bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 268: Using Lean Methodology to Reduce Variation in Care of Acute Coronary Syndrome Patients
Authors: Kmetic Andrew , Fradet Guy , Hamman Ronnalea , Laberge Carol , Galte Carol 
Published: July 2021

Background:
Regional variation in the utilization of health services is a well-documented phenomenon in health care with numerous studies reporting substantial and unexplained variations in coronary revascularization. In the Canadian province of British Columbia (BC), five cardiac centers provide coronary revascularization services. In 2011 Cardiac Services BC (CSBC) undertook a study that identified substantial regional variation in coronary revascularization that could not be explained by patient characteristics or risk factors. Following this initial project, CSBC launched an initiative to help better understand the regional variations and possibly devise and implement strategies to reduce them.

Methods:
Using Lean methodology, we are mapping the key processes of care for ACS patients across BC (initially excluding emergent STEMI and cardiogenic shock) at each cardiac centre. The ACS patient journey will be mapped from admission to discharge through several key decision points that determine whether they will continue through to diagnostic catheterization and revascularization or to be medically managed alone.

The key decision points are:
1. Decision to refer to diagnostic catheterization and subsequent transfer if necessary.
2. Decision to continue to a revascularization procedure (PCI or CABG) after diagnostic catheterization.
The map will summarized these key decision points using multiple sources of data:
1. Flow and patient volumes into and out of each of these decision
2. Times between decision points and key care processes
3. Clinical influencers (ex: standard orders, best practice, established patterns of referral, and consultations) and non-clinical influencers (ex: resource capacity, transportation) that are considered at each decision point (process mapping and interview data).

Discussion:
BC is attempting to reduce unexplained variation in coronary revascularization using the Lean methodology to take a systematic approach to the analysis of the process of ACS care across the province. Involving physicians and point of care staff in the detailed mapping process has proven to be a significant step in engaging key stakeholders in the project by allowing input into the process of describing the factors affecting variation of practice at each site. The next step is to convene provincially to determine where to improve standardized practice in order to improve patient outcomes at key points along the value stream.
Abstract 615: Renal Sympathetic Denervation: A Comparison Of Irrigated And Non-irrigated Radiofrequency Ablation In A Porcine Model
Authors: Koruth Jacob S , Dukkipati Srinivaz , Miller Marc A , Neuzil Petr , D'avila Andre , Reddy Vivek Y 
Published: July 2021

Introduction:
Renal artery sympathetic denervation using radiofrequency (RF) energy has recently been shown to reduce blood pressure in patients with hypertension. However arterial damage is required to achieve denervation, which has unknown long term consequences. Alternative techniques of denervation that minimize arterial wall damage are therefore preferable. We compared the ability of irrigated RF vs. non-irrigated RF to ablate the nerve fibers with respect to the degree of arterial wall sparing in an in vivo model.

METHODS:
Percutaneous femoral arterial access was obtained in 14 adult

swine and renal angiography was performed to assess for stenosis at baseline and at time of sacrifice . Irrigated (3.5mm tip/30cc) and non-irrigated RF (3.5, 4mm and 2mm tips) energy was delivered bilaterally using custom catheters. All animals were then recovered and survived
for 30-90 days. Renal cortical tissue was collected from bilateral kidneys for norepinephrine levels prior to sacrifice.

Results:
There was no significant interval renal artery stenosis. Arteries were sequentially sectioned, processed, cut at 4-6 μm and stained with hematoxylin&eosin and movat pentachrome. Arterial medial injury (percentage depth) and nerve injury were then scored on a incremental scale of 0-4. Medial injury was significantly less in the irrigated group vs. non-irrigated group (1.15vs 2.2 p<0.05). Nerve injury on the other hand was similar in both groups (1.75 vs. 1.24,p=0.24). Norepinephrine levels were obtained in 11/14 animals. In the irrigated and non-irrigated arms there was a 67% and 53% reduction of norepinephrine levels compared to that of controls.

