bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac Resynchronization Therapy With or Without Defibrillation: A Long-Standing Debate
Authors: Golzio Pier Giorgio , Bocchino Pier Paolo , Bissolino Arianna , Angelini Filippo , Gravinese Carol , Frea Simone
Published: March 2021

Cardiac resynchronization therapy (CRT) was shown to improve cardiac function, reduce heart failure hospitalizations, improve quality of life and prolong survival in patients with severe left ventricular dysfunction and intraventricular conduction disturbances, mainly left bundle branch block, on optimal medical therapy with ACE-inhibitors, β-blockers and mineralocorticoid receptor antagonists up-titrated to maximum tolerated evidence-based doses. CRT can be achieved by means of pacemaker systems (CRT-P) or devices with defibrillation capabilities (CRT-D). CRT-Ds offer an undoubted advantage in the prevention of arrhythmic death, but such an advantage may be of lesser degree in nonischemic heart failure etiologies. Moreover, the higher CRT-D hardware complexity compared to CRT-P may predispose to device/lead malfunctions and the higher current drainage may cause a shorter battery duration with consequent premature replacements and the well-known incremental complications. In a period of financial constraints, also device costs should be carefully evaluated, with recent reports suggesting that CRT-Ps may be favored over CRT-Ds in patients with nonischemic cardiomyopathy and no prior history of cardiac arrhythmias from a cost-effectiveness point of view. The choice between a CRT-P or a CRT-D device should be patient-tailored whenever straightforward defibrillator indications are not present. The Goldenberg score may facilitate this decision-making process in ambiguous settings. Age, comorbidities, kidney disease, atrial fibrillation, advanced functional class, inappropriate therapy risk, implantable device infections, and malfunctions are factors potentially reducing the expected benefit from defibrillating capabilities. In the future, prospective randomized controlled trials are warranted to directly compare the efficacy and safety of CRT-Ps and CRT-Ds.
Improving Outcomes in Cardiovascular Diseases: A Review on Vorapaxar
Authors: Chaudhary Rahul , Mohananey Akanksha , Sharma Sharan P. , Singh Sahib , Singh Amteshwar , Kondur Ashok
Published: March 2021

Antiplatelet agents are the standard of practice in the management of atherosclerosis and acute coronary syndrome. In contrast to the available antiplatelet agents, vorapaxar represents a novel mechanism of action. It is an antagonist of the platelet protease-activated receptor-1 and inhibits thrombin-induced and thrombin receptor agonist peptide-induced platelet aggregation. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50 (TRA 2°P-TIMI 50) trial led to the approval of vorapaxar by the Food and Drug Administration and European Medicines Agency for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (MI) or peripheral arterial disease. TRA 2°P-TIMI 50 trial showed that the use of vorapaxar (2.5 mg once/daily) in addition to standard dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor was effective in the secondary prevention of recurrent thrombotic events among patients with previous atherothrombosis, particularly in patients with prior MI; at the expense of an increase in major bleeding. Another recently published Vorapaxar Therapy in Patients With Prior Myocardial Infarction Treated With Newer Generation P2Y12 Receptor Inhibitors Prasugrel and Ticagrelor (VORA-PRATIC) study showed that among post-MI patients treated with potent P2Y12 inhibitors (prasugrel or ticagrelor), vorapaxar reduced platelet-driven global thrombogenicity, an effect that persisted, albeit attenuated, in the absence of aspirin. The current review summarizes an up-to-date literature on pharmacokinetics, pharmacodynamics, and clinical efficacy of vorapaxar and proposes future directions of research.
Real-World Experience With Antiplatelet Agents After Percutaneous Coronary Intervention in Patients With an Indication for an Oral Anticoagulant
Authors: Tanner Richard , Cronin Michael , Macken Lilly , Murphy Ross , Maree Andrew O. , Ullah Ihsan , Cosgrave John , O'Connor Stephen , Daly Caroline
Published: March 2021

Patients undergoing percutaneous coronary intervention (PCI) with a clinical indication for oral anticoagulation (OAC) in addition to antiplatelet therapy (APT) necessitate rigorous evaluation of bleeding and ischemic risk to guide therapy. The optimal OAC/APT drug combination and duration of treatment is not known. This study aimed to evaluate the incidence of patients undergoing PCI with an OAC indication and the rationale for post-PCI combined OAC/APT selection in clinical practice. Consecutive patients undergoing PCI with an indication for combined OAC/APT were included in a 12-month retrospective case series. Patient demographics, clinical characteristics, prescribed OAC/APT regimens, and rationale for drug selection were reviewed. PCI was performed in 1650 patients during the study period, with an indication for OAC/APT in 133 (8.1%). A combination of aspirin, P2Y12 inhibitor, and OAC was the most frequently prescribed regime on discharge (n = 103, 81%). Dual antiplatelet therapy (DAPT) in combination with OAC was continued for a mean duration of 6.4 ± 4.4 weeks (range 3–52 weeks) before one antiplatelet was discontinued. There was no significant difference between the mean CHA2DS2-VASc or HAS-BLED score of patients with atrial fibrillation discharged on OAC/DAPT compared with alternate combinations (DAPT alone or OAC/single APT), 3.6 ± 1.3 versus 3.8 ± 1, P = 0.37 and 2.04 ± 0.7 versus 2.05 ± 1.0, P = 0.98, respectively. This case series identifies high variability in OAC/APT treatment duration and limited application of risk scoring systems and high-risk PCI characteristics in the selection of OAC/APT regimens. A more systematic patient assessment is needed to help standardize OAC/APT prescribing for this important patient cohort.
Exosomes-Mediated LncRNA ZEB1-AS1 Facilitates Cell Injuries by miR-590-5p/ETS1 Axis Through the TGF-β/Smad Pathway in Oxidized Low-density Lipoprotein-induced Human Umbilical Vein Endothelial Cells
Authors: Chen Difang , Wang Kunwei , Zheng Yan , Wang Guangyu , Jiang Mei
Published: March 2021

Atherosclerosis is a chronic lipid-induced inflammation of the vessel wall. Oxidized low-density lipoprotein was confirmed to drive the onset of atherogenesis. Zinc finger e-box–binding homeobox 1 antisense 1 (ZEB1-AS1) is a long noncoding RNA that is involved in human diseases, including atherosclerosis. In this study, the role of exosomes-mediated ZEB1-AS1 and its underlying mechanisms in atherosclerosis were explored in oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs). Exosomes were extracted from HUVECs. Quantitative real-time polymerase chain reaction was conducted to measure the expression of ZEB1-AS1, microRNA-590-5p (miR-590-5p), or erythroblastosis virus E26 oncogene homolog 1 (ETS1) in cells or exosomes. Cell proliferation and apoptosis were assessed by MTT assay and flow cytometry analysis, respectively. Western blot was performed to detect apoptosis-related factors, ETS1, and TGF-β/Smad pathway protein levels. The secretion of inflammatory factors in supernatant was detected by ELISA assay. Oxidative stress damage indicators were used to assess cellular damage. Relationship between miR-590-5p and ZEB1-AS1 or ETS1 was analyzed. Our data indicated that ox-LDL–induced exosomes-mediated ZEB1-AS1 in HUVECs. Ox-LDL treatment resulted in limited proliferation, proapoptosis, inflammation, and oxidative stress damage, whereas knockdown of ZEB1-AS1 could reverse these effects. Mechanically, ZEB1-AS1 sponged miR-590-5p to regulate ETS1 expression. MiR-590-5p knockdown inverted effects above of si-ZEB1-AS1 on HUVECs under ox-LDL exposure. Moreover, ETS1 reversed miR-590-5p–induced effects and activated the TGF-β/Smad pathway in ox-LDL–treated HUVECs. Taken together, our findings demonstrated that exosomes-mediated ZEB1-AS1 enhanced cell injuries by miR-590-5p/ETS1 axis through the TGF-β/Smad pathway in ox-LDL–induced HUVECs, suggesting that inhibiting ZEB1-AS1 might be an effective way for atherosclerosis treatment.
Revisiting the Evidence for Dipyridamole in Reducing Restenosis: A Systematic Review and Meta-analysis
Authors: Simard Trevor , Motazedian Pouya , Dhaliwal Shan , Di Santo Pietro , Jung Richard G. , Ramirez Francisco Daniel , Labinaz Alisha , Short Spencer , Parlow Simon , Joseph Joanne , Rasheed Adil , Rockley Mark , Marbach Jeffrey , Domecq Marie-Cecile , Russo Juan J. , Chong Aun-Yeong , Beanlands Rob S. , Hibbert Benjamin
Published: March 2021

Atherosclerosis remains a leading cause of morbidity and mortality, with revascularization remaining a cornerstone of management. Conventional revascularization modalities remain challenged by target vessel reocclusion—an event driven by mechanical, thrombotic, and proliferative processes. Despite considerable advancements, restenosis remains the focus of ongoing research. Adjunctive agents, including dipyridamole, offer a multitude of effects that may improve vascular homeostasis. We sought to quantify the potential therapeutic impact of dipyridamole on vascular occlusion. We performed a literature search (EMBASE and MEDLINE) examining studies that encompassed 3 areas: (1) one of the designated medical therapies applied in (2) the setting of a vascular intervention with (3) an outcome including vascular occlusion rates and/or quantification of neointimal proliferation/restenosis. The primary outcome was vascular occlusion rates. The secondary outcome was the degree of restenosis by neointimal quantification. Both human and animal studies were included in this translational analysis. There were 6,839 articles screened, from which 73 studies were included, encompassing 16,146 vessels followed up for a mean of 327.3 days (range 7–3650 days). Preclinical studies demonstrate that dipyridamole results in reduced vascular occlusion rates {24.9% vs. 48.8%, risk ratio 0.53 [95% confidence interval (CI) 0.40–0.70], I2 = 39%, P < 0.00001}, owing to diminished neointimal proliferation [standardized mean differences −1.13 (95% CI −1.74 to −0.53), I2 = 91%, P = 0.0002]. Clinical studies similarly demonstrated reduced occlusion rates with dipyridamole therapy [23.5% vs. 31.0%, risk ratio 0.77 (95% CI 0.67–0.88), I2 = 84%, P < 0.0001]. Dipyridamole may improve post-intervention vascular patency and mitigate restenosis. Dedicated studies are warranted to delineate its role as an adjunctive agent after revascularization.
Nonsteroidal Mineralocorticoid Receptor Antagonists: Exploring Role in Cardiovascular Disease
Authors: Watson Kristin , Kukin Alina , Wasik Allie K. , Shulenberger Christine E.
Published: March 2021

Aldosterone, a mineralocorticoid hormone, plays a role in the pathophysiology of many cardiovascular disease states. Mineralocorticoid receptor antagonists (MRAs) have been shown to improve clinical outcomes in select patient populations. However, use of available steroidal receptor antagonists, eplerenone and spironolactone, is often limited by the risk or development of hyperkalemia. Nonsteroidal MRAs have been designed to overcome this limitation. The nonsteroidal MRAs have been studied in patients with heart failure with reduced ejection fraction, hypertension, and to lower the risk of cardiac and renal outcomes in those with type 2 diabetes and renal disease. In this review, the pharmacology of the MRAs is compared, the data evaluating the use of nonsteroidal MRAs are examined, and the place of this new generation of therapy is discussed. At this time, it seems that there could be a future role for nonsteroidal MRAs to reduce the risk of renal outcomes in high-risk individuals.
Efficacy and Safety of Ticagrelor in Diabetes Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials
Authors: Zhang Zeyi , Chen Ou
Published: March 2021

Dual antiplatelet treatment, consisting of aspirin and P2Y12 inhibitors, is essential for diabetes mellitus (DM) patients who have undergone percutaneous coronary intervention (PCI). This meta-analysis investigated whether ticagrelor, a novel P2Y12 inhibitor, was superior to clopidogrel and prasugrel in efficacy and safety for DM patients undergoing PCI. PubMed, the Cochrane Library and Google Scholar were searched for randomized controlled trials in which ticagrelor was administered. Eligible studies were independently scrutinized to extract data and assess the trials' quality. Statistical analysis was performed by calculating odds ratios (OR) and 95% confidence intervals (CI). A total of 8 studies consisting of 1056 patients were included. Results showed that ticagrelor reduced the major adverse cardiac events incidence compared with clopidogrel and prasugrel in the overall (OR = 0.40; 95% CI, 0.20–0.79; P = 0.008) and subgroup analyses compared with clopidogrel (OR = 0.39; 95% CI, 0.19–0.80; P = 0.01). No difference was observed in mortality rates (OR = 0.58; 95% CI, 0.23–1.45; P = 0.25), myocardial infarction (OR = 0.67; 95% CI, 0.28–1.60; P = 0.37), stroke (OR = 0.54; 95% CI, 0.10–3.01; P = 0.49), and total bleeding (OR = 1.70; 95% CI, 0.91–3.17; P = 0.10) between the ticagrelor and control groups. In DM patients undergoing PCI, ticagrelor significantly reduced major adverse cardiac events compared with clopidogrel and prasugrel in the overall and in the subgroup of clopidogrel. There was no difference regarding mortality, myocardial infarction, stroke, and bleeding. More randomized controlled trials are required to further validate these results.
Adverse Cerebral Cardiovascular Events Associated With Checkpoint Kinase 1 Inhibitors: A Systemic Review
Authors: Yang Tongtong , Gu Jie , Du Chong , Shan Tiankai , Wei Tianwen , Li Yafei , Wang Liansheng
Published: March 2021

Checkpoint kinase 1 (CHK1) plays a broad role in regulating the cell cycle process and is involved in the pathogenesis of various malignant tumors. Preclinical and animal studies have shown that CHK1 inhibitors can enhance the cytotoxic effects of radiotherapy and chemotherapy. Currently, CHK1 inhibitors are actively tested in clinical trials. Nonspecific adverse cerebral cardiovascular events were reported after CHK1 inhibitor use; these events need to be monitored and managed carefully during the clinical application of CHK1 inhibitors. To get a better understanding of these, noteworthy adverse cardiovascular events, we systemically searched the PubMed, Cochrane databases, and clinicaltrials.gov, for relevant clinical trials and case reports. A total of 19 studies were identified and included in this review. Among the reported cerebral cardiovascular events, the most common is incident abnormal blood pressure fluctuations (n = 35), followed by incident QTcF prolongation (n = 15), arrhythmia (n = 13, 3 atrial fibrillation and 10 bradycardia), thromboembolic events (n = 9, 6 pulmonary embolisms, 2 stroke, and 1 cerebrovascular event), cardiac troponin T elevation (n = 2), and ischemic chest pain (n = 2). Besides, the estimated incidence for overall cardiovascular events based on the available data is 0.292 (95% confidence interval: 0.096–0.488). CHK1 inhibitors administered in tumor patients on top of conventional therapies can not only enhance the antitumor effects, but also induce adverse cerebral cardiovascular events. It is, therefore, of importance to carefully monitor and manage the CHK1 inhibitor–induced adverse effects on the cerebral cardiovascular system while applying CHK1 inhibitors to tumor patients.
Quercetin Efficiently Alleviates TNF-α-Stimulated Injury by Signal Transducer and Activator of Transcription 1 and Mitogen-Activated Protein Kinase Pathway in H9c2 Cells: A Protective Role of Quercetin in Myocarditis
Authors: Yang Bin , Zheng Chun-Yan , Zhang Rui , Zhao Cong , Li Shan , An Yi
Published: March 2021

This study aimed to evaluate the protective effect of quercetin and its in-depth mechanism in TNF-α-stimulated cardiomyocytes. The differential expression of TNF-alpha (TNF-α) and signal transducer and activator of transcription 1 (STAT1) was analyzed based on the GEO database. H9c2 cells were stimulated with TNF-α to simulate myocarditis. Cell counting kit-8 assay and flow cytometry assay were performed to detect the cell viability and apoptosis. ELISA was used to measure the levels of proinflammatory cytokines (IL-6 and IL-17A) and anti-inflammatory cytokine (IL-10). STAT1 expression was downregulated by transfection with si-STAT1, and its expression was detected using quantitative real-time polymerase chain reaction and Western blot. Western blot was also performed to assess the expression of the mitogen-activated protein kinase (MAPK) pathway–related factors. In this article, TNF-α was highly expressed in patients with myocarditis, and TNF-α (20 μg/mL) declined the viability of H9c2 cells. Quercetin pretreatment partially alleviated the decrease of cell viability, the increase of apoptosis, and the release of inflammatory cytokines (IL-10, IL-6, and IL-17A) induced by TNF-α. In addition, TNF-α increased STAT1 expression, but quercetin prevented the TNF-α-increased STAT1 level. Remarkably, knockdown of STAT1 enhanced the protective effect of quercetin on TNF-α-injured H9c2 cells. Moreover, quercetin restrained the TNF-α-induced activation of the MAPK pathway. Also, the inhibitory effect of quercetin on the pathway was aggravated by STAT1 lacking. In summing, quercetin plays a protective role in TNF-α-stimulated H9c2 cell injury, which may be related to the regulation of STAT1 and MAPK pathway.
An Inconvenient Truth of Clinical Assessment and Indocyanine Green Angiography Precise Marking for Indeterminate Burn Excision
Authors: Wongkietkachorn Apinut , Surakunprapha Palakorn , Jenwitheesuk Kamonwan , Eua-angkanakul Kant , Winaikosol Kengkart , Punyavong Pattama , Wongkietkachorn Nuttapone , Wongkietkachorn Supawich , Salyapongse A. Neil
Published: March 2021

Background:

The clinical assessment of indeterminate burn wounds has relatively poor accuracy. Indocyanine green angiography (ICGA) has high accuracy and can be used to mark wounds precisely so as to guide burn excision. This study aimed to assess the differences between ICGA and clinical assessment marking and compare the marking result with the long-term wound outcome.

Methods:

This was a prospective, multicentered, triple-blinded, experimental study. Indeterminate burn wounds were clinically assessed, and the area to be excised was firstly marked by the attending surgeon. ICGA marking was then performed by a second surgeon. Measurement of the marked area was conducted by a third surgeon. Three surgeons were each blinded to the others' processes. The wounds were followed up to assess complete wound closures on day 21.

Results:

There were 20 burn sites included in the study. There was a significant difference in the marked areas between clinical assessment and ICGA (mean, 57.3 ± 44.1%; P = 0.001). The maximum difference found was as high as 160.9%. The correction rate of ICGA marking to complete wound closure on day 21 was 95.0%. Over 90% of the decreased areas of excision—which were assessed by ICGA to be superficial burns but evaluated by clinical assessment to be deep burns—were completely healed on day 21.

Conclusions:

ICGA contributes to a significant difference versus clinical assessment in the marking for excision of indeterminate burns and strongly associates with long-term wound outcomes. The burn wounds can be assessed precisely to reduce unnecessary excision and prevent inadequate excision.
Trends in Physical Activity Among US Adults With Heart Failure, 2007-2016
Authors: Ye Fan , Yale Steven , Zheng Yi , Hu Hui , Zhou Li , Fanning Jason , Yeboah Joseph , Brubaker Peter , Bertoni Alain G.
Published: March 2021

Purpose:

Lack of physical activity (PA) is an important risk for heart failure (HF). The objective of this study was to examine PA trends in HF and non-HF participants from a nationally representative sample of US adults from 2007 to 2016.

Methods:

Work-related/recreational activities (min/wk) were calculated on the basis of the reported frequency, intensity, and duration, respectively. Multivariable analyses were performed using National Health and Nutrition Examination Survey data.

Results:

Among 28 824 participants, younger (aged 18-64 yr) HF participants reported less PA time than non-HF groups, especially vigorous PA. Differences were found to be smaller in older (≥ 65 yr) participants. Overall, the percentage of younger participants who met PA guidelines was significantly lower in the HF individuals in work-related PA and total PA from 2007 to 2016 than in the non-HF participants (OR = 0.55: 95% CI, 0.39-0.59 for total PA, 0.45, 0.28-0.75 for vigorous work-related PA, and 0.68, 0.47-0.97 for moderate work-related PA, respectively). In older participants, only when considering total PA, the prevalence of meeting PA guidelines was significantly different between HF and non-HF groups (0.78, 0.62-0.98).

Conclusions:

Self-reported PA, especially vigorous activities, is much lower in older HF participants. However, the disparity in meeting PA guidelines between those with HF and without HF is remarkable in younger individuals. Future research should focus on better understanding the psychological and physical barriers to engaging in PA among HF patients.
Area Deprivation Index and Cardiovascular Events
Authors: Guhl Emily N. , Zhu Jianhui , Johnson Amber , Essien Utibe , Thoma Floyd , Mulukutla Suresh R. , Magnani Jared W.
Published: March 2021

Introduction:

Neighborhood socioeconomic status is associated with health outcomes. Cardiac rehabilitation (CR) provides a cost-effective, multidisciplinary approach to improve outcomes in cardiovascular disease. We aimed to evaluate the association of the Area Deprivation Index (ADI), a marker of neighborhood social composition, with risk of recurrent cardiovascular outcomes and assessed the modifying effect of CR.

Methods:

We identified patients with a primary diagnosis of (1) myocardial infarction or (2) incident heart failure (HF) admitted to a large-sized regional health center during 2010-2018. We derived the ADI from home addresses and categorized it into quartiles (higher quartiles indicating increased deprivation). We obtained number of CR visits and covariates from the health record. We compared rehospitalization (cardiovascular, acute coronary syndrome [ACS], and HF) and mortality rates across ADI quartiles.

Results:

We included 6957 patients (age 69.2 ± 13.4 yr, 38% women, 89% White race). After covariate adjustment, the ADI was significantly associated with higher incidence rates (IRs)/100 person-yr of cardiovascular rehospitalization (quartile 1, IR 34.6 [95% CI, 31.2-38.2]; quartile 4, 41.5 [95% CI, 39.1-44.1], P < .001). In addition, the ADI was significantly associated with higher rates of rehospitalization for HF (P < .001), ACS (P < .012), and all-cause mortality (P < .04). These differences in rehospitalization and mortality rates by the ADI were no longer significant in those who attended CR.

Conclusions:

We found the increased ADI was adversely associated with rehospitalizations and mortality. However, in individuals with CR, outcomes were significantly improved compared with those with no CR. Our findings suggest that CR participation has the potential to improve outcomes in disadvantaged neighborhoods.
The Effectiveness of Cardiopulmonary Rehabilitation Programs on Psychosocial Factors in Patients With Pulmonary and Cardiac Disease
Authors: Alqahtani Mohammed M. , Alanazi Abdulla M. M. , Yohannes Abebaw Mengistu , Smith Caitlin E. , Goodfellow Lynda T.
Published: March 2021

Purpose:

Those with chronic cardiac and pulmonary diseases are predisposed to several psychosocial disorders. Tailored rehabilitation programs have been shown to improve physiological and psychosocial well-being. The purpose of this study was, first, to assess the psychosocial improvements among patients with cardiac and pulmonary diseases who have finished cardiac rehabilitation (CR) and pulmonary rehabilitation (PR) programs; second, to assess the differences in psychosocial factors among those patients based on smoking status at the beginning and end of these programs.

Methods:

The CR and PR programs in hospital settings were retrospectively analyzed from 2013-2018. Before and after, all patients completed the sociodemographic characteristics along with the Psychosocial Risk Factor Survey that measures total distress, depression, anxiety, hostility, and social isolation.

Results:

There were 355 patients with cardiac and 244 patients with pulmonary disease who completed 6- to 12-wk CR or PR programs. There were significant improvements in all psychosocial symptoms among cardiac patients. Patients with pulmonary disease exhibited significant improvements in all psychosocial factors except for social isolation. Moreover, current smokers in the CR group reported elevated symptoms of several psychosocial scores.

Conclusion:

These findings provide critical information about the effects of tailored rehabilitation programs among patients with chronic cardiac and pulmonary diseases on psychosocial levels. By using the Psychosocial Risk Factor Survey, we have found that total distress, depression, anxiety, and hostility were reduced among patients who completed the CR or PR programs. Current smokers exhibited the elevated mean scores on psychosocial symptoms in the cardiac group that may be a target for smoking cessation program. The advantages of tailored rehabilitation programs are significant, which may be of benefit for physical, social, behavioral, and psychological well-being.
Short-Term Outcomes of Pediatric Keratoprosthesis With the Near-Complete Conjunctival Flap
Authors: Bawany Mohammad H. , Kudla Callais , Khan Faraaz A. , Chung Mina M. , Aquavella James V.
Published: March 2021

Purpose:

The Boston keratoprosthesis (KPro) has been used for certain indications in pediatric patients with congenital corneal opacities. Here, we describe the use of a near-complete conjunctival flap at the time of Boston type 1 KPro surgery in pediatric patients, with the goal of improving pediatric KPro outcomes.

Methods:

We performed a retrospective chart review of 21 eyes from 16 patients who received their first KPro before the age of 18 years at a tertiary care center in Rochester, NY. Surgeries were performed between 2011 and 2017 (3 years before and after the incorporation of a conjunctival flap, which began in 2014 as part of the pediatric KPro procedure). Patients who had a minimum 1-year postoperative follow-up, or had corneal melts within 1 year of KPro implantation, were included in our study. The main outcome measure in this study was a comparison of the number of complications that required surgical intervention, including retroprosthetic membrane, corneal melt, retinal detachment, and endophthalmitis, in eyes that received KPro implantation without a conjunctival flap compared with eyes that received KPro implantation with a conjunctival flap. Change in the visual acuity up to 1 year postoperatively was also measured.

Results:

Ten eyes received KPro with no conjunctival flap, and 11 eyes received KPro with a near-complete conjunctival flap. After 1-year postoperative follow-up, eyes receiving a KPro with a conjunctival flap had fewer KPro-related complications requiring surgical intervention (5 vs. 16, P = 0.0002). Corneal melt was seen in 2 of 11 (18%) eyes in the conjunctival flap group and 5 of 10 (50%) eyes in the nonflap group (P = 0.12). No eyes developed endophthalmitis in the flap group, whereas 1 of 10 (10%) eyes developed endophthalmitis in the nonflap group. Visual acuity at 1-year follow-up improved in 9 of 11 (82%) eyes in the flap group compared with 5 of 10 (50%) eyes in the nonflap group (P = 0.3).

Conclusions:

Implementation of a conjunctival flap in pediatric KPro may help decrease the short-term postoperative complications requiring surgical procedures and may lead to improved visual acuity after 1 year. Further investigation, including longer-term follow-up, is needed to better understand how the described technique affects surgical outcomes in children.
Comparison of Pterygium Recurrence Rates Between Attending Physicians and Supervised Trainee Residents
Authors: Thompson John P. , Harbin Zach , Das Hrishikesh , Deschner Lauren A. