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Summary Background Radical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision. Methods TREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8–10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743. Findings Between Feb 22, 2012, and Dec 19, 2014, 55 patients were randomly assigned at 15 sites; 27 to organ preservation and 28 to radical surgery. Cumulatively, 18 patients had been randomly assigned at 12 months, 31 at 18 months, and 39 at 24 months. No patients died within 30 days of initial treatment, but one patient randomly assigned to organ preservation died within 6 months following conversion to total mesorectal excision with anastomotic leakage. Eight (30%) of 27 patients randomly assigned to organ preservation were converted to total mesorectal excision. Serious adverse events were reported in four (15%) of 27 patients randomly assigned to organ preservation versus 11 (39%) of 28 randomly assigned to total mesorectal excision (p=0·04, χ2 test). Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in three cases). Radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (two patients), kidney injury (two patients), cardiac arrest (one patient), and pneumonia (two patients). Histopathological features that would be considered to be associated with increased risk of tumour recurrence if observed after transanal endoscopic microsurgery alone were present in 16 (59%) of 27 patients randomly assigned to organ preservation, versus 24 (86%) of 28 randomly assigned to total mesorectal excision (p=0·03, χ2 test). Eight (30%) of 27 patients assigned to organ preservation achieved a complete response to radiotherapy. Patients who were randomly assigned to organ preservation showed improvements in patient-reported bowel toxicities and quality of life and function scores in multiple items compared to those who were randomly assigned to total mesorectal excision, which were sustained over 36 months’ follow-up. The non-randomised registry comprised 61 patients who underwent organ preservation and seven who underwent radical surgery. Non-randomised patients who underwent organ preservation were older than randomised patients and more likely to have life-limiting comorbidities. Serious adverse events occurred in ten (16%) of 61 non-randomised patients who underwent organ preservation versus one (14%) of seven who underwent total mesorectal excision. 24 (39%) of 61 non-randomised patients who underwent organ preservation had high-risk histopathological features, while 25 (41%) of 61 achieved a complete response. Overall, organ preservation was achieved in 19 (70%) of 27 randomised patients and 56 (92%) of 61 non-randomised patients. Interpretation Short-course radiotherapy followed by transanal endoscopic microsurgery achieves high levels of organ preservation, with relatively low morbidity and indications of improved quality of life. These data support the use of organ preservation for patients considered unsuitable for primary total mesorectal excision due to the short-term risks associated with this surgery, and support further evaluation of short-course radiotherapy to achieve organ preservation in patients considered fit for total mesorectal excision. Larger randomised studies, such as the ongoing STAR-TREC study, are needed to more precisely determine oncological outcomes following different organ preservation treatment schedules. Funding Cancer Research UK.

SARS-CoV-2 infection has so far affected over 42 million people worldwide, causing over 1.1 million deaths. With the large majority of SARS-CoV-2 infected individuals being asymptomatic, major concerns have been raised about possible long-term consequences of the infection. We developed an antigen capture assay to detect SARS-CoV-2 spike protein in urine samples from COVID-19 patients whose diagnosis was confirmed by PCR from nasopharyngeal swabs (NP-PCR+). The study used a collection of 233 urine samples from 132 participants from Yale New Haven Hospital and the Children’s Hospital of Philadelphia obtained during the pandemic (106 NP-PCR+ and 26 NP-PCR-) as well as a collection of 20 urine samples from 20 individuals collected before the pandemic. Our analysis identified 23 out of 91 (25%) NP-PCR+ adult participants with SARS-CoV-2 spike S1 protein in urine (Ur-S+). Interestingly, although all NP-PCR+ children were Ur-S-, 1 NP-PCR-child was found to be positive for spike protein in urine. Of the 23 Ur-S+ adults, only 1 individual showed detectable viral RNA in urine. Our analysis further showed that 24% and 21% of NP-PCR+ adults have high levels of albumin and cystatin C in urine, respectively. Among individuals with albuminuria (>0.3 mg/mg of creatinine) statistical correlation could be found between albumin and spike protein in urine. Together, our data showe that 1 of 4 of SARS-CoV-2 infected individuals develop renal abnormalities such as albuminuria. Awareness about the long-term impact of these findings is warranted.

Background: D-dopachrome tautomerase (DDT), the only homolog of macrophage migration inhibitory factor (MIF), is a cytokine highly expressed in cardiomyocytes and exerts autocrine-paracrine effects by signaling through the CD74 receptor. Endogenous DDT and MIF prevent acute ischemia-reperfusion injury and pressure overload-induced heart failure in mice. This study investigated whether endogenous cardiomyocyte DDT has a role in ischemic cardiomyopathy (ICM). Methods: LV tissue was obtained from patients with ICM during heart transplantation and from non-transplanted donor hearts. Plasma DDT concentrations were measured in heart failure outpatients with ICM. Cardiomyocyte-specific DDT knockout (cKO) and littermate control (CON) mice underwent MI or sham surgery. Serial echocardiography was performed to assess LV remodeling after MI or sham surgery. Tissue from the non-infarct region was analyzed 3 days and 4 weeks after MI or sham surgery for histology and molecular studies. Results: Cardiac DDT mRNA and protein expression were reduced in LV from patients transplanted for ICM (n=8). Plasma DDT concentrations below the median value were associated with worse survival in ICM outpatients (p Conclusion: Cardiomyocyte-derived DDT prevents adverse cardiac remodeling in ICM, potentially through modulating mTOR/S6 kinase (adaptive hypertrophy) and p38 MAP kinase (limiting apoptosis). Down-regulation of DDT in patients with ICM may contribute to the pathogenesis of advanced heart failure.

RATIONALE & OBJECTIVE: Acute kidney injury (AKI) is diagnosed based on changes in serum creatinine concentration, a late marker of this syndrome. Algorithms that predict elevated risk for AKI are of great interest, but no studies have incorporated such an algorithm into the electronic health record to assist with clinical care. We describe the experience of implementing such an algorithm. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 2,856 hospitalized adults in a single urban tertiary-care hospital with an algorithm-predicted risk for AKI in the next 24 hours >15%. Alerts were also used to target a convenience sample of 100 patients for measurement of 16 urine and 6 blood biomarkers. EXPOSURE: Clinical characteristics at the time of pre-AKI alert. OUTCOME: AKI within 24 hours of pre-AKI alert (AKI(24)). ANALYTICAL APPROACH: Descriptive statistics and univariable associations. RESULTS: At enrollment, mean predicted probability of AKI(24) was 19.1%; 18.9% of patients went on to develop AKI(24). Outcomes were generally poor among this population, with 29% inpatient mortality among those who developed AKI(24) and 14% among those who did not (P < 0.001). Systolic blood pressure < 100 mm Hg (28% of patients with AKI(24) vs 18% without), heart rate > 100 beats/min (32% of patients with AKI(24) vs 24% without), and oxygen saturation < 92% (15% of patients with AKI(24) vs 6% without) were all more common among those who developed AKI(24). Of all biomarkers measured, only hyaline casts on urine microscopy (72% of patients with AKI(24) vs 25% without) and fractional excretion of urea nitrogen (20% [IQR, 12%−36%] among patients with AKI(24) vs 34% [IQR, 25%−44%] without) differed between those who did and did not develop AKI(24). LIMITATIONS: Single-center study, reliance on serum creatinine level for AKI diagnosis, small number of patients undergoing biomarker evaluation. CONCLUSIONS: A real-time AKI risk model was successfully integrated into the EHR.

Background Diuretic resistance is associated with worse outcomes in acute decompensated heart failure (ADHF). Traditional dogma has held that low cardiac index (CI) is a driver of diuretic resistance by reducing renal perfusion. Recently, accumulating evidence has shown that venous congestion has a more potent effect on cardiorenal interactions than low CI. However, venous congestion also likely identifies patients with increased volume overload and the potential for a greater diuretic response. Hypothesis Right atrial pressure (RAP) will be associated with diuretic response while CI will have little to no association. Methods We analyzed a subset of patients from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) dataset (n=190). Diuretic efficiency (DE) was defined as daily urine output (UOP) per doubling of loop diuretic dose, and compared with baseline, final (day of pulmonary artery catheter (PAC) removal) and change in PAC variables. Daily UOP was additionally examined with time-matched PAC measurements. Results DE was weakly positively correlated with baseline RAP (r=0.16, p=0.03) but negatively correlated with final RAP (r=-0.21, p=0.009) and change in RAP from baseline (r=-0.27, p=0.001). There was no correlation between DE and the remaining PAC variables, including CI. In high vs. low DE groups dichotomized by median value, the low DE group had significantly higher final RAPs (9.0, IQR 6.0-15.5 mmHg vs. 8.0, IQR 4.8-12.0 mmHg, p=0.04) and smaller reductions in RAP (-2.0 mmHg, IQR-5.0-2.0 mmHg vs. -5.0, IQR=-10.0-0.0 mmHg, p=0.03). There were no DE group differences for baseline CI (p=0.78), final CI (p=0.42), or change in CI (p=0.92). There were no significant differences in DE in subjects with CI 2.2 L/min/m2 (p=0.95). Time-matched PAC and UOP data showed a weak positive correlation between RAP and UOP adjusted for diuretic dose (r=0.13, p=0.03), but no correlation between UOP and CI (p=0.18). Conclusions We were unable to identify any association between CI and DE. Higher baseline RAP predicted better DE, but later in the hospital course higher RAP predicted worse DE, likely indicating that elevated RAP is a marker rather than a mediator of diuretic response. Overall, these results suggest that PACs provide limited value in the workup of diuretic resistance.

Introduction Decongestion is the primary therapeutic objective in most acute decompensated heart failure (ADHF) hospitalizations. However, congestion itself commonly represents a barrier to successful diuresis. Renal congestion results in increased renal tubular pressures, reducing glomerular filtration and urine output. This is further aggravated by loop diuretics, which also increase tubular pressures. Because each nephron is a fluid filled column, renal negative pressure treatment (rNPT) applied to the urinary collecting system should reduce tubular pressure, potentially improving kidney function and diuresis. Hypothesis rNPT will improve diuresis, natriuresis, and renal function in a congestion predominate heart failure (CHF) model. Methods Ten ∼80 kg pigs underwent thoracotomy with implantation of a pericardial, Swan Ganz, & bilateral ureteral JuxtaFlow® catheters. High dose furosemide (400mg bolus, then 80mg/hr) was administered since HF clinical use of rNPT will be in conjunction with loop diuretics. Each animal served as its own control with randomization of L vs. R kidney to -30 mmHg rNPT or no rNPT. HF was induced via cardiac tamponade (∼200 ml of pericardial 6% hydroxyethyl starch) and IV normal saline. Pericardial pressure was maintained at 20-22.5 mmHg. Results Prior to HF induction, rNPT increased urine output (UOP) & creatinine clearance (CrCl) compared to the control kidney during furosemide diuresis (p lt 0.001 for all, Figure). HF induction achieved the target hemodynamic profile with stable cardiac output & elevated filling pressures (Figure). UOP, sodium excretion, and CrCl decreased during HF (p lt 0.001 for all, Figure), but were higher consistently in rNPT kidney vs. control (p lt 0.05 for all, Figure). UOP (p=0.38) was the same in rNPT during HF as control prior to HF (Figure). Conclusions rNPT with the JuxtaFlow® system resulted in significantly increased diuresis, natriuresis, and creatinine clearance, both in the presence and absence of experimental HF. Notably, rNPT rescued the congested cardio-renal phenotype with equivalent diuresis and natriuresis during HF with rNPT as was observed in the non-HF period without rNPT. Additional research into the efficacy of the JuxtaFlow® system in human ADHF is warranted.

BACKGROUND: The estimated glomerular filtration rate (eGFR) from cystatin C (eGFRcys) is often considered a more accurate method to assess GFR compared with an eGFR from creatinine (eGFRcr) in the setting of heart failure (HF) and sarcopenia, because cystatin C is hypothesized to be less affected by muscle mass than creatinine. We evaluated (1) the association of muscle mass with cystatin C, (2) the accuracy of eGFRcys, and (3) the association of eGFRcys with mortality given muscle mass. METHODS AND RESULTS: We included 293 patients admitted with HF. Muscle mass was estimated with a validated creatinine excretion-based equation. Accuracy of eGFRcys and eGFRcr was compared with measured creatinine clearance. Cystatin C and creatinine were 31.7% and 59.9% higher per 14 kg higher muscle mass at multivariable analysis (both P < .001). At lower muscle mass, eGFRcys and eGFRcr overestimated the measured creatinine clearance. At higher muscle mass, eGFRcys underestimated the measured creatinine clearance, but eGFRcr did not. After adjusting for muscle mass, neither eGFRcys nor eGFRcr were associated with mortality (both P > .19). CONCLUSIONS: Cystatin C levels were associated with muscle mass in patients with HF, which could potentially decrease the accuracy of eGFRcys. In HF where aberrations in body composition are common, eGFRcys, like eGFRcr, may not provide accurate GFR estimations and results should be interpreted cautiously.

