bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atrial functional mitral regurgitation
Authors: Hoit Brian D. 
Published: July 2020

Purpose of review
To review the prevalence and prognosis of atrial functional mitral regurgitation (AFMR), the distinctive echocardiographic and mechanistic findings, and the therapeutic implications of this newly described disorder.

Recent findings
Initial studies identified an association between atrial fibrillation, mitral annular dilation, and significant mitral regurgitation despite a normal mitral valve and left ventricle. Accumulating data suggest that AFMR is not rare and may have a prognosis as poor as functional MR associated with LV remodeling. Echocardiography has played an important role in understanding the unique pathophysiology of AFMR, and proposed mechanisms include not only atrial remodeling, but structural and functional abnormalities of the LV (HFpEF shares a common pathophysiology) and insufficient leaflet growth. Timely rhythm control of atrial fibrillation and strategies that reduce diastolic pressure, left atrial and mitral annular enlargement, and that favorably affect mitral leaflet adaptation, are promising preventive and treatment options that warrant clinical study.

Summary
Functional mitral regurgitation may be atrial in origin and should be considered in patients with (particularly long-standing) atrial fibrillation and in those with HFpEF.
Opportunities for improved cardiovascular disease prevention in oncology patients
Authors: Bravo-Jaimes Katia , Marcellon Roselande , Varanitskaya Liubou , Kim Peter Y. , Iliescu Cezar , Gilchrist Susan C. , Baldassarre Lauren A. , Manisty Charlotte , Ghosh Arjun K. , Guha Avirup , Lopez-Mattei Juan C. 
Published: July 2020

Purpose of review
Cancer patients often have cardiovascular risk factors at the time of cancer diagnosis, which are known to increase the risk of cardiotoxicity. Cancer survivors have significantly higher cardiovascular risk. Current cardiovascular disease prevention guidelines are based on studies that largely excluded these patients. We reviewed recent data regarding cardiovascular disease prevention in this population.

Recent findings
Nonpharmacologic therapies aiming to reduce ‘lifestyle toxicity’ produced by cancer treatments have demonstrated potential to decrease the incidence of adverse outcomes. Exercise before, during and after cancer treatment not only promotes higher quality of life and cardiorespiratory fitness but also reduces adverse cardiovascular outcomes. Lipid and cardiometabolic disease management is paramount but predominantly based on data that excludes these populations of cancer patients and survivors.

Summary
A comprehensive approach including medical evaluation, prescriptive exercise, cardiac risk factor modification, education, counseling, pharmacologic and behavioral interventions are needed in cancer patients. These interventions constitute the core of cardio-oncology rehabilitation programs, which if implemented appropriately may help reduce cardiovascular events in this population. Knowledge gaps in these areas are starting to be addressed by ongoing clinical trials.
Treatment-resistant hypertension in the hemodialysis population: a 44-h ambulatory blood pressure monitoring-based study
Authors: Mallamaci Francesca , Torino Claudia , Sarafidis Pantelis , Ekart Robert , Loutradis Charalampos , Siamopoulos Kostas , Del Giudice Antonio , Aucella Filippo , Morosetti Massimo , Raptis Vasilios , Bikos Athanasios , Papagianni Aikaterini , Balafa Olga , Pappas Efthymios , Tripepi Rocco , Marino Carmela , Tripepi Giovanni , Ferro Charles , Malyszko Jolanta , Dekker Friedo W. , Jager Kitty J. , London Gérard M. , Zoccali Carmine 
Published: July 2020

Background:
Uncontrolled hypertension notwithstanding the use of at least three drugs or hypertension controlled with at least four drugs, the widely accepted definition of treatment-resistant hypertension (TRH), is considered as a common problem in the hemodialysis population. However, to date there is no estimate of the prevalence of this condition in hemodialysis patients.

Method:
We estimated the prevalence of TRH by 44-h ambulatory BP monitoring (ABPM) in 506 hemodialysis patients in 10 renal units in Europe included in the registry of the European Renal and Cardiovascular Medicine (EURECAm,), a working group of the European Association, European Dialysis and Transplantation Association (ERA EDTA). In a sub-group of 114 patients, we tested the relationship between fluid overload (Body Composition monitor) and TRH.

