS diagnosed by AI and Mayo Endoscopic Subscore was approximately 0.89. The correlation coefficients between IBD expert endoscopists and the AI of the evaluation results were all higher than 0.95 (P < 0.01). CONCLUSIONS: The AI developed here can diagnose UC severity endoscopically similar to IBD expert endoscopists.

Randomised clinical trial: a phase 1b study of GB004, an oral HIF-1α stabiliser, for treatment of ulcerative colitis.

BACKGROUND: Epithelial barrier dysfunction contributes to a dysregulated intestinal immune response in ulcerative colitis (UC). GB004 is an orally administered, small molecule, gut-targeted stabiliser of hypoxia-inducible factor-1α, a transcription factor with protective roles at the epithelial layer of the inflamed gut. AIMS: To evaluate safety, pharmacokinetics, pharmacodynamics and efficacy of GB004 in patients with active UC. METHODS: This double-blind, placebo-controlled study randomised patients 2:1 to receive an oral solution of GB004 120 mg or placebo once daily for 28 days. Eligible patients had a Robarts Histopathology Index score ≥4 with neutrophils in the epithelium, total Mayo Clinic score 3-12, Mayo Clinic endoscopic subscore ≥1, and blood in the stool, despite treatment with 5-aminosalicylates, corticosteroids or immunosuppressants. RESULTS: Thirty-four patients were randomised. GB004 120 mg for 28 days was generally well-tolerated. Adverse events occurred in 27.3% (3/11) and 39.1% (9/23) of patients in the placebo and GB004 groups respectively. Nausea and dysgeusia were most commonly reported in the GB004 group (0% for placebo and 21.7% [5/23] and 13.0% [3/23] respectively for GB004). There were no treatment-related serious adverse events or deaths. GB004 exhibited minimal accumulation, with higher colonic concentrations relative to plasma. Exploratory pharmacodynamic and efficacy analyses demonstrated GB004 target engagement and numerically higher proportions of patients achieving improvement in multiple measures of disease activity, respectively, at day 28 for GB004 compared to placebo. CONCLUSION: Results from this phase 1b trial support evaluation of the full therapeutic potential of GB004 for the treatment of UC. A phase 2 study (NCT04556383) is ongoing. Clinicaltrials.gov NCT03860896.

Role of the androgen, estrogen, and progesterone receptors in adherent perinephric fat in robotic partial nephrectomy.

To determine whether androgen, estrogen, and/or progesterone signaling play a role in the pathophysiology of adherent perinephric fat (APF). We prospectively recruited patients undergoing robotic assisted partial nephrectomy during 2015-2017. The operating surgeon documented the presence or absence of APF. For those with clear cell renal cell carcinoma (ccRCC), representative sections of tumor and perinephric fat were immunohistochemically stained with monoclonal antibody to estrogen α, progesterone, and androgen receptors. Patient characteristics, operative data, and hormone receptor presence were compared between those with and without APF. Of 51 patients total, 18 (35.3%) and 33 (64.7%) patients did and did not have APF, respectively. APF was associated with history of diabetes mellitus (61.1% vs 24.2%, p = 0.009) and larger tumors (4.0 cm vs 3.0 cm, p = 0.017) but not with age, gender, BMI, Charleston comorbidity index, smoking, or preoperative estimated glomerular filtration rate. APF was not significantly associated with length of operation, positive margins, or 30-day postoperative complications but incurred higher estimated blood loss (236.5 mL vs 209.2 mL, p = 0.049). Thirty-two had ccRCC and completed hormone receptor staining. The majority of tumors and perinephric fat were negative for estrogen and progesterone while positive for androgen receptor expression. There was no difference in hormone receptor expression in either tumor or perinephric fat when classified by presence or absence of APF (p > 0.05). APF is more commonly present in patients with diabetes or larger tumors but was not associated with differential sex hormone receptor expression in ccRCC.

Femoral-Femoral Bypass for Limb Salvage to Correct Common Iliac Occlusion after Lower Extremity Trauma.

BACKGROUND: Roadway injuries are a leading cause of lower extremity vascular trauma. Treating these injuries involves controlling life-threatening hemorrhage and restoring distal perfusion. MATERIALS AND METHODS: We describe a unique presentation of chronic iliac artery occlusion in the setting of blunt trauma requiring extra-anatomic bypass for maximal limb salvage. RESULTS: A 50-year-old male presented after a pedestrian versus auto accident. He had mangled bilateral lower extremities and was taken emergently for lower extremity amputations. He was found to have chronic left common iliac occlusion and a femoral-femoral bypass was performed to assist with healing his left below-the-knee amputation. DISCUSSION: Lack of adequate perfusion can cause poor outcomes in limb salvage. This case demonstrated that lower extremity trauma can be complicated by chronic vascular disease. Reperfusion and adequate wound healing can be accomplished by using bypass grafting after more traditional reperfusion techniques fail.

Women's experiences of early pregnancy assessment unit services: a qualitative investigation.

OBJECTIVE: To explore the experiences of women who had used an Early Pregnancy Assessment Unit (EPAU) service in the UK and make recommendations for their improvement. DESIGN: Qualitative interview study. SETTING: Early Pregnancy Assessment Units in the UK. SAMPLE: A maximum variation sample of women who had consented to be interviewed having attended one of 26 EPAUs involved in the VESPA study in 2018. METHODS: In-depth telephone interviews with 38 women. A thematic framework analysis was conducted, with a focus on how experiences varied according to EPAU service configuration and clinical pathway. MAIN OUTCOME MEASURES: Women's experiences of EPAU services. RESULTS: We found that EPAUs are highly valued, and women's experiences were generally positive. However, women reported a range of issues that negatively affected their experience. These included difficulties accessing the service, insensitive management of the investigation and treatment options of pregnancy loss, poor communication, insufficient information and a lack of support for their psychological health. These issues were not strongly associated with EPAU configuration or clinical pathway. CONCLUSIONS: Recommendations to improve women's experiences include the separation of EPAUs from general maternity services, and we make suggestions on how to remove barriers to access by reviewing opening hours, how to provide sensitive patient management, such as automatically cancelling appointments and scans following pregnancy loss, and how to improve communication, both with women and their partners as well as with other parts of the health service. TWEETABLE ABSTRACT: Early Pregnancy Assessment Units are highly valued by women but aspects of their care experiences, particularly around sensitive management of pregnancy loss, could be improved.

Progress in Corticosteroid Use in the Era of Biologics With Room for Improvement.

ABSTRACT: With the early success of their trials for the treatment of ulcerative colitis, corticosteroids gained popularity as a treatment for inflammatory bowel disease (IBD). However, when used chronically, corticosteroids are not effective in maintaining remission and associated with toxic effects. Steroid-free remission has become a major treatment goal. Prolonged corticosteroid use is currently a sign of suboptimal quality of care. Trends over the past 2 decades, spanning the emergence of biologic therapies for IBD, are explored here in the University of Manitoba IBD Epidemiologic Database.

Safety of retrograde pyelography for infected ureteral stones.

INTRODUCTION: Initial management of obstructing ureteral stones with concomitant urinary tract infection (UTI) includes prompt renal decompression and antibiotics. Some urologists theorize that performing retrograde pyelography (RGP) at the time of ureteral stent placement may cause pyelovenous backflow of bacteria thereby worsening clinical outcomes. We compared outcomes in patients with infected ureteral stones who underwent RGP versus no RGP prior to stent placement. MATERIALS AND METHODS: A retrospective chart review was conducted involving patients who presented between 2015 and 2017 with an obstructing ureteral stone and associated UTI. Computed tomography scans were evaluated for stone size and location. Operative reports were reviewed to determine whether the patient underwent RGP at time of ureteral stent placement. Demographics, perioperative information, intensive care unit (ICU) admission rate, and length of stay (LOS) were compared. RESULTS: Seventy-two patients were identified and stratified by severity of condition at presentation, including UTI without sepsis (n = 18), sepsis (n = 32), severe sepsis (n = 11), and septic shock (n = 11). Forty-three patients underwent RGP at the time of stent placement, and 29 did not. Between both patient cohorts, statistical analysis revealed no significant difference in postoperative ICU admission rate (p = 0.35) or LOS for patients with UTI without sepsis (p = 0.17), sepsis (p = 0.45), severe sepsis (p = 0.66), and septic shock (p = 0.25). CONCLUSION: The use of RGP prior to ureteral stent placement for an obstructing ureteral stone with concomitant UTI was not associated with unfavorable clinical outcomes in our retrospective series. While these findings support the safety of RGP in this setting, prospective trials are warranted.

On the Stability of Reported Pregnancy Intentions from Pregnancy to 1 Year Postnatally: Impact of Choice of Measure, Timing of Assessment, Women's Characteristics and Outcome of Pregnancy.

OBJECTIVES: Retrospective, cross-sectional estimates of pregnancy intention, as used in the Demographic Health Survey (DHS), are the global norm. The London Measure of Unplanned Pregnancy (LMUP) is a newer, psychometrically validated measure which may be more reliable. This paper assesses the reliability of the LMUP and the DHS question over the first postnatal year and explores the effects of maternal characteristics or pregnancy outcome on reported pregnancy intention. METHODS: We compared the test-retest reliability of the LMUP (using the AC coefficient) and DHS question (using the weighted Kappa) over the first postnatal year using data from Malawian women. We investigated the effect of maternal characteristics and pregnancy outcome using t-tests, Chi squared or Fisher's exact tests, and calculated odds ratios to estimate effect size. RESULTS: The DHS question was associated with a statistically significant decrease in the prevalence of unplanned pregnancies from 1-to-12 months postnatally; the LMUP was not. The LMUP had moderate to substantial reliability (0.51-0.66); the DHS had moderate reliability (0.56-0.58). The LMUP's stability was not related to any of the factors examined; the stability of the DHS varied by marital status (p = 0.033), number of children (p = 0.048) and postnatal depression (p < 0.001). Both underestimated unintended pregnancy postnatally vis-à-vis the LMUP in pregnancy. CONCLUSIONS FOR PRACTICE: The LMUP is a more reliable measure of pregnancy intention than the DHS in the first postnatal year and does not vary by maternal characteristics or pregnancy outcome. The LMUP should become the gold-standard for measuring pregnancy intention and should be collected in pregnancy or at the first postnatal opportunity.

Comparing Off-clamp and On-clamp Robot-assisted Partial Nephrectomy: A Prospective Randomized Trial.

OBJECTIVE: To determine whether performing robot-assisted partial nephrectomy without warm ischemia "off-clamp" results in favorable postoperative renal functional outcomes compared with the on-clamp method. METHODS: We conducted a prospective trial of 80 patients who underwent robot-assisted partial nephrectomy. They were randomized in a 1:1 ratio to undergo the procedure with renal artery clamping or without clamping. The groups were compared across demographics, operative information, perioperative outcomes, and postoperative renal function. We assessed renal function by estimated glomerular filtration rate and renal scintigraphy both preoperatively and at 3 months postoperatively. RESULTS: Patients in the on-clamp and off-clamp groups were similar in age, gender, body mass index, comorbidities, clinical tumor size, nephrometry score, and laterality. Off-clamp procedures were lengthier at an average 178.0 minutes vs 156.0 minutes for on-clamp (P = .011). Estimated blood loss, rates of pelvicalyceal repair, postoperative complications, and positive margins were not different. At a median 3-month follow-up, no significant differences were seen in change in postoperative estimated glomerular filtration rate or percent split renal function between both groups. CONCLUSION: In this prospective study, off-clamp robot-assisted partial nephrectomy resulted in similar perioperative outcomes compared with the on-clamp technique. No benefit was demonstrated in the preservation of renal function. Urologists may safely employ either an on-clamp or off-clamp strategy depending on surgeon preference and patient-specific factors including baseline renal insufficiency, multiple masses, or solitary kidney.

Performance of Crohn's disease Clinical Trial Endpoints based upon Different Cutoffs for Patient Reported Outcomes or Endoscopic Activity: Analysis of EXTEND Data.

Background: Clinical trial endpoints for Crohn's disease (CD) activity correlate poorly with mucosal inflammation; to assess treatment efficacy, patient-reported outcomes and endoscopic assessments are preferred. This study assessed the impact on treatment efficacy estimations of using different definitions of clinical and endoscopic remission and endoscopic response, and of using site- or central-based endoscopy evaluation. Methods: This post hoc analysis of data fromEXTEND (extend the safety and efficacy of adalimumab through endoscopic healing), a placebo (PBO)-controlled, randomized trial of adalimumab (ADA) for mucosal healing, included adults with moderate-to-severe CD. Subsets of patients meeting specified Simplified Endoscopic Score for CD (SES-CD) inclusion criteria, according to site or central reading, and baseline stool frequency (SF) and/or abdominal pain score (AP) thresholds were evaluated. Various endpoint definitions based on the Crohn's Disease Activity Index (CDAI), its SF and AP components, SES-CD, and composite endpoints were compared between treatment groups. Results: Increased stringency of Week 12 clinical endpoints compared to CDAI<150 to SF≤3.0/1.5&AP≤1.0 reduced PBO response rates by ≥12% and increased treatment effects by ≤10%. Amending the SES-CD endpoint from ≤4 to ≤2 reduced the treatment effect from 24% to 8%. Composite endpoints further diminished response rates and effect sizes. Site-based evaluation was associated with lower remission rates versus central reading in the PBO group and, thus, greater ADA-related treatment effects. Conclusions: This analysis is the first to demonstrate that increasing the stringency of clinical and endoscopic endpoint definitions in CD trials, especially lowering SF or SES-CD definitions, reduces the ability to detect treatment-related change in CD activity; focus on endpoints that reflect clinical change is warranted.

Development of Reliable, Valid and Responsive Scoring Systems for Endoscopy and Histology in Animal Models for Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Although several endoscopic and histopathologic indices are available for evaluating the severity of inflammation in mouse models of colitis, the reliability of these scoring instruments is unknown. Our aim was to evaluate the reliability of the individual items in the existing indices and develop new scoring systems by selection of the most reliable index items. METHODS: Two observers scored the histological slides [n = 224] and endoscopy videos [n = 201] from treated and untreated Interleukin[IL]-10 knock-out and T-cell transferred SCID mice. Intra-rater and inter-rater reliability for endoscopy and histology scores, and each individual item, were measured using intraclass correlation coefficients [ICCs]. The Mouse Colitis Histology Index [MCHI] and Mouse Colitis Endoscopy Index [MCEI] were developed using the most reliable items. Both were correlated to the colon density and to each other and were evaluated for their ability to detect changes in pathobiology. RESULTS: The intraclass correlation coefficients (ICCs) for inter-rater agreement (95% CIs) for the total histology and endoscopy scores were 0.90 [0.87-0.92] and 0.80 [0.76-0.84], respectively. The MCHI and MCEI were highly correlated with colon density, with a Spearman Rho = 0.81[0.75-0.85] and 0.73 [0.66-0.79], respectively, and with each other, Spearman Rho = 0.71 [0.63-0.77]. The MCHI and MCEI were able to distinguish between the experimental groups within the models, with pairwise differences between the treated and untreated groups being statistically significant [p < 0.001]. CONCLUSIONS: These histological and endoscopic indices are valid and reliable measures of intestinal inflammation in mice, and they are responsive to treatment effects in pre-clinical studies.

Development and Validity of a Silicone Renal Tumor Model for Robotic Partial Nephrectomy Training.

OBJECTIVE: To provide a training tool to address the technical challenges of robot-assisted laparoscopic partial nephrectomy, we created silicone renal tumor models using 3-dimensional printed molds of a patient's kidney with a mass. In this study, we assessed the face, content, and construct validity of these models. MATERIALS AND METHODS: Surgeons of different training levels completed 4 simulations on silicone renal tumor models. Participants were surveyed on the usefulness and realism of the model as a training tool. Performance was measured using operation-specific metrics, self-reported operative demands (NASA Task Load Index [NASA TLX]), and blinded expert assessment (Global Evaluative Assessment of Robotic Surgeons [GEARS]). RESULTS: Twenty-four participants included attending urologists, endourology fellows, urology residents, and medical students. Post-training surveys of expert participants yielded mean results of 79.2 on the realism of the model's overall feel and 90.2 on the model's overall usefulness for training. Renal artery clamp times and GEARS scores were significantly better in surgeons further in training (P ≤.005 and P ≤.025). Renal artery clamp times, preserved renal parenchyma, positive margins, NASA TLX, and GEARS scores were all found to improve across trials (P <.001, P = .025, P = .024, P ≤.020, and P ≤.006, respectively). CONCLUSION: Face, content, and construct validity were demonstrated in the use of a silicone renal tumor model in a cohort of surgeons of different training levels. Expert participants deemed the model useful and realistic. Surgeons of higher training levels performed better than less experienced surgeons in various study metrics, and improvements within individuals were observed over sequential trials. Future studies should aim to assess model predictive validity, namely, the association between model performance improvements and improvements in live surgery.