Sustainable fashion is clothing that we get substantial use of by never buying that’s less than contextually fabulous. Changing consumer consumption habits and technological intervention has created a world of fashion with short fashion cycles and planned obsolescence. The fast fashions and their ecological impact have drawn the attention of the researchers, with greater emphasis given to the intervention of the higher education institutions in sustainable development. Aligning to changing global requirements and readjusting to the region specific human resource needs arising out of ever-changing technology and industrial processes are some of the crucial contemporary issues that the higher education institutions have to learn to handle. Higher education institutions could no more remain as isolated centers of excellence, completely insulated from the socioeconomic mainstream. Being an epitome of knowledge creation and knowledge dissemination for the benefit of the societies, the institutions have to play a proactive role in identifying the growing impact of technological changes and unsustainable consumption patterns in different industries leading to environmental degradation. The institutes of higher education should aim at constant efforts to design and revitalize design courses with the aims of skill and competence inculcation along with the sensitivity for economic, social, and ecological sustainability. The collaborative efforts with different stakeholders play a prominent role in implementing sustainable practices. This paper as an attempt to address ecological sustainability emphasizes on the model involving the stakeholders and the institution of higher education in inculcating sustainable design practices among the budding designers.

Azoxystrobin, buprofezin, dinocap and hexaconazole are widely used in crop protection of mango from flowering to harvest. Residue assessment of these chemicals on mango fruits was done following treatments at the recommended and double doses as per good agricultural practices (GAP). Mango fruit and soil sample preparation was done by QuEChERS, and analysis was done using LC-MS/MS (liquid chromatography mass spectrometry). Using these techniques, the limit of detection (LOD) determined was 1.5 μg kg−1 and limit of quantification (LOQ) was 0.005 mg kg−1 for all analytes. The residue levels on mango initially were 0.265 and 0.55 mg kg−1 for azoxystrobin, 0.63 and 0.974 mg kg−1 for buprofezin, 0.635 and 0.98 mg kg−1 for dinocap and 0.203 and 0.35 mg kg−1 for hexaconazole from standard and double dose treatments, respectively. The dissipation rate of the pesticides on mango fruits was about the same except for azoxystrobin, which dissipated slowly compared with others. The half-life of degradation (DT50) of azoxystrobin was 10.4–12.1 days; buprofezin, 5.8–8.5 days; dinocap, 5.4–6.2 days; and hexaconazole, 4.4–6.1 days. The pre-harvest interval (PHI) based on European Union (EU) MRL (maximum residue limit) requirements were 1 day for azoxystrobin, 15 and 26 days for buprofezin, 27 and 34 days for dinocap, and 19 and 30 days for hexaconazole. The results of this study can be used to produce mango fruits safe for consumption and to meet the regulatory requirements for export of mango fruits from India.

Deceased donor kidneys with AKI are often discarded for fear of poor transplant outcomes. Donor biomarkers that predict post-transplant renal recovery could improve organ selection and reduce discard. We tested whether higher levels of donor urinary YKL-40, a repair phase protein, associate with improved recipient outcomes in a prospective cohort study involving deceased kidney donors from five organ procurement organizations. We measured urinary YKL-40 concentration in 1301 donors (111 had AKI, defined as doubling of serum creatinine) and ascertained outcomes in the corresponding 2435 recipients, 756 of whom experienced delayed graft function (DGF). Donors with AKI had higher urinary YKL-40 concentration (P

Women who carry a germline mutation in BRCA1 gene typically develop triple negative breast cancers (TNBC) and high grade serous ovarian cancers (HGSOC). Previously, we reported that wild type BRCA1 proteins, unlike the disease-associated mutant BRCA1 proteins to bind the sole sumo E2-conjugating enzyme Ubc9. In this study, we have used clinically relevant cell lines with known BRCA1 mutations and report the in-vivo association of BRCA1 and Ubc9 in normal mammary epithelial cells but not in BRCA1 mutant HGSOC and TNBC cells by immunofluorescence analysis. BRCA1-mutant HGSOC/TNBC cells and ovarian tumor tissues showed increased expression of Ubc9 compared to BRCA1 reconstituted HGSOC, normal mammary epithelial cells and matched normal ovarian tissues. Knockdown of Ubc9 expression resulted in decreased proliferation and migration of BRCA1 mutant TNBC and HGSOC cells. This is the first study demonstrating the functional link between BRCA1 mutation, high Ubc9 expression and increased migration of HGSOC and TNBC cells. High Ubc9 expression due to BRCA1 mutation may trigger an early growth and transformation advantage to normal breast and ovarian epithelial cells resulting in aggressive cancers. Future work will focus on studying whether Ubc9 expression could show a positive correlation with BRCA1 linked HGSOC and basal like TNBC phenotype.

Background and objectives Current measures for predicting renal functional decline in patients with type 2 diabetes with preserved renal function are unsatisfactory, and multiple markers assessing various biologic axes may improve prediction. We examined the association of four biomarker-to-creatinine ratio levels (monocyte chemotactic protein-1, IL-18, kidney injury molecule-1, and YKL-40) with renal outcome. Design, setting, participants, & measurements We used a nested case-control design in the Action to Control Cardiovascular Disease Trial by matching 190 participants with ≥40% sustained eGFR decline over the 5-year follow-up period to 190 participants with ≤10% eGFR decline in a 1:1 fashion on key characteristics (age within 5 years, sex, race, baseline albumin-to-creatinine ratio within 20 μ g/mg, and baseline eGFR within 10 ml/min per 1.73 m 2 ), with ≤10% decline. We used a Mesoscale Multiplex Platform and measured biomarkers in baseline and 24-month specimens, and we examined biomarker associations with outcome using conditional logistic regression. Results Baseline and 24-month levels of monocyte chemotactic protein-1-to-creatinine ratio levels were higher for cases versus controls. The highest quartile of baseline monocyte chemotactic protein-1-to-creatinine ratio had fivefold greater odds, and each log increment had 2.27-fold higher odds for outcome (odds ratio, 5.27; 95% confidence interval, 2.19 to 12.71 and odds ratio, 2.27; 95% confidence interval, 1.44 to 3.58, respectively). IL-18-to-creatinine ratio, kidney injury molecule-1-to-creatinine ratio, and YKL-40-to-creatinine ratio were not consistently associated with outcome. C statistic for traditional predictors of eGFR decline was 0.70, which improved significantly to 0.74 with monocyte chemotactic protein-1-to-creatinine ratio. Conclusions Urinary monocyte chemotactic protein-1-to-creatinine ratio concentrations were strongly associated with sustained renal decline in patients with type 2 diabetes with preserved renal function.

Introduction Congestion is the primary driver of acute decompensated heart failure (ADHF). Unfortunately, diuretic resistance and/or under dosing of diuretics is common, contributing to the large proportion of patients discharged with residual congestion. Given that natriuresis from a dose of IV loop diuretic is nearly complete by 6 h, diuretic titration should occur more frequently than once daily. As such, we designed an automated diuretic titration protocol that would allow nurses to titrate loop diuretic every 6 h. Hypothesis A nurse-driven diuretic titration protocol will provide rapid, effective, and safe titration of loop diuretics. Methods The Yale Diuretic Pathway (YDP) begins with providers ordering the YDP through an EMR order set and specifying (or accepting default) safety parameters such as change in blood pressure (default 0.5 mg/dL increase) and the starting diuretic dose (default 2 mg bumetanide). At 9 AM, the first dose of diuretic is administered, and 2 hours later a spot urine sample is collected, which is used to predict sodium excretion. Based on the YDP algorithm, every 6 h bumetanide is either doubled, administered at the same dose, or held to achieve the daily goal sodium output. The initial EMR order will provide the next AM's diuretic dose (based on the algorithm) thus giving the provider until 3pm to re-order the YDP if they want automated diuresis to continue. For our analysis, we compared data from 3 days before and 3 days after the start of the YDP. Results 161 hospitalized patients with ADHF received the YDP (age 69±12 years, eGFR 50±2 mL/min/1.73m2). Median time from admission to start of the YDP was 2 (1-4) days, and median dose of IV furosemide equivalents before YDP was 120 (80-140) mg. With the first YDP dose, suboptimal sodium output was displayed with a median calculated 6-hour sodium output of 37 (16-84) mmol. With subsequent doses, mean daily urine output (1817±90 mL pre-YDP vs. 3034±82 mL on-YDP), net fluid output (-1083±86 mL pre-YDP vs. -2071±89 mL on-YDP), and delta weight (pre-YDP -.31±.26 kg vs. -2.54±.34 kg on-YDP) improved substantially (p 0.5 mg/dL. Conclusion The YDP appears to allow fast, safe, and effective titration of loop with significantly improved decongestion following initiation. Further research to formally assess the YDP in randomized setting, and impact of this strategy on clinical outcomes, is warranted.

Introduction The majority of acute decompensated heart failure (ADHF) admissions are driven by congestion. Sodium is the primary pathophysiologic driver of volume retention, with water passively following. However, monitoring sodium output in routine clinical practice is challenging. We previously created a model, the natriuretic response prediction equation (NRPE), to predict total sodium excretion following an IV dose of loop diuretic. The NRPE requires only a spot urine sodium and creatinine obtained 2 hours following diuretic administration (Figure 1). The objective of this study was to externally validate the NRPE. Hypothesis NRPE will accurately predict 6 hour post loop diuretic sodium output. Methods A total of 638 urine collections from 409 patients hospitalized with ADHF undergoing intravenous loop diuretic therapy were included. Intensively supervised urine collections were performed, and urine spot samples were taken at 2 hours after loop diuretic administration. A poor natriuretic response was defined as a sodium output of 150 mmol within this 6-hour period. Results The median IV furosemide equivalent dose was 80 mg (40-160), resulting in a cumulative 6-hour sodium output of 85 mmol (50-143) and urine output of 960 mL (640-1410). Poor natriuretic response was observed in 25% of the urine collections, averaging a cumulative sodium output of 29±13 mmol. Suboptimal and excellent responses were seen in 57% and 21% of the visits. The NRPE accurately predicted poor, suboptimal, and excellent natriuretic response, with an AUC of 0.92, 0.90, and 0.90, respectively (p Conclusions The NRPE, using only a 2 hour post diuretic spot urine sample, is a rapid and highly accurate method to monitor natriuretic response in ADHF patients.

Aims We explored the relationship between inflammation, renalase an anti-inflammatory protein, and acute chest pain with coronary microvascular dysfunction (CMD). Methods and results We used cardiac Rb-82 PET/CT imaging to diagnose coronary artery disease (CAD/CALC) (defect or coronary calcification) and CMD (depressed coronary flow reserve without CAD) in patients with chest pain in an emergency department (ED). Blood samples were collected pre-imaging within 24 h of ED presentation and were analyzed for renalase and inflammatory markers including C-reactive protein, interleukins, interferon gamma, tumor necrosis factor, vascular endothelial growth factor, and metalloproteinases. Exclusions were age ≤30 years, myocardial infarction, hemodynamic instability, hypertensive crisis, heart failure or dialysis. Between 6/2014 and 11/2015, 80 patients undergoing PET/CT provided blood and were categorized as normal (18%), CAD/CALC (27%) and CMD (55%). Median renalase values were highest in patients with CMD (5503 ng/ml; IQR 3070) compared to patients with normal flows (4266 ng/ml; IQR 1503; p = 0.02) or CAD/CALC (4069 ng/ml IQR 1850; p = 0.004). CMD patients had similar median values for inflammatory markers as normal patients (p > 0.05). Renalase remained an independent predictor of CMD (OR 1.34; 95% CI = 1.1–1.7, per 1000 ng/ml) after adjustment for smoking, family history, obesity and Framingham risk score. In a model for CMD diagnosis with Framingham risk score, typical angina history and CRP, renalase improved discrimination from C-statistic = 0.60 (95% CI 0.47, 0.73) to 0.70 (95% CI, 0.59–0.82). Conclusion We found elevated renalase in response to ischemia from acute CMD. Its role as a biomarker needs validation in larger trials.

Rationale & objectiveRandom assignment to intensive blood pressure (BP) lowering (systolic BP

Background In acute decompensated heart failure, guidelines recommend increasing loop diuretic dose or adding a thiazide diuretic when diuresis is inadequate. We set out to determine the adverse events associated with a diuretic strategy relying on metolazone or high‐dose loop diuretics. Methods and Results Patients admitted to 3 hospitals using a common electronic medical record with a heart failure discharge diagnosis who received intravenous loop diuretics were studied in a propensity‐adjusted analysis of all‐cause mortality. Secondary outcomes included hyponatremia (sodium mE q/L), hypokalemia (potassium mE q/L) and worsening renal function (a ≥20% decrease in estimated glomerular filtration rate). Of 13 898 admissions, 1048 (7.5%) used adjuvant metolazone. Metolazone was strongly associated with hyponatremia, hypokalemia, and worsening renal function ( P P =0.01). High‐dose loop diuretics were associated with hypokalemia and hyponatremia ( P P P =0.52). Conclusions During acute decompensated heart failure, metolazone was independently associated with hypokalemia, hyponatremia, worsening renal function and increased mortality after controlling for the propensity to receive metolazone and baseline characteristics. However, under the same experimental conditions, high‐dose loop diuretics were not associated with hypokalemia, hyponatremia, or reduced survival. The current findings suggest that until randomized control trial data prove otherwise, uptitration of loop diuretics may be a preferred strategy over routine early addition of thiazide type diuretics when diuresis is inadequate.

The present study describes the uptake and distribution of fungicides, fluopyram, and tebuconazole in tomato and bell pepper plant tissues from the soil drench application of their combination product fluopyram17.7% + tebuconazole 17.7%. For extraction and cleanup of fluopyram, its metabolite fluopyram benzamide, and tebuconazole samples, the QuEChERS method was used in conjunction with LC-MS/MS. The limit of detection (LOD) and limit of quantification (LOQ) of the method determined were 1.5 μg kg−1 and 0.005 mg kg−1, respectively, and recoveries of all analytes from sample matrices remained within the acceptable range of 70–120%. Rapid uptake of the fungicides by tomato and bell pepper plants was observed from the first day onwards. In the tomato plant, the major part of the fungicides accumulated in the roots, whereas in bell pepper plant, it accumulated both in the roots and in the leaves. Accumulation of fluopyram and tebuconazole residues was lowest in tomato and bell pepper fruits which were much below their respective maximum residue limits (MRLs). The highest residue concentration of fluopyram and tebuconazole in tomato fruits was 0.060 and 0.009 mg kg−1; the corresponding values in bell pepper fruits were 0.080 and 0.013 mg kg−1. In field soil, fluopyram residues were 3.18–3.570 mg kg−1 initially which dissipated at the half-life of 36 days. Tebuconazole concentration was 1.57–1.892 mg kg−1 initially, and it dissipated at the half-life of 44.5–49.5 days. The major metabolite of fluopyram, fluopyram benzamide, was detected in plant tissues as well as in soil, and remained within 12% of the parent compound. The results of the study indicated that fluopyram and tebuconazole are less likely of entry into food chain through intake of tomato and bell pepper fruits if these crops are grown on soil contaminated with these fungicides.

Novel biomarkers are needed to predict kidney function decline in patients with type 2 diabetes, especially those with preserved glomerular filtration rate (GFR). There are limited data on the association of markers of endothelial dysfunction with longitudinal GFR decline. We used banked specimens from a nested case-control study in the Action to Control Cardiovascular Disease (ACCORD) trial (n=187 cases: 187 controls) and from a diverse contemporary cohort of type 2 diabetic patients from the Mount Sinai BioMe Biobank (n=871) to assess the association of plasma endostatin and kidney outcomes. We measured plasma endostatin at enrollment and examined its association with a composite kidney outcome of sustained 40% decline in estimated GFR or end-stage renal disease. Baseline plasma endostatin levels were higher in participants with the composite outcome. Each log2 increment in plasma endostatin was associated with approximately 2.5-fold higher risk of the kidney outcome (adjusted odds ratio [OR] 2.5; 95% confidence interval [CI] 1.5-4.3 in ACCORD and adjusted hazard ratio [HR] 2.6; 95% CI 1.8-3.8 in BioMe). Participants in the highest vs. lowest quartile of plasma endostatin had approximately four-fold higher risk for the kidney outcome (adjusted OR 3.6; 95% CI 1.8-7.3 in ACCORD and adjusted HR 4.4; 95% CI 2.3-8.5 in BioMe). The AUC for the kidney outcome improved from 0.74 to 0.77 in BioMe with the addition of endostatin to a base clinical model. Plasma endostatin was strongly associated with kidney outcomes in type 2 diabetics with preserved eGFR and improved risk discrimination over traditional predictors.

Introduction Low muscle mass, or sarcopenia, is commonly seen in patients with heart failure (HF). For any given level of renal function, patients with sarcopenia will have lower levels of serum creatinine because there is less muscle mass to produce creatinine. Thus, the use of creatinine to estimate glomerular filtration rate (GFR) is affected by sarcopenia. In contrast to creatinine, cystatin C is considered a better filtration marker to estimate GFR in the setting of sarcopenia because it not seclusively produced by muscle. However, it has not been demonstrated that serum cystatin C levels are independent of sarcopenia in patients with HF. Hypothesis Serum cystatin C levels will be minimally influenced by muscle mass in patients with heart failure. Methods Serum cystatin C and serum creatinine were measured in patients with decompensated heart failure. Strict timed urine collections were used to measure creatinine excretion rate. Muscle mass was estimated with a validated equation based on urine creatinine excretion (Heymsfield). Creatinine clearance was calculated and used as a surrogate for measured GFR. Results Out of the 295 patients analyzed (average age 65 ±14 years), 65% were male and 61% were obese. Baseline levels of serum creatinine were 1.5±0.6 mg/dL and cystatin C were 1.7±0.7 mg/L. In univariate analysis, serum cystatin C showed a negative correlation with muscle mass (rho -0.37, p Conclusion Serum cystatin C serum levels are strongly associated with muscle mass in patients with HF. This may lead to inaccuracies when cystatin C is used to estimate GFR.

Introduction Growth differentiation factor-15 (GDF-15) is a stress-responsive biomarker that is elevated in patients with heart failure (HF) and carries prognostic value. However, conditions other than HF can increase levels, making plasma concentration non-specific for HF. In diabetic patients, urinary GDF-15 has been associated with worse kidney function, but its role in HF remains unknown. Therefore, we sought to determine if urinary GDF-15 might provide unique cardio-renal information in patients with HF. Hypothesis Urinary GDF-15 will be associated with diuretic efficiency and survival, independently of plasma GDF-15. Methods GDF-15 was measured in 171 patients with heart failure treated with IV diuretics in the outpatient setting. Pre and post diuretic spot urinary GDF-15 (n=166) was measured using the Mesoscale Assay platform (MesoScale Diagnostics, Gaithersburg, MD, USA). Urinary GDF-15 was normalized to urine creatinine. Diuretic efficiency was defined as sodium excretion per doubling of loop diuretic dose. Results Plasma GDF-15 was weakly correlated with pre-diuretic urinary GDF-15 (r= 0.21, p=0.019) and modestly correlated with post-diuretic urinary GDF-15 (r=0.50, p Conclusion Plasma, but not urinary, GDF-15 was independently associated with diuretic efficiency and survival. This suggests that urinary GDF-15 does not provide specific cardio-renal information, likely because it is mainly filtrated from plasma rather than produced in the kidney.

Introduction Diuretic response is generally assessed using crude measures such as fluid or weight loss which are usually reported in a delayed manner (e.g. the change in weight from one day to the next). This in turn restricts clinicians’ ability to titrate diuretics. These established metrics have poor correlation with one another and they do not predict outcomes as well as cumulative sodium excretion. However, a 24h urine collection is difficult to perform even in a clinical trial, much less in routine clinical practice. It also does not address the lag time between diuretic administration and assessment of response. We previously reported proof of concept results on an equation to estimate sodium excretion based on a post-diuretic spot urine sample. Our current objective was to validate this equation in a real-world sample of patients undergoing IV diuretic therapy. Hypothesis Cumulative sodium output from a loop diuretic can be predicted using a spot urine sample. Methods The validation cohort consisted of 286 hospitalized patients receiving IV diuretics. Our equation is shown below (Figure). The validation cohort consisted of 286 hospitalized patients receiving IV diuretics. Urine collections were performed under intense supervision by a study coordinator. A spot urine was obtained at 1h, 2h post diuretic administration, and a cumulative 6h urine collection was used to determine total sodium. We used the 2h value for the equation. We defined a poor diuretic response as Results The predicted sodium equation had the best receiver operating characteristics (AUC = 0.92, 95% CI = 0.88 to 0.96, p Conclusions Our natriuretic response equation provides a faster and more accurate estimation of sodium excretion following a diuretic dose than either net fluid loss or weight change. This may aid in more rapid assessment of diuretic response and ultimately dose titration.

Introduction In the treatment of patients with acute decompensated heart failure (ADHF) estimation of the degree of volume overload is critical in guiding the goals of diuretic therapy. A “dry weight,” or the weight of a patient when they are euvolemic, is commonly used by clinicians to determine when to discontinue diuretic therapy during hospitalization. However, it is unclear how this dry weight relates to the actual weight loss achieved during hospitalization. Hypothesis Dry weight will have limited correlation with the ultimate weight loss achieved during hospitalization. Methods Patients hospitalized for ADHF with volume overload and receiving IV diuretics were enrolled. Each participant completed a clinical assessment survey that asked, “How many pounds of water weight are you above your dry weight?” We additionally extracted any dry weight that was documented in the electronic medical record (EMR) and the lowest documented weight in the EMR within the previous year. The primary comparison was to evaluate the correlation between the patients’ estimate above their dry weight and the degree of weight loss during ADHF hospitalization. Results 343 patients were enrolled and 246 (73%) were able to describe the amount of fluid above their dry weight, which was on average 15±18 lbs above ideal weight. The patient's estimate of their fluid excess correlated modestly with their actual weight loss during the admission (r= -0.38, P Conclusion Both the estimated and the EMR documented dry weight were only modestly correlated with the actual weight loss achieved during diuresis. Additional research is required to understand if the discrepancy between diuretic induced weight loss and “dry weight” is driven by inaccuracy in the “dry weight” or variability in the diuresis of these patients.

Background Fibroblast growth factor-23 (FGF-23) is a phosphaturic hormone with a primary role in the regulation of phosphate homeostasis. Recently, FGF-23 was shown to be a strong predictor of cardiovascular outcomes, and animal models have reported multiple non-phosphaturic, or off-target, effects of FGF-23. Some of the negative cardio-renal actions reported in the literature are adverse left ventricular remodeling, induction of inflammation, renal/cardiac fibrosis, and direct effects on renal sodium retention. The aim of this current investigation was to further explore the association between FGF-23 with various parameters of cardio-renal dysfunction. Hypothesis FGF-23 will be associated with cardio-renal parameters such as inflammation, neurohormonal activation, diuretic responsiveness, and survival. Methods We analyzed plasma FGF-23 levels in 199 outpatient heart failure (HF) patients who underwent diuretic administration followed by timed urine collections. Diuretic response was defined as the sodium output per doubling of the diuretic dose. Results Higher levels of FGF-23 tended to correlate with serum phosphate (r=0.21, p=0.09) but were not correlated with serum calcium (p=0.37). There were stronger correlations between FGF-23 and several parameters of cardio-renal dysfunction including lower eGFR (r=-0.42, p 0.3 for both). Higher levels of FGF-23 predicted worse diuretic responsiveness (r=-0.47, p Conclusion In patients with HF, plasma levels of FGF-23 were associated with multiple metrics of cardio-renal dysfunction, including a strong independent association with diuretic responsiveness and mortality. Additional research is warranted to understand if FGF-23 is a marker or mediator of cardio-renal dysfunction and if interventions to lower FGF-23 levels can improve outcomes.

Introduction There is interest in developing alternative therapies to loop diuretics for decongestion heart failure (HF). One approach is peritoneal dialysis (PD). However, PD requires large intraperitoneal volumes and delivers limited sodium removal due to the high concentration of sodium in standard PD solutions. Previously, we have demonstrated in normal and HF animal models that Direct Sodium Removal (DSR) with a sodium-free peritoneal solution is highly effective in removing large quantities of sodium and water, with low volumes of DSR solution. Hypothesis DSR will be safe, well tolerated, and result in substantially greater sodium removal than standard PD solution. Methods 10 patients underwent randomization and crossover to DSR solution (sodium free 10% dextrose) or standard PD solution (Dianeal 4.25% dextrose, Baxter), each separated by 1 week. One liter of either DSR solution or standard PD solution was infused into the peritoneum and left to dwell for 2 hours, with crossover to the alternate solution one week later. Vital signs, blood, and peritoneal fluid were obtained serially throughout the protocol. The primary endpoint was safety/tolerability defined as completion of the 2-hour dwell without significant discomfort or AE. The secondary efficacy endpoint was the difference in sodium removal between DSR solution and standard PD solution (NCT03801226; IND141103). Results DSR solution was well-tolerated and did not cause significant discomfort or adverse events. Individual safety parameters such as change in blood pressure, plasma potassium, bicarbonate, calcium and magnesium were similar between solutions (p>0.35 for all). There was a borderline significant 1 mmol/L decrease in serum sodium from baseline to 2 hours in the DSR group (p=0.05) but this resolved by 60 minutes after draining the solution (p=0.34). Plasma glucose increased with both DSR and standard PD solution (p Conclusion DSR was safe and well-tolerated in human subjects. Sodium removal with DSR is substantial and dramatically greater than what is achievable with standard PD solutions. Additional research evaluating the use of DSR as a method to prevent and treat hypervolemia in HF is warranted.

Class II invariant chain peptide (CLIP) expression has been demonstrated to play a pivotal role in the regulation of B cell function after nonspecific polyclonal expansion. Several studies have shown vitamin D3 helps regulate the immune response. We hypothesized that activated vitamin D3 suppresses CLIP expression on activated B-cells after nonspecific activation or priming of C57BL/6 mice with CpG. This study showed activated vitamin D3 actively reduced CLIP expression and decreased the number of CLIP+B-lymphocytes in a dose and formulation dependent fashion. Flow cytometry was used to analyze changes in mean fluorescent intensity (MFI) based on changes in concentration of CLIP on activated B-lymphocytes after treatment with the various formulations of vitamin D3. The human formulation of activated vitamin D (calcitriol) had the most dramatic reduction in CLIP density at an MFI of 257.3 [baseline of 701.1 (Pvalue = 0.01)]. Cholecalciferol and alfacalcidiol had no significant reduction in MFI at 667.7 and 743.0, respectively. Calcitriol seemed to best reduce CLIP overexpression in this ex vivo model. Bioactive vitamin D3 may be an effective compliment to other B cell suppression therapeutics to augment downregulation of nonspecific inflammation associated with many autoimmune disorders. Further study is necessary to confirm these findings.

Assessment of deceased-donor organ quality is integral to transplant allocation practices, but tools to more precisely measure donor kidney injury and better predict outcomes are needed. In this study, we assessed associations between injury biomarkers in deceased-donor urine and the following outcomes: donor AKI (stage 2 or greater), recipient delayed graft function (defined as dialysis in first week post-transplant), and recipient 6-month eGFR. We measured urinary concentrations of microalbumin, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) from 1304 deceased donors at organ procurement, among whom 112 (9%) had AKI. Each biomarker strongly associated with AKI in adjusted analyses. Among 2441 kidney transplant recipients, 31% experienced delayed graft function, and mean±SD 6-month eGFR was 55.7±23.5 ml/min per 1.73 m(2) In analyses adjusted for donor and recipient characteristics, higher donor urinary NGAL concentrations associated with recipient delayed graft function (highest versus lowest NGAL tertile relative risk, 1.21; 95% confidence interval, 1.02 to 1.43). Linear regression analyses of 6-month recipient renal function demonstrated that higher urinary NGAL and L-FABP concentrations associated with slightly lower 6-month eGFR only among recipients without delayed graft function. In summary, donor urine injury biomarkers strongly associate with donor AKI but provide limited value in predicting delayed graft function or early allograft function after transplant.

Background The incidence of anal carcinoma has increased over the last few decades especially in African Americans (AA) despite the use of highly active anti-retroviral therapy (HAART). Here, we retrospectively review oncologic outcomes of AA patients with anal squamous cell carcinoma (SCC) with and without HIV to further examine the cause of this trend. Materials and methods All adult AA patients diagnosed with anal SCC from 2000 to 2007 who met inclusion were examined. All patients were staged according to the American Joint Committee on Carcinoma (AJCC) sixth edition staging classification. Patients were divided into two cohorts: HIV (-) and HIV (+). Demographics, comorbidities, and oncologic outcomes were analyzed. Results Twenty-two AA patients with anal SCC were analyzed. Fifteen (68.%) were HIV (+) and seven (32%) were negative. Seventy-four percent of HIV (+) patients were on HAART therapy at the time of diagnosis. The HIV (+) cohort was significantly younger, mostly male, and had more comorbidities compared to the negative cohort. There was no difference in tumor, nodal or metastasis (TNM) stage for both cohorts. HIV (+) patients were more likely to receive non-operative therapy. The 5-year survival rate for HIV negative and positive patients was 57% and 58%, respectively. AJCC stage was the only factor predictive of survival after performing Cox hazard proportional regression analysis, HR: 1.96 (95% CI, 0.987 to 3.881). Conclusions In the HAART era, HIV (+) AA patients are at high risk of developing anal SCC. However, the prognosis of HIV (+) AA with anal SSC is similar to that of their HIV (-) counterparts. Carcinoma stage is the only factor predictive of survival.

Triple negative breast cancer (TNBC) is a heterogeneous disease and has a higher rate of recurrence and distant metastasis. African-American (AA) women have a higher frequency of BRCA1 mutations and TNBC compared to other populations. Basal-like tumors have a higher rate of brain, lung and distant nodal metastasis more than other TNBC subtypes, contributing to higher mortality rate. Our previous work suggested Ubc9, a SUMO E2-conjugating enzyme to induce proliferation and migration of BRCA1-incompetent TNBC cells and TNBC cell lines established from the pleural effusion metastasis of a woman with TNBC. To understand the downstream signaling axis involved in distant metastasis we have used clinically relevant BRCA1 mutant and lung metastatic TNBC cell lines and our results show deregulated expression of caveolin-1, VEGF and SIRT1 in these cells compared to normal mammary epithelial cells by immunofluorescence analysis. We observed SIRT1 to be induced by wild type BRCA1a and BRCA1a I26A mutant unlike the disease associated Ubc9 binding mutants in TNBC cells. Knock down of Ubc9 induced SIRT1 expression in TNBC and ER-α expression in breast cancer cells. This is the first report demonstrating a role for Ubc9 in repressing both SIRT1 and ER-α expression in BRCA1 associated TNBC cells. It also suggests that the BARD-dependent E3 Ubiquitin ligase and HR (homologous recombination) activity of BRCA1 may not be required for inducing SIRT1 expression. Our results suggest for the first time that in BRCA1 mutant TNBC Ubc9-mediated induction of VEGF, inhibition of caveolin-1, SIRT1 and ER-α expression as a novel molecular mechanism underlying TNBC EMT (epithelial mesenchymal transition) leading to lung metastasis with pleural effusion. Drugs that target Ubc9 to both induce SIRT1 and ER-α or using SIRT1 agonists in combination with chemotherapy can be used as a promising targeted therapeutic approach for treating basal-like metastatic BRCA1-linked TNBC thus reducing the mortality in patients with TNBC.

Biomarkers of diverse pathophysiologic mechanisms may improve risk stratification for incident or progressive diabetic kidney disease (DKD) in persons with type 2 diabetes. To evaluate such biomarkers, we performed a nested case-control study (n=190 cases of incident DKD and 190 matched controls) and a prospective cohort study (n=1156) using banked baseline plasma samples from participants of randomized, controlled trials of early (ACCORD) and advanced (VA NEPHRON-D) DKD. We assessed the association and discrimination obtained with baseline levels of plasma TNF receptor-1 (TNFR-1), TNFR-2, and kidney injury molecule-1 (KIM-1) for the outcomes of incident DKD (ACCORD) and progressive DKD (VA-NEPHRON-D). At baseline, median concentrations of TNFR-1, TNFR-2, and KIM-1 were roughly two-fold higher in the advanced DKD population (NEPHRON-D) than in the early DKD population (ACCORD). In both cohorts, patients who reached the renal outcome had higher baseline levels than those who did not reach the outcome. Associations between doubling in TNFR-1, TNFR-2, and KIM-1 levels and risk of the renal outcomes were significant for both cohorts. Inclusion of these biomarkers in clinical models increased the area under the curve (SEM) for predicting the renal outcome from 0.68 (0.02) to 0.75 (0.02) in NEPHRON-D. Systematic review of the literature illustrated high consistency in the association between these biomarkers of inflammation and renal outcomes in DKD. In conclusion, TNFR-1, TNFR-2, and KIM-1 independently associated with higher risk of eGFR decline in persons with early or advanced DKD. Moreover, addition of these biomarkers to clinical prognostic models significantly improved discrimination for the renal outcome.

TGF-β/Smads signaling plays a significant role in the regulation of growth of normal and prostate cancer cells. Smad proteins function as important mediators of intracellular signal transduction of transforming growth factor-β (TGF-β). TGF-β signaling pathway is known to regulate cell proliferation, differentiation, apoptosis and play a major role in some human diseases and cancers. Following their phosphorylation by TGF-β receptor-I, Receptor-regulated Smads (including Smad2 and Smad3 proteins) form a heteromeric complex with co-Smad (Smad4) and then translocate into the nucleus where they bind and regulate the expression of target genes. ERG (Ets Related Gene) belongs to the ETS family of transcriptional factors. Chromosomal rearrangement of TMPRSS2 gene and ERG gene has been found in majority of prostate cancers. Over-expression of full length or truncated ERG proteins have been shown to associate with a higher rate of recurrent and unfavorable prognosis of prostate cancer. In order to understand how ERG oncoprotein regulates TGF-β/Smads signaling pathway, we have studied the effect of ERG on TGF-β/Smad3 signaling pathway. In this study, we demonstrate that ERG oncoprotein physically interacts with Smad3 protein and stabilizes phospho-Smad3 protein and thereby enhance TGF-β/Smad3 signaling pathway in prostate cells. Thus, ERG oncoprotein plays an important role in prostate tumorigenesis by using a novel mechanism to activate TGF-β/Smad3 signaling pathway.

Background The primary therapeutic objective during the treatment of acute decompensated heart failure (ADHF) is relief from volume overload. This is achieved primarily through urinary losses of sodium and water from diuretics. Urine output is a primary source of data for monitoring and titrating therapy in these patients. To our knowledge, the prevalence and natural history of bladder dysfunction in patients with ADHF undergoing diuresis has not been described. Hypothesis Bladder dysfunction will be common among patients with ADHF. Methods Patients admitted to Yale New Haven hospital with worsening heart failure requiring IV diuresis were prospectively enrolled. After a forced void, bladder ultrasounds were conducted using a Verathon® BVI 3000 bladder scanner. Three values were taken for each patient and averaged. In a subset of these patients, an ambulatory outpatient follow-up bladder scan was performed. Results 283 patients were enrolled and underwent determination of post void residual (PVR) volume. The average PVR volume was 131 ± 169 ml. Only 41% of patients had a normal PVR ( 100 ml and 23% of the patients had a PVR greater than 200 ml, which meets criteria for acute urinary retention. Surprisingly, we did not find a significant difference in the PVR retention volume between men (138 ± 166 ml) and women (118 ± 173 ml; p=0.32). There was also no difference in the prevalence of a PVR greater than 200 ml between men and women (p=0.19). Similarly, age and diabetic status were not correlated with PVR (p=NS for both) and in patients with a PVR >200 ml both the age (65 ± 15 years vs. 64 ± 13 years, p=0.62) and odds of having diabetes (OR=1.1, p=0.78) were not different. A total of 106 patients returned for an ambulatory a median of 43 days after discharge and had a repeat determination of PVR. Notably, there was a significant improvement in PVR volume post discharge with a mean 58 ± 134 ml (p 200 ml while hospitalized but only 4.7% had a PVR>200 ml at the return visit. Conclusion Significant bladder dysfunction is highly prevalent in ADHF patients and was not associated with traditional causes for bladder dysfunction. This dysfunction was largely resolved upon outpatient follow-up. Additional research is needed to understand the cause and clinical implications of the high rate of bladder dysfunction in patients with ADHF.

Introduction Glomerular filtration rate (GFR) can be estimated using serum creatinine or cystatin C. At the population level, these equations predict GFR with similar accuracy but can give substantially different results at the level of an individual patient. These within-patient differences may be explained by factors such as inflammation, as cystatin C is associated with higher levels of established inflammatory markers. We sought to determine if the discordance between the two GFR estimates could be attributed to inflammation, and furthermore to examine if this information held prognostic value. Hypothesis Discordance of estimated GFR (eGFR) using creatinine vs. cystatin C will be affected by inflammation and patients with greater discordance will have worsened survival. Methods We analyzed an outpatient cohort of patients with chronic stable heart failure (n= 162). CKDEPI-Creatinine and CKDEPI-Cystatin C equations were used to estimate GFR. Discordance of eGFR was calculated as the ratio of eGFRcreatinine to eGFRcystatin. (values higher than 1 represent eGFRcreatinine > eGFRcystatin and lower than 1 represent eGFRcystatin > eGFRcreatinine). Results In the overall population eGFRcreatinine was 54±28mL/min/m2 and the eGFRcystatin was 43±25mL/min/m2, resulting in an average ratio of 1.3±0.4. There were, however, substantial differences in individual patients with the 10th percentile ratio at 0.9 and 90th percentile a ratio of 1.7. Notably, the ratio was correlated with plasma interleukin-6 (r= 0.24), C-reactive protein (r= 0.23), and ST2 (r= 0.26); p Conclusion The discordance of eGFR with creatinine and cystatin C was associated with markers of inflammation and holds powerful independent prognostic information. Additional study into the drivers of the discordance in GFR estimates by cystatin C and creatinine is warranted.