Results:
The prevalence of hypertension with 44-h ABPM criteria was estimated at 85.6% (434 out of 506 patients). Of these, 296 (58%) patients were classified as uncontrolled hypertensive patients by 44-h ABPM criteria (≥130/80 mmHg). Two hundred and thirteen patients had uncontrolled hypertension while on treatment with less than three drugs and 210 patients were normotensive while on drug therapy (n = 138) or off drug treatment (n = 72). The prevalence of TRH was 24% (93 among 386 treated hypertensive patients). The prevalence of predialysis fluid overload was 33% among TRH patients, 34% in uncontrolled hypertensive patients and 26% in normotensive patients. The vast majority (67%) of hemodialysis patients with TRH had no fluid overload.

Conclusion:
TRH occurs in about one in four treated hypertensive patients on hemodialysis. Fluid overload per se only in part explains TRH and the 67% of these patients show no fluid overload.
Air pollution-associated blood pressure may be modified by diet among children in Guangzhou, China
Authors: Zhang Jingshu , Cai Li , Gui Zhaohuan , Wang Suhan , Zeng Xia , Lai Lijuan , Lv Yajie , Tan Kaiyun , Wang Hui , Huang Cunrui , Chen Yajun 
Published: July 2020

Objectives:
To assess the associations between long-term air pollution exposure and blood pressure in children, and to explore the modifying effects of diet on prehypertension and hypertension.

Methods:
We evaluated 7225 primary school children aged 6–12 years from Guangzhou, China, in 2017. The blood pressure was measured objectively. The individual 1-year average concentration of particles with an aerodynamic diameter of 2.5 μm or less or 10 μm or less (PM2.5, PM10), sulfur dioxide (SO2), and ozone (O3) before each blood pressure measurement were calculated by inverse distance weighting interpolation according to each home address. Generalized linear mixed-effects models were used to examine the health effects and potential effect modifications by diet factors after adjusting for covariates.

Results:
The results showed that the estimated increase in mean SBP was 0.92 mmHg (95% CI 0.05–1.79) per interquartile range increase in O3. An interquartile range increase in the 1-year mean of SO2 and O3 was associated with odds ratios of 1.26 (95% CI 1.04–1.52) and 1.20 (95% CI 1.06–1.35) for prehypertension, respectively. In addition, an interquartile range increase in PM2.5, SO2, and O3 exposure was positively associated with hypertension, with odds ratios of 1.33 (95% CI 1.11–1.61), 1.70 (95% CI 1.33–2.16), and 1.48 (95% CI 1.20–1.83), respectively. Stronger effect estimates between PM2.5, SO2, and O3 concentration on prehypertension were exhibited among subgroups of children with a higher intake of sugar-sweetened beverages.

Conclusion:
Long-term exposure to PM2.5, SO2, and O3 were associated with higher blood pressure levels in children, and dietary intake might modify these associations.
Sustained Elevation of Intraocular Pressure After Administration of Intravitreal Anti-Vascular Endothelial Growth Factor Agents in Patients With and Without Pseudoexfoliation Syndrome
Authors: Ucgul Ahmet Y. , Aktas Zeynep , Ozgur Armagan , Cubuk Mehmet O. , Hasanreisoglu Murat , Ozdek Sengul , Gurelik Gokhan 
Published: July 2020

Précis:
Intravitreal anti-vascular endothelial growth factor therapy resulted in sustained elevation of intraocular pressure (IOP) in 18.6% of patients with coexisting age-related macular degeneration and pseudoexfoliation (PXF) syndrome. The development of sustained elevation of IOP after ~19 injections reflected the cumulative effect of anti-vascular endothelial growth factor injections on IOP.

Purpose:
The purpose of this study was to compare the long-term effect of intravitreal ranibizumab (IVR) and intravitreal bevacizumab (IVB) therapies on IOP in patients with and without PXF syndrome.

Design:
This was a retrospective comparative study.

Patients and Methods:
Data from 412 eyes of 206 patients diagnosed with unilateral neovascular age-related macular degeneration, treated with IVR or IVB, and followed-up for at least 6 months, were retrospectively reviewed. Seventy treated and 70 untreated fellow eyes of 70 patients with bilateral PXF syndrome, and 136 treated and 136 untreated fellow eyes of 136 patients without PXF syndrome were included in this study. Demographic information, clinical findings, total number of IVR and IVB injections, and IOP values at each visit were recorded. Sustained elevation of IOP (SE-IOP) was defined as either an IOP >21 mm Hg or a ≥5 mm Hg increase in IOP from baseline for at least 2 consecutive visits. Baseline and final IOP values in each group were compared using the paired sample t test, and IOP changes in the groups were compared using split-plot analysis of variance. Multivariate logistic regression analysis was used to evaluate the influence of variables on the development of SE-IOP.