Conclusions:
Irrigated RF ablation is an efficacious and feasible means to achieve renal denervation. Although medial injury occurred in both groups, irrigated RF demonstrates a lower degree of medial injury for similar levels of nerve injury when compared to non-irrigated RF.
Abstract 377: Unravelling the Association between Blood Pressure and Insulin-like Growth Factor-1
Authors: Schutte Aletta E , Mels Catharina M , Smith Wayne , Schutte Rudolph , Malan Leone , Huisman Hugo W , Van Rooyen Johannes M , Fourie Catharina M , Malan Nico T , Kruger Ruan , Conti Elena 
Published: July 2021

Conflicting reports exist on the relationship between systolic BP (SBP) and insulin-like growth factor-1 (IGF-1). Where positive associations are observed in patients with acromegaly, others find a negative association or no relationship. The versatile functions of IGF-1 as a growth factor (vasoprotective versus arterial and cardiac remodelling), the interplay with other hormones as well as IGF-1 resistance phenomena as those shown in chronic renal failure, are mostly regarded as confounding this relationship and thereby resulting in conflicting results. We aimed to review and compare regression coefficients for the association between SBP and total IGF-1 as reported in the literature and two studies from the general population.
We searched the literature for studies reporting the mentioned regression coefficients. We also included data from the SAfrEIC and SABPA studies in South Africa (total N=912) including African and Caucasian men and women, aged 20-70 yrs.
When plotting the regression coefficients from 13 studies with 20 data points against IGF-1 concentrations, we found a significant association between the regression coefficients and IGF-1 concentration (r=0.80; p<0.001). The slope intercepted the y-axis at IGF-1 concentration of 223.5 ± 14.4 ng/mL. Studies with mean IGF-1 at this range reported weak non-significant regression coefficients (typically young healthy men). Studies including acromegalic patients or adolescents reported significant positive associations, with negative associations for those with compromised cardiovascular function.
Our findings suggest that the regression coefficient for the SBP and IGF-1 relationship is dependent on the IGF-1 concentration. Positive associations are observed in situations with overtly high IGF-1 concentrations as those found in acromegaly or conditions of IGF-1 resistance, and beneficial negative relationships seen in those with low-normal IGF-1 and with compromised vascular function such as type 2 diabetes and hypertension. Our results suggest that the complex interplay between IGF-1 and other vasoactive hormones (e.g. growth hormone, insulin, cortisol and adipokines) or the development of a vascular resistance to IGF-1, may hamper the vasoprotective functions of IGF-1.
Abstract 512: Drugs in the Elderly: Threats and Opportunities
Authors: Wehling Martin 
Published: July 2021

Taking 10 and more drugs is unpredictable and may cause more harm than good, given that up to 100,000 medication-related deaths in the United States annually.
An early attempt to improve drug safety in the aged population was the establishment of criteria for drugs to avoid by Beers in 1997.
The evidence for the effectiveness of the Beers list is not compelling.. There should also be a positive labelling of drugs that are indispensable in elderly people as data on morbidity, mortality, and safety are available or emerging for this particular group. There is increasing clinical evidence for beneficial action of, for example, antihypertensive drugs (e.g., Hypertension in the Very Elderly Trial) in elderly people.
Drugs should be labelled taking into consideration their usefulness for elderly people (Table 1) This classification would be an extension of the Beers approach into the positive listing of valuable drugs. This seems necessary as overtreatment and undertreatment are both typical problems of the aged population. Undertreatment, for example, relates to the poor control of arterial hypertension elderly people and may leave more than half of the patients un- or undertreated.
The FORTA classification for antihypertensive drugs as an example is as follows: diuretics B, betablockers B, renin-angiotensin-system blockers A, long acting dihydropyridine calcium channel blockers (CCB) A, CCBs, verapamil type D, spironolactone C, alphablockers C, clonidine D, minoxidil D.
The typical use of the scheme would address general practitioners struggling with polypharmacy. They would then synthesize the recommendations into a rank order of drugs that they could use to cut the list short.
Abstract 541: Blood Pressure at 20 Weeks’ Gestation is Predictive of Hypertensive Disease in Pregnancy and is Independently Associated With 5-year Hypertensive Morbidity Post Delivery
Authors: Mito Asako , Arata Naoko , Qiu Dongmei , Sakamoto Naoko , Oya Yukihiro , Matsuoka Ryu , Sekizawa Akihiko , Ichihara Atsuhiro , Murashima Atsuko , Kitagawa Michihiro 
Published: July 2021

[Background]
Hypertensive disease in pregnancy (HDP) is associated with a risk of subsequent hypertension. However the influence of normotensive blood pressure (BP) during pregnancy on future BP is not clear.

[Purpose]
To investigate the association between BP measurements at their lowest levels in pregnancy, 20 weeks’ gestation (20 wks BP), and the risk of hypertension both ①during pregnancy and ②5 years after delivery.

[Methods]
A total of 1542 women who delivered singletons at the National Center for Child Health and Development and Showa University Hospital were recruited between 2003 and 2007. They were invited to undergo a physical examination 5 years after delivery. Following exclusions (see below), 772 women completed the analysis. The influence of 20 wks BP on HDP and 5-year hypertension was assessed by multiple logistic regression analysis. The odds ratio for HDP was adjusted by age at delivery, pre-pregnancy BMI, familial history of hypertension (FH), previous history of HDP and parity (Model 1) and that for subsequent hypertension was adjusted by existence of HDP in index pregnancy, age, BMI, FH and renal disease (Model 2).

[Criteria]
HDP was defined as sBP ≥ 140 mm Hg or dBP ≥ 90 mm Hg from 20 weeks’ gestation which remits by 12 weeks postpartum w/o proteinuria.

Hypertension at physical examination was defined as average sBP ≥ 140 mm Hg or average dBP ≥ 90 mm Hg or treatment with antihypertensive agents.

[Exclusion criteria]
Chronic hypertension / Women who were pregnant and nursing when the physical examination was done

[Results]
There were 26 HDP cases and 25 cases of 5-year hypertension (HDP: 6, normotensive control: 19).

① The odds ratio (95%CI) for HDP (adjusted by Model 1) is sBP:1.11 (for every 1 mmHg rise) (1.05~1.17), dBP:1.15(1.06~1.24) and BP category defined by the American Heart Association : 5.82 (for every 1 category increase)(2.15~15.76). A positive correlation between 20 wks BP and HDP risk was observed.
② The odds ratio for subsequent hypertension (adjusted by Model 2) is sBP: 1.06 (1.01-1.11), dBP:1.15(1.06-1.24) and BP category: 4.50(1.64-12.33).

20 wks BP is associated with subsequent hypertension,
independent of HDP
.

[Conclusions]
20 wks BP may predict both HDP and subsequent hypertension 5 years post delivery.
Abstract 561: The ex vivo RAS-Fingerprint - A Novel Approach for the Biochemical Chatracterization of the Renin-Angiotensin-System in Clinical Samples
Authors: Poglitsch Marko , Haschke Manuel , Stoller Andrea , Schwager Cornelia , Domenig Oliver , van Oyen Dunja 
Published: July 2021

Angiotensin concentrations are affected by multiple molecular components including receptors and enzymes which might be either dissolved in plasma or attached to blood cells or endothelial surfaces throughout the body, giving rise to a concentration determining local enzymatic environment. This environment substantially changes during blood collection leading to a rapid and fundamental shift in angiotensin peptide levels. Therefore, a clearly defined and properly controlled sample stabilization procedure is essential for the accurate measurement of in vivo angiotensin peptide levels.
Surprisingly, standard samples collected by anti-coagulation with heparin can be used for analyzing the human RAS under well-defined steady-state conditions, allowing RAS-Fingerprint based conclusions about the activities of circulating enzymes involved in angiotensin metabolism. The mass spectrometry based measurements of in vivo RAS-Fingerprints (immediate sample stabilization) or heparin plasma derived ex vivo RAS-Fingerprints in plasma or whole blood provide unique insights into the physiology of the human RAS. RAS-Fingerprinting provides an integrated view about the activity of the enzymes involved in angiotensin metabolism in a plasma sample and therefore represents a powerful tool for characterization of the patient specific “Biochemical Hardware”, which determines angiotensin peptide levels in vivo.
The assay is compatible with undiluted plasma and whole blood and can be further applied to long-term stored frozen plasma samples. The utilization of RAS-Fingerprinting in clinical studies will substantially enhance our understanding of the human RAS and could lead to the development of personalized approaches for the treatment and prevention of cardiovascular diseases in the near future.
Abstract 649: Endothelial-derived Sphingolipids Preserve Systemic Vascular Function And Blood Pressure
Authors: Cantalupo Anna , Zhang Yi , Obinata Hideru , Galvain Syvain , Jiang Xiang-Cheng , Giordano Frank , Hla Timothy , Di Lorenzo Annarita 
Published: July 2021

Endothelial dysfunction is a critical event in many cardiovascular diseases including hypertension. Although lipid signaling is implicated in endothelial dysfunction and cardiovascular diseases, specific molecular mechanisms are poorly understood. Here we report a novel regulation of endothelial sphingolipid synthesis by Nogo-B, membrane protein of the endoplasmic reticulum that modulates local sphingolipid production with direct effects on vascular function and blood pressure. Nogo-B inhibits serine palmitoyltransferase, rate-limiting enzyme of the sphingolipid de novo synthesis, controlling endothelial sphingosine 1-phosphate production and its autocrine G-protein-coupled receptor-dependent signaling actions. Mice lacking Nogo-B are hypotensive (90.1±1.6 vs. 119.9±2.6 mmHg WT mice), resistant to Ang-II (500ng/Kg/min)-induced hypertension (150.4±2.5 vs. 108.4±1.5 mmHg, compared to WT mice, 24 days after AngII infusion), and preserve endothelial function and nitric oxide release. Pharmacological inhibition of serine palmitoyltransferase with myriocin in mice that lack Nogo-B reinstated endothelial dysfunction and Ang-II-induced hypertension (143.9±1.5 vs. 90.1±1.6 mmHg, myriocin vs. vehicle treated Nogo-A/B-/- mice).
Our study identifies Nogo-B as a key inhibitor of local sphingolipid synthesis and indicates that autocrine sphingolipids signaling within the endothelium are critical for vascular function and blood pressure homeostasis.
Abstract 016: Profound and Sustained Amplification of Circulating ACE2 Activity Does Not Protect Diabetic Mice from Kidney Disease
Authors: Wysocki Jan , Ye Minghao , Khattab Ahmed M , Kanwar Yashpal , Osborn Mark , Batlle Daniel 
Published: July 2021

ACE2 is a monocarboxypeptidase that by converting AngII to Ang1-7 should down-regulate the renin-angiotensin system and therefore provide a means to therapeutically target diabetic kidney disease, a condition where the kidney RAS is overactive. Previous work indicated that soluble human recombinant (r)ACE2 administration for 4 weeks attenuated kidney injury in diabetic Akita mice. Whether such effect of rACE2 can be confirmed and attributed to augmented ACE2 activity is uncertain because chronic use of human rACE2 in mice induces immunogenicity and the development of antibodies that neutralize serum ACE2 activity.
To examine the effect of chronic amplification of circulating ACE2 on kidney injury caused by STZ-induced diabetes and to circumvent the immunogenicity arising from xenogeneic ACE2, ACE2 of mouse origin was administered to mice using either daily i.p. injections (1 mg/kg) of mrACE2 for 4 weeks or after 20 weeks of ACE2 mini-circle (MC) (10-30ug/mouse) administration. MC provides a form of gene delivery that is resistant to gene silencing and, in addition, greatly optimizes long-term in vivo overexpression of proteins of interest. ACE2MC resulted in a profound and sustained increase in serum ACE2 activity (2.4±0.3 vs. 497±135 RFU/ul/hr, p<0.01) but kidney ACE2 activity was unchanged (17.4±1.3 vs. 19.0±0.8 RFU/ug prot/hr). mACE2-treated mice injected with STZ developed diabetes similar to sham mice injected with STZ. Systolic BP was not different between non-diabetic mice, sham STZ-mice, and STZ-mice receiving mACE2 by either i.p. mrACE2 or ACE2MC. Urinary albumin was similarly increased in sham STZ-mice and in STZ-mice receiving mACE2. Glomerular mesangial score and glomerular cellularity were both increased to a similar extent in sham STZ-mice and in STZ-mice with mACE2 administration, as compared to non-diabetic controls.
In conclusion, profound and long-term augmentation of ACE2 activity confined to the circulation is not sufficient to attenuate glomerular pathology and albuminuria in STZ-induced diabetic kidney disease probably because of lack of kidney delivery of ACE2. Strategies to achieve over-expression of ACE2 at the kidney level are needed to demonstrate a beneficial effect of this enzyme on diabetic kidney disease.
Abstract P089: Inhibition of AT1-AAs by Direct Binding Reduces Blood Pressure and Natural Killer Cell Activation in Response to Placental Ischemia of Pregnancy; Emphasizing the Importance of Novel Drug Development in the Treatment of Preeclampsia
Authors: Campbell Nathan , Cunningham Mark W , Cornelius Denise C , LaMarca Babbette 
Published: July 2021

Preeclampsia (PE), hypertension with proteinuria during pregnancy, is associated with activating antibodies to the angiotensin II receptor (AT1-AA) and activation of cytolytic natural killer (NK) cells. The objective of our study was to determine if AT1-AA inhibition inhibits cytolytic NK cell activation in the reduced uterine perfusion pressure (RUPP) rat model of PE. We utilized a novel approach of specific epitope binding to inhibit AT1-AAs: AT1-AA inhibitory peptide (2ug/ml saline) was infused via miniosmotic pumps into RUPP rats beginning on day 14 of gestation. On day 19 of gestation, blood pressure (MAP) was measured and flow cytometry was performed to measure total and cytolytic NK cells in renal and placental tissues from all groups of rats.
MAP significantly increased from 87.1±6.2 in NP (n=5) to 125±2.3 in RUPP (n=6). Inhibition of AT1-AA by direct binding attenuated the hypertensive response to 74.9±19.02 mmHg in RUPP + AT1-AA inhibitor (n=3). Total renal NK cells measured at 10.21±3.69% in NP, 24.19±6.63% in RUPP, and 14.25±7.52% in RUPP + AT1-AA inhibitor. Total placental NK cells were 6.87±2.84% in NP (n=6), 27.62±10.97% in RUPP (N=6), and 6.35±3.90% in RUPP + AT1-AA inhibitor (N=5) rats. Importantly, activated cytolytic placental NK cells were significantly increased in NP (0.44±.24%) compared to RUPP (11.87±2.06%), and was blunted after epitope binding of AT1-AA in RUPP + AT1-AA inhibitor (2.33±1.02%, p<.0001 vs RUPP).
These studies indicate that AT1-AA inhibition improves maternal blood pressure and attenuates cytolytic activation of NK cells in response to placental ischemia, thereby emphasizing the importance of drug discovery for AT1-AA inhibition to improve pregnancy outcomes in preeclamptic patients.
Abstract P130: A Map of SPRINT’s Data-free Zone
Authors: Laffin Luke J , Besser Stephanie A , Alenghat Francis J 
Published: July 2021

120 mmHg is an optimal SBP goal according to the SPRINT trial. However, certain inclusion and exclusion criteria cloud its broad applicability. It is critical to understand which patients are well represented and reasonable candidates for intensive BP goals. Using only trial inclusion and exclusion criteria diminishes the fact that subjects are unevenly distributed across these criteria. A patient may fit study constraints, yet be poorly represented. Conversely, a patient may be excluded based on a parameter, and declared an inhabitant of a "data-free zone," yet in other respects resemble the trial population.
We defined and mapped the "data-rich, data-limited, and data -free zones" of SPRINT based on subjects’ baseline characteristics and not on inclusion and exclusion criteria. For each participant (n=9245), a z-score was computed for 6 variables: age, SBP, glucose, non-HDL-C, creatinine, and BMI. Standardized coefficients from multivariable logistic regression, based on SPRINT’s primary end-point, were used to weigh variables. Summary Scores (SS) were generated for each subject to scale with the Euclidean distance of participants from the theoretical "average patient" in six dimensional space.
A SS of 0.56 represents the 90th percentile and 0.74 represents the 97.5th. These were chosen as borders between the data-rich, data-limited, and data-free zones. SS were then calculated for 2007-14 NHANES participants with age >35, SBP≥130, and HbA1c<7. The NHANES population mapped onto SPRINT data zones shows a landscape of applicability by race and sex (Figure).
Defining data zones based on patient characteristics holds promise to refine the applicability of trial results.
Abstract P389: Post-traumatic Stress-induced Sensitization of Angiotensin II Hypertension is Reversed by Blockade of Angiotensin-converting Enzyme or Tumor Necrosis Factor-alpha
Authors: Xue Baojian , Yu Yang , Wei Shun-Guang , Beltz Terry G , Guo Fang , Felder Robert B , Johnson Alan K 
Published: July 2021

Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrated that post-traumatic stress disorder (PTSD) sensitizes angiotensin (ANG) II-elicited hypertension, which was associated with upregulation of central renin-angiotensin system (RAS) components and proinflammatory cytokines (PICs). The present study investigated whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor-α (TNF-α) prior to PTSD blocks sensitization of ANG II-elicited hypertensive response. The resident-intruder paradigm was used to model PTSD. Each intruder rat (male Sprague-Dawley) was pretreated with ACE inhibitor (captopril, 0.5 mg/Ml) or with TNF-α inhibitor (pentoxifylline, PTX, 100 mg/kg/day) in the drinking water for two weeks and then exposed to a different resident (male Long-Evans) for 2 hours on three days with each session separated by 1 day. Beginning 3 days after the last exposure, the intruder (PTSD) rats and unstressed control rats received a subcutaneous infusion of ANG II (120 ng/kg/min) for 2 weeks. The PTSD rats had a significantly enhanced hypertensive response to the ANG II infusion and an upregulation of mRNA expression of RAS and PIC components and of a microglial marker in the lamina terminalis (LT) when compared to control rats. Both the sensitized hypertensive response and enhanced gene expression were blocked by pre-treatment with either ACE inhibitor or TNF-α antagonist. These results suggest
that upregulation of the brain RAS and PICs produced by a severe stress contribute to PTSD-induced sensitization of the hypertensive response to ANG II.