bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 135: Clinical Decision Making Utility of Stress Echocardiography in Contemporary Managed Patients with Suspected Coronary Artery Disease
Authors: Wild Nicholas C , Shultz John , Topliceanu Alexandru , Torosoff Mikhail 
Published: March 2022

Background:
We have investigated outcomes of contemporary management in patients undergoing stress echocardiography for evaluation of chest pain.

Methods:
Records of 294 consecutive patients who underwent a stress echocardiogram at a single tertiary care center were reviewed. Demographic, clinical data, and outcomes were collected. ANOVA, chi-square, and logistic regression analyses were used. Mean follow up length was 37 months. The study was approved by the IRB.

Results:
This study cohort included 46% women, with an average age of 61 +/- 10.6 years old; 20% were current smokers, with history of CAD in 26%, CHF in 4%, hypertension in 40%, diabetes in 14%, and peripheral vascular disease in 4%. Baseline medical treatment included beta blockers in 46% and ACE inhibitors in 24%. The majority (94%) of these patients underwent a dobutamine stress echocardiogram.

Fifty five of the 294 patients had ischemia during the test. Males were twice as likely to have ischemia during the stress test compared to females (24% vs. 12% p=0.009). There was a trend towards increased prevalence of ischemia in diabetics (26% vs. 17% p=0.175) and in smokers (24% vs. 17% p=0.262).
The presence of ischemia was associated with a 40% increase in mortality (14.5% vs. 10.5%) and an approximately 3-fold increase in MI (9.1% vs. 2.9% p=0.0679).
Patients with ischemia during stress testing were ten times more likely to have invasive cardiac evaluation and changes in medications compared to patients without ischemia during stress testing (41.5% vs. 4.1% p<0.001) or undergo invasive evaluation without a change in medications (24.5% vs. 3.3% p<0.001).
Invasive evaluation was not associated with a reduction in mortality (13.4% vs. 10.4% p=0.349). However, change in medications alone was associated with increased mortality (16.7% vs. 9.7% p=0.04).

Conclusions:
In the majority of contemporary managed patients with suspected coronary artery disease, stress testing is likely to have a normal result. When abnormal, it typically leads to invasive evaluation and/or medication changes. The small sample size of patients with ischemia in our study limits our ability to discern the effects of invasive evaluation and/or medicine changes on outcomes. Additional studies of this important subject are needed.
Abstract 205: Improving Door to Needle Time for IV Thrombolysis in Stroke
Authors: Johnson Brenda , Butler Jaime , Bojang Binta , Ortmann Melinda , Murtaza Umbreen , Lindauer Cathleen , Tolson Tina , Saheed Mustapha , Hill Peter , Urrutia Victor C 
Published: March 2022

Background:
Door to Needle Time (DNT) for IV tPA administration in acute stroke, has become an important quality metric. The rationale for this is based on evidence that earlier administration of IV tPA, improves patient outcomes.

Methods:
In 2010 we undertook a review of our hospital’s performance and process for administration of IV tPA for acute stroke. At the time, we were already using 7 elements of the AHA’s Target Stroke 10 best practices.

We created a pocket card for our Brain Attack team to record the time at which each task in the process was completed. We found that the greatest delay was in the time between the decision to treat and administration of tPA. The factors that contributed were insertion of a Foley catheter (part of our order set at the time), blood pressure control, and mixing tPA.
We instituted the 3 remaining Target Stroke best practices: activation of the Brain Attack team upon EMS advance hospital notification, mixing tPA ahead of time (right after CT scan), and prompt data feedback (case by case and aggregate).
We also eliminated the Foley catheter insertion requirement from the order set, instituted a streamlined blood pressure control guideline, created an incentive pin awarded for treatment under 60 minutes, started timely case by case review and feedback, and included DNT on our department’s safety dashboard.

Results:
From 2007 to 2010, there were 5/43 (11.6%) patients with a DNT less than 60 minutes (DNT<60), and the average yearly median DNT was 80 min.

After implementation:
In 2011, DNT<60 was 5/14 (35.7%) and median DNT was 67 min.