Results:
The mean (±SD) age of the patients was 77.53±3.78 years (range, 70 to 83 y), and the mean follow-up was 28.50±16.51 months (range, 6 to 58 mo). The mean number of injections was 15.56±8.01 (range, 5 to 36). The mean baseline and final IOP in treated eyes were 14.82±3.08 and 16.50±3.11 mm Hg, respectively (P<0.001). A higher incidence of SE-IOP and higher final IOP values were observed in PXF-positive eyes receiving IVB compared with the other groups. Seven of the patients required antiglaucomatous treatment. Multivariate logistic regression analysis revealed an increased odds ratio (4.90; P=0.016) of SE-IOP in PXF-positive eyes compared with PXF-negative eyes.

Conclusion:
IVB therapy may cause greater increases in IOP in patients with PXF syndrome. The co-accumulation of PXF material and bevacizumab particles on the trabecular meshwork should be further investigated.
Performance of radiography and single-photon emission computed tomography/computed tomography in painful total hip arthroplasty and impact on arthroplasty survival
Authors: Schuldt Anna , Lehnick Dirk , Agten Christoph A. , Beck Martin , Kist Markus , Bhure Ujwal , del Sol Pérez Lago María , Strobel Klaus 
Published: July 2020

Purpose
To investigate the performance of radiography and single-photon emission computed tomography/computed tomography (SPECT/CT) in painful hip arthroplasty regarding loosening and arthroplasty survival.

Methods
Radiography and SPECT/CT reports of 249 painful hip arthroplasties of 191 patients were reviewed. Positive imaging was defined if loosening, infection, and polyethylene wear were found, indicating the need for arthroplasty exchange. Median time from radiograph to operation or last follow-up was 41.3 months (range 0.3–118.4 months). In 67 patients, the performance of radiographs and SPECT/CT regarding loosening was compared with an intraoperative reference standard. The time point of arthroplasty exchange was compared with imaging diagnosis and evaluated with Kaplan–Meier curves.

Results
Exchange of cup, shaft, or both was performed in 76 of 249 arthroplasties. Main diagnoses on SPECT/CT were loosening (n = 94), infection (n = 5), and polyethylene wear (n = 15). In total, 104 patients were SPECT/CT positive compared to 84 patients on radiography. Five-year survival of arthroplasties for radiograph positive and negative arthroplasties was 41.5%/83.4% and 39.3%/90.7% for SPECT/CT, respectively. Prognostic impact regarding arthroplasty exchange was highest in radiograph and SPECT/CT concordant positive patients (hazard ratio 19.7 as compared to radiograph and SPECT/CT negative patients). Sensitivity and specificity in 67 operated patients regarding shaft loosening were 59.4%/80.0% with radiography, 90.6%/68.6% with SPECT/CT (P = 0.002 for sensitivity and P = 0.29 for specificity), and for cup loosening 47.4%/89.6% with radiography and 63.2%/85.4% with SPECT/CT (P = 0.51, respectively, P = 0.63).

Conclusion
In patients with painful hip arthroplasty, positive radiography, and SPECT/CT are associated with poorer arthroplasty survival. Performance regarding loosening is slightly better with SPECT/CT.
Microcrystalline Cellulose and Crospovidone Identified in Placentas With Vaginal Misoprostol Use
Authors: Butler Daniel C. , Presnell Susan Erin , Bruner Evelyn , Page Tyrish , Cuff Ryan , Phillips Angelina 
Published: July 2020

Abstract
Misoprostol is a prostaglandin analog commonly used to induce termination of pregnancy. Clandestine home terminations complicate forensic fetal autopsy when a history of misoprostol use is withheld and the gross and histologic findings are sparse, as is often the case. One hundred thirty-two placentas with no vaginal misoprostol use, low-dose misoprostol use, and high-dose misoprostol use were reviewed for the presence, volume, and locations of microcrystalline cellulose and crospovidone, common tablet fillers in misoprostol tablets. Microcrystalline cellulose and/or crospovidone was identified in 0 (0%) of 88 cases with no vaginal administration or low-dose vaginal administration and 29 (66%) of 44 placentas with high-dose vaginal administration. When identified, microcrystalline cellulose and/or crospovidone is most commonly present on the maternal surfaces of the extraplacental membranes. The presence of microcrystalline cellulose and/or crospovidone was associated with smaller placental weight (Mann-Whitney U, P = 0.019). These fillers have a reasonable sensitivity for high-dose vaginal tablet use and are very specific. Although they are not diagnostic for misoprostol administration, they provide a finding that may prompt additional investigation into the nature of the vaginal tablet administered and the circumstances surrounding birth.
Adverse Biology in Adenocarcinoma of the Esophagus and Esophagogastric Junction Impacts Survival and Response to Neoadjuvant Therapy Independent of Anatomic Subtype
Authors: Donlon Noel E. , Elliott Jessie A. , Donohoe Claire L. , Murphy Conor F. , Nugent Tim , Moran Brendan , King Sinead , Ravi Narayanasamy , Reynolds John V. 
Published: July 2020

Objective:
The aim of this study was to propose and test a novel adverse pathology classification in AEG.