In 2012, DNT<60 was 11/28 (39%), DNT<45: 1/28 (3.6%),and median DNT was 67 min.
In 2013, DNT<60 was 16/39 (41%), DNT<45: 3/39 (7.7%), and median DNT was 68 min.
In 2014, DNT<60 was 19/39 (49%), DNT<45: 7/39 (18%), and median DNT was 61 min.
Adjusted (aDNT<60) results based on the Get With The Guidelines accepted medical reasons for exclusion of the metric (released in the Fall of 2012).
In 2013, aDNT<60 was 8/13 (61.5%) and median DNT was 55 min.
In 2014, aDNT<60 was 9/10 (90%) and median DNT was 56 min.

Conclusions:
Efforts to reduce DNT are effective and create incremental improvement over time. The organization required to lower door to needle time, results in an increase of the number of patients treated. This may be a result of the greater efficiency needed to achieve fast administration of IV tPA, which in turn, improves recognition of stroke patients and efficiency of decision making.

Our experience demonstrates that these gains are sustainable.
Abstract 347: Identification of Functional Limitations on Admission by Internal Medicine Resident Physicians
Authors: Milks M. Wesley , Wilson Farra , Dharod Ajay , Feiereisel Kirsten 
Published: March 2022

Low functional status on admission is associated with readmission, and functional limitations affect the disposition and prognosis of patients after hospital discharge. However, a formal assessment of functional impairment may not routinely be performed among general medical physicians. The aim of this intervention is that resident physicians better identify and document the baseline functional limitations of their patients in order to anticipate post-discharge resource needs more effectively.
A dedicated Functional History section was created in the admission history and physical (H&P) documentation template in the electronic medical record for use by house staff in one internal medicine residency program. Four questions were used to assess a patient’s baseline functional status, including the ability to complete activities of daily living (ADLs) and instrumental activities of daily living (iADLs), as well as ambulation status and pre-hospital residence. H&P documentation was sampled for patients admitted to resident teaching (intervention group) and hospital medicine (control group) services over 3 periods: 1) pre-intervention, 2) 1 week post-intervention, and 3) 10 weeks post-intervention. De-identified samples of 20 charts from each group were assessed by a blinded reviewer for each of the 3 time periods. H&Ps were scored for absence of (0 points), partial (1 point), or full (2 points) description of functional limitations in each of 3 categories: ADLs/iADLs, ambulation status, and pre-hospital residence, for a total score ranging from 0 to 6.
The average H&P functional limitation score (FLS) for patients admitted to the resident teaching services was (mean ± SEM) 0.45±0.27 prior to the intervention. The FLS increased significantly both at 1 and 10 weeks following the intervention, with values of 3.15±0.45 and 3.05±0.49, respectively (p < 0.001 for each, by 2-tailed Student’s t-test). The average FLS for hospital medicine patients was 0.20±0.12 in the pre-intervention period. Despite hospital medicine providers not receiving the intervention, there was a trend towards increased FLS that did not reach statistical significance for each subsequent period: 0.9±0.42 (p=0.12) at 1 week and 0.9±0.35 (p=0.07) at 10 weeks following the intervention.
Thoroughness of pre-admission functional limitation documentation was significantly increased by the addition of a distinct Functional History section to the H&P template used by residents at one academic medical center. Further study is needed to determine whether such documentation is associated with expedited discharge planning or improved readmission rate. A dedicated Functional History section in the H&P template may be considered by other programs that aim to increase awareness of patients’ pre-hospital functional limitations among their resident physicians.
Abstract 5: Heart Failure Patients Hospitalized with Bacterial Infections: A Nationwide Analysis of Concomitant Clostridium Difficile Infection Rates and In-Hospital Mortality
Authors: Mamic Petra , Heidenreich Paul A , Tennakoon Lakshika , Staudenmayer Kristan 
Published: March 2022

Heart failure (HF) patients have altered gut microbiota, as do patients who receive antibiotics for bacterial infections. Altered gut microbiota is associated with increased susceptibility to C. difficile infection (CDI). It is not known if HF patients hospitalized with bacterial infections experience CDI more frequently and whether CDI impacts their mortality.
We utilized Healthcare Cost and Utilization Project National Inpatient Sample data from 2010 to 2012 to determine the rate of CDI and associated in-hospital mortality for HF patients hospitalized with urinary tract infection (UTI), pneumonia (PNA) or sepsis. Univariate and multivariate analyses were performed. Unweighted data are presented.
We identified 868,401 HF patients hospitalized with UTI, PNA, or sepsis. There were 2,825,390 patients without HF hospitalized with the same infections. HF patients were on average older (75.4 vs 65.1 years, p<0.001) compared to patients without HF. In unadjusted analysis, HF patients hospitalized with UTI, PNA or sepsis had higher rates of CDI compared to patients without HF hospitalized with the same infections (UTI 3.9% vs 2.7%, PNA 2.9% vs 2.3%, sepsis 6.8% vs 5.3%; p<0.001 for all). Heart failure remained significantly associated with CDI (OR 1.2, 95% CI 1.18-1.23, p<0.001), even after controlling for patient demographics, insurance status, hospital characteristics, and presence of ischemic heart disease.
Heart failure patients hospitalized with UTI, PNA or sepsis and diagnosed with CDI had higher in-hospital mortality rates compared to HF patients hospitalized with UTI, PNA or sepsis who did not develop CDI (figure). CDI remained significantly associated with in-hospital mortality for HF patients hospitalized with bacterial infections (OR 2.0, 95% CI 1.9-2.1, p<0.001), even after controlling for the above variables.
Heart failure is associated with higher rates of CDI among patients hospitalized with common bacterial infections, even when adjusting for other known risks for CDI. Furthermore, within the HF population, CDI is associated with markedly higher in-hospital mortality. These findings suggest an opportunity to improve outcomes for HF patients through improved C. difficile screening and prophylaxis protocols.
Increased Epidermal Growth Factor Receptor Expression in Rat Aorta in Deoxycorticosterone Acetate-Salt Induced Hypertension/ATL>
Authors: Manteuffel Jacob J , Florian Jennifer A , Dorrance Anne N , Watts Stephanie W 
Published: March 2022

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Receptors and signal transduction
Epidermal growth factor (EGF) causes contraction in arteries from Deoxycorticosterone Acetate-Salt (DOCA) hypertensive rats but not in normotensive sham rats. We hypothesized that an increase in the number of EGF receptors (EGFR) in arteries from DOCA-salt rats enables the observed contraction to EGF to occur. All DOCA-salt rats had a systolic blood pressure (SBP) > 170 mm Hg, while all sham rats had a SBP < 135 mm Hg. Thoracic aorta were removed for measurement of isometric force, EGFR mRNA levels, and EGFR protein levels. EGF caused a significant contraction in endothelium-denuded aorta from DOCA-salt rats [(35 +/- 3% of maximal phenylephrine (PE, 10uM)-induced contraction)] as compared to aorta from sham rats (4+/-2%). EGFR tyrosine kinase specific inhibitors, 4,5-Dianilinophthalimide (10uM) and AG1478 (250 nM), reduced the contraction in aorta from DOCA-salt rats by 85 +/- 14% and 65+/- 10% respectively. The mRNA for EGFR in DOCA-salt aorta was increased 4.2 fold as compared to sham aorta. EGFR protein levels were examined using immunohistochemistry where specific binding was defined as binding which was quenched by a 10x concentration of neutralizing peptide. In 7 of 8 quantitative comparisons between aorta from DOCA-salt and sham rats, DOCA-salt aorta sections demonstrated greater specific binding than in sections of sham aorta. In the 7 positive comparisons, the difference in specific binding between DOCA-salt and sham sections ranged from 2.31 to 20.67 gray scale units (gsu) with an average of 9.18 gsu (figure). An increase in specific binding in aorta from DOCA-salt rats suggests the vessels have more EGFR that could facilitate the enhanced contractility to EGF in DOCA-salt aorta.
Abstract 195: Circadian Rhythm of Plasma and Urinary Angiotensinogen in Patients with Chronic Kidney Disease
Authors: Nishijima Yoko , Kobori Hiroyuki , Mizushige Tomoko , Hara Taiga , Nishiyama Akira , Kohno Masakazu 
Published: March 2022

Recent basic and clinical data demonstrated that the intrarenal renin-angiotensin system (RAS) plays an important role in the progression of chronic kidney disease (CKD). The urinary angiotensinogen (AGT) excretion rate could be a novel biomarker for the activity of the RAS in the kidney. We previously reported that the healthy volunteers do not have a circadian rhythm of AGT level in urine (Hypertension. 2011;57:e78) or in plasma (Hypertension. 2012;60:A399). However, the circadian rhythm of AGT level in urine and in plasma in patients with CKD has not been reported yet. Therefore, this study was performed to investigate the circadian rhythm of AGT level in urine and in plasma in patients with CKD.
We recruited 6 CKD patients with continuous proteinuria admitted to the Kagawa University Hospital from 06/2011 to 10/2011 for the purpose of diagnostic renal biopsy. Plasma samples were collected at 06:00, 12:00, and 18:00. Urine samples were collected at 06:00, 09:00, 12:00, and 18:00. Plasma renin activities (PRAs), plasma and urinary AGT concentrations, and urinary albumin (Alb) concentration were measured using commercially available kits. The urinary concentrations of AGT and Alb were normalized by the urinary concentration of creatinine (Cr) (UAGT/Cr and UAlb/Cr, respectively).
PRA (2.07 +/- 0.77 ng of angiotensin I/mL/hr at 06:00, 2.45 +/- 0.77 at 12:00, and 2.58 +/- 0.76 at 18:00, P = 0.8853) or plasma AGT (19.9 +/- 2.4 μg/mL at 06:00, 24.1 +/- 3.1 at 12:00, and 23.0 +/- 3.9 at 18:00, P = 0.6300) did not show a circadian rhythm. Moreover, UAlb/Cr (511 +/- 319 mg/g Cr at 06:00, 827 +/- 459 at 09:00, 1479 +/- 862 at 12:00, and 1370 +/- 818 at 18:00, P = 0.6964) or UAGT/Cr (54 +/- 22 μg/g Cr at 06:00, 119 +/- 41 at 09:00, 350 +/- 194 at 12:00, and 198 +/- 104 at 18:00, P = 0.3035) did not show a circadian rhythm.
In conclusion, in addition to healthy volunteers, patients with CKD do not have a circadian rhythm of AGT level in urine or in plasma.
Abstract 271: Does Obesity Alter the Normal Cardiovascular and Renal Adaptations of Pregnancy?
Authors: Cai Xiaochu , Kett Michelle M 
Published: March 2022

Obesity is associated with significant complications during pregnancy, including hypertensive disorders of pregnancy, and increased risk of cardiovascular and renal disease later in life. Surprisingly, we know little about the impact of obesity on the cardiovascular and renal adaptations that occur during a normal pregnancy. The aim of present study was to determine the adaptations that occur in mean arterial pressure (MAP), heart rate (HR) and renal function across pregnancy in a mouse model of diet-induced obesity.
At 4wks of age, female C57BL6J mice were place on a control (Cont; 16% fat, 3.85 kCal/g; n=8) or high fat (HF; 43% fat, 4.54 kCal/g; n=7) diet for 10 weeks and glucose tolerance tests (GTT) performed. Baseline MAP and HR (radio-telemetry), and 24hr urinary albumin excretion (n=3-5/gp) were measured. Mice were then mated, and MAP and HR measured throughout gestation with 24hr albumin excretion reassessed at gestational day (GA) 13.
After 10 wks of the diet, body weight of HF mice was 40% greater than Cont mice (33.2±1.8 vs 23.6±0.6g; P<0.001). Both groups of mice had similar fasting blood glucose. The obese mice were, however, glucose intolerant compared to Cont mice (725±60 vs 467±64, Area Under the Curve; P<0.05), had elevated basal MAP (105.2±2.1 vs 99.3±1.6mmHg; P<0.05), HR (556±13 vs 492±17bpm; P<0.05) and were albuminuric (4.53±0.62 vs 2.42±0.42μg/24h; P<0.05). Following mating, MAP (Pdiet<0.01) and HR (Pdiet<0.05) of obese mice remained elevated over Cont mice throughout pregnancy. However the adaptations of MAP and HR in obese mice over pregnancy, including the dip in MAP at GA9, were consistent in timing and magnitude with Cont mice. Pregnancy led to a significant increase in 24hr albumin excretion at GA13 (Ppreg<0.001), however this effect was exacerbated in obese mice (9.95±0.88 vs 4.03±1.1μg/24h; PpregXdiet <0.01).
Obesity results in higher MAP and HR before pregnancy and both remain elevated throughout pregnancy without altering the normal adaptations of MAP and HR during pregnancy. Importantly, pregnancy exacerbates albuminuria in obese females suggesting that obese pregnancy might increase the risk of renal complications during pregnancy and lead to renal disease in the long-term.
Abstract 38: Exosomes Secreted From Human Renal Proximal Tubule Cells Can Transfer Their Contents to Proximal Tubule, Distal Tubule and Collecting Duct Cells
Authors: Gildea John J , Reyes Camellia M , Bigler Wang Dora , Pettigrew Abigail C , Carlson Julia M , Felder Robin A 
Published: March 2022

Exosomes are 50-90 nm extracellular membrane particles that may mediate trans-cellular communication between cells and tissues. We have previously found that urinary exosomes contain miRNA that are biomarkers for salt sensitivity and inverse salt sensitivity of blood pressure. We also found that urinary exosomes contain dopamine 1 receptor and G protein-coupled receptor kinase type 4. We have also shown that exosomes can transfer between cultured human renal proximal tubule cells (RPTC). Here, we further explored RPTC-to-RPTC exosomal transfer using 5 RPTC lines containing exosomes that were fluorescently labelled with either exosomal-specific marker CD63-EGFP or CD9-mCherry. Transfer between RPTCs was confirmed by co-culturing CD63-EGFP and CD9-mCherry stable RPTC clones and performing live confocal microscopy. Dual color time-lapse videos reveal unique cellular secretion and uptake patterns for exosomes and eventual accumulation into the multi-vesicular body.
We hypothesized that proximal tubule-derived exosomes could also be taken up by the distal tubule (DT). Five DT and 3 collecting duct (CD) cell lines were isolated and immortalized by infecting with hTert-containing lentiviral particles. DT cells were isolated from human kidney by collagenase digestion and biotinylated lectin or immuno-magnetic affinity separation (using dolichos biflorus agglutinin (DBA) or anti-Tamm-Horsfall protein antibody). CD cells were similarly isolated with anti-L1CAM antibody. Using sterile-filtered cell culture supernatant from 3 different CD9-mCherry RPTC lines, all 5 DT cell lines showed exosome transfer at 24 hours as measured by microplate fluorometry (10,406 ± 1132 SEM RFU above background, p<0.0001, n=30). Similarly, all 3 CD cell lines showed significant exosome transfer (8773 ± 1558 SEM RFU, p<0.0001, n=18). CD63-EGFP exosomes from 2RPTC lines also transferred to all of the DT cell lines (1713 ± 1131 RFU above background, p<0.0001, n=30) and CD cell lines (1007 ± 315 RFU, p<0.01, n=18).
In conclusion, intra-nephron cellular exosomal transfer is demonstrated in RPTCs and between RPTCs and distal tubule and collecting duct cells. This proximal to distal nephron transfer may represent a new trans-cellular communication within the human kidney.
Abstract 381: Placental Growth Factor Controls Splenic Immunity to Drive Hypertension
Authors: Carnevale Daniela , Pallante Fabio , Fardella Valentina , Iacobucci Roberta , Fardella Stefania , De Lucia Massimiliano , Lembo Giuseppe 
Published: March 2022

Although several therapeutical strategies have been developed against the main components involved in the regulation of blood pressure (BP), an optimum control in some hypertensive patients is still flawed, suggesting that mechanisms still unidentified, sustain the increase of BP. Interestingly, an emerging area of investigation revealed that adaptive immunity is a central player of hypertension, since mice devoid of T lymphocytes were protected from AngII-induced hypertension. However, how hypertensive stimuli, like AngII, can afford this, still represents a fascinating enigma, challenging the search for molecular players, capable to bridge vascular responses to immune cells and probably orchestrating the still unveiled role of immune system in hypertension.
Here we demonstrate an unprecedented splenic immune pathway driven by Placental Growth Factor (PlGF), an “angiogenic cytokine” acting as a bridge between the cardiovascular and immune system during onset of hypertension. We found that the typical hypertensive response induced by chronic AngII infusion, was completely prevented in mice with genetic deletion of PlGF, as well as the typical end organ damage induced by hypertension and immune cells infiltration in target organs. To determine whether the involvement of PlGF in immune system activation and T cells infiltration during AngII-induced hypertension had a causal role or was merely a consequence of the failure in BP raise, we analyzed both vessels and kidney, early after AngII infusion, i.e. before BP increase. Strikingly, PlGF absence protected from early infiltration of both CD4+ and CD8+ T cells. More interesting, we unveil that the spleen is indispensable in the genesis of hypertension by releasing PlGF, that orchestrates the T cell response, necessary for blood pressure raising. In particular, we show that splenic PlGF acts as a negative checkpoint of a tissue protein of inflammation (Timp3), a repressor of T cell costimulation axis, thus allowing T cell activation and egression from spleen. Basically, this breakthrough in a key immune pathway determining blood pressure elevation, holds a great translational promise for patients with refractory disease and multiple complications.