Background:
Recent scientific advances show genomic and molecular concordance across all AEG types, suggesting a rationale for a biologic classification. We tested a 3-dimension adverse pathology classification across the entire junction and per Siewert anatomic subtype.

Methods:
Of 1625 patients with AEG, 650 underwent radical surgery, 55% post-neoadjuvant therapy (NeoT). Adverse features defined a priori were poor differentiation (PD), lymphatic invasion (LI), vascular invasion (VI), and perineural invasion (PN), with 3 groupings: 0 (no adverse feature), 1 to 2, and 3 to 4. Multivariable logistic and Cox proportional hazards regression were applied.

Results:
For adverse pathology, 31%, 46%, and 23% had 0, 1 to 2, and 3 to 4, respectively. Fifty percent of cases were AEG I, 25% AEG II, and 25% AEG III. Median survival was not reached, 49 and 17 months for 0, 1 to 2, and 3 to 4 adverse pathology, respectively (P < 0.001), and 76, 51, and 34 months for AEG I, II, and III, respectively (P < 0.001); AEG I was significantly (P< 0.001) associated with lower c (y)pT and c (y)pN stages, and LI, VI, PN, and PD (poor vs other). The pathology model was significant for survival along with (y)pT and (y)pN, and predicted response to chemotherapy and chemoradiation irrespective of anatomic subtype (P < 0.001).

Conclusion:
A novel classification using standard pathology as proxy for poor biology is associated with survival and response to therapy. This effect is observed across the entire AEG spectrum, highlighting how biology should be aligned with anatomy in the modern paradigm of AEG management and design of clinical trials.
Patient-derived Organoid Pharmacotyping is a Clinically Tractable Strategy for Precision Medicine in Pancreatic Cancer
Authors: Seppälä Toni T. , Zimmerman Jacquelyn W. , Sereni Elisabetta , Plenker Dennis , Suri Reecha , Rozich Noah , Blair Alex , Thomas Dwayne L. , Teinor Jonathan , Javed Ammar , Patel Hardik , Cameron John L. , Burns William R. , He Jin , Tuveson David A. , Jaffee Elizabeth M. , Eshleman James , Szabolcs Annamaria , Ryan David P. , Ting David T. , Wolfgang Christopher L. , Burkhart Richard A. 
Published: July 2020

Objective:
PDAC patients who undergo surgical resection and receive effective chemotherapy have the best chance of long-term survival. Unfortunately, we lack predictive biomarkers to guide optimal systemic treatment. Ex-vivo generation of PDO for pharmacotyping may serve as predictive biomarkers in PDAC. The goal of the current study was to demonstrate the clinical feasibility of a PDO-guided precision medicine framework of care.

Methods:
PDO cultures were established from surgical specimens and endoscopic biopsies, expanded in Matrigel, and used for high-throughput drug testing (pharmacotyping). Efficacy of standard-of-care chemotherapeutics was assessed by measuring cell viability after drug exposure.

Results:
A framework for rapid pharmacotyping of PDOs was established across a multi-institutional consortium of academic medical centers. Specimens obtained remotely and shipped to a central biorepository maintain viability and allowed generation of PDOs with 77% success. Early cultures maintain the clonal heterogeneity seen in PDAC with similar phenotypes (cystic–solid). Late cultures exhibit a dominant clone with a pharmacotyping profile similar to early passages. The biomass required for accurate pharmacotyping can be minimized by leveraging a high-throughput technology. Twenty-nine cultures were pharmacotyped to derive a population distribution of chemotherapeutic sensitivity at our center. Pharmacotyping rapidly-expanded PDOs was completed in a median of 48 (range 18–102) days.

Conclusions:
Rapid development of PDOs from patients undergoing surgery for PDAC is eminently feasible within the perioperative recovery period, enabling the potential for pharmacotyping to guide postoperative adjuvant chemotherapeutic selection. Studies validating PDOs as a promising predictive biomarker are ongoing.
Angioembolization in intra-abdominal solid organ injury: Does delay in angioembolization affect outcomes?
Authors: Chehab Mohamad , Afaneh Amer , Bible Letitia , Castanon Lourdes , Hanna Kamil , Ditillo Michael , Khurrum Muhammad , Asmar Samer , Joseph Bellal 
Published: July 2020

INTRODUCTION
Angioembolization (AE) is an integral component in multidisciplinary algorithms for achieving hemostasis in patients with trauma. The American College of Surgeons Committee on Trauma recommends that interventional radiologists be available within 30 minutes to perform emergent AE. However, the impact of the timing of AE on patient outcomes is still not well known. We hypothesized that a delay in AE would be associated with increased mortality and higher blood transfusion requirements in patients with blunt intra-abdominal solid organ injury.

METHODS
A 4-year (2013–2016) retrospective review of the ACS Trauma Quality Improvement Program database was performed. We included adult patients (age, ≥18 years) with blunt intra-abdominal solid organ injury who underwent AE within 4 hours of hospital admission. Patients who underwent operative intervention before AE were excluded. The primary outcome was 24-hour mortality. The secondary outcome was blood product transfusions. Patients were grouped into four 1-hour intervals according to their time from admission to AE. Multivariate regression analysis was performed to accommodate patient differences.

RESULTS
We analyzed 1,009,922 trauma patients, of which 924 (1 hour, 76; 1–2 hours, 224; 2–3 hours, 350; 3–4 hours, 274) were deemed eligible. The mean ± SD age was 44 ± 19 years, and 66% were male. The mean ± SD time to AE was 144 ± 54 minutes, and 92% of patients underwent AE more than 1 hour after admission. Overall 24-hour mortality was 5.2%. On univariate analysis, patients receiving earlier AE had decreased 24-hour mortality (p = 0.016), but no decrease in blood products transfused. On regression analysis, every hour delay in AE was significantly associated with increased 24-hour mortality (p < 0.05).

CONCLUSION
Delayed AE for hemorrhagic control in blunt trauma patients with an intra-abdominal solid organ injury is associated with increased 24-hour mortality. Trauma centers should ensure timeliness of interventional radiologist availability to prevent a delay in vital AE, and it should be a focus of quality improvement projects.

LEVEL OF EVIDENCE
Prognostic, level III.
Resuscitative endovascular balloon occlusion of the aorta for thoracic trauma in the setting of platelet dysfunction: A translational swine study
Authors: Glaser Jacob J. , Neidert Leslie E. , Morgan Clifford G. , Brenner Megan , Stigall Kyle S. , Cardin Sylvain 
Published: July 2020

BACKGROUND
In patients with noncompressible torso hemorrhage, antiplatelet medications may lead to worse outcomes. Resuscitative endovascular balloon occlusion of the aorta (REBOA) may potentially stabilize these patients, but currently, major thoracic bleeding is a contraindication. The goal of this study was to determine if REBOA use for shock with major thoracic bleeding has worse outcomes in the setting of platelet dysfunction (PD).

METHODS
Forty-one male Yorkshire swine (60–80 kg) underwent a 30% hemorrhage and then were randomized to three thoracic injuries, with and without zone 1 REBOA occlusion: pulmonary parenchymal injury (PI), thoracic venous injury (VI), or subclavian artery injury (AI). All animals were given aspirin to produce PD. Following hemorrhage, thoracic injuries were induced (T0) and allowed to bleed freely. Resuscitative endovascular balloon occlusion of the aorta groups had zone 1 occlusion, with deflation at T30. All groups received whole blood resuscitation at T30 and were euthanized at T90. Survival, total blood loss, hemodynamics, and arterial blood gas parameters were analyzed.

RESULTS
The PD-VI-REBOA group had 87.5% survival where PD-VI survival was 28.6%. No difference in survival was seen in the PI or AI groups. The PD-VI-REBOA group had total blood loss of 575.0 ± 339.1 mL, which was less than the PD-VI group (1,086.0 ± 532.1 mL). There was no difference in total thoracic blood loss in the PI and AI groups with the addition of REBOA. All groups showed an equivalent decrease in HCO3 and base excess and increase in lactate at the end of the 30-minute prehospital phase.

CONCLUSION
In this study, zone 1 REBOA improved survival and decreased blood loss with major VI, where no differences were seen in parenchymal and subclavian artery injuries. For thoracic bleeding without surgical capability, outcomes may be improved with REBOA, and these findings challenge current guidelines stating the contraindication of REBOA use in this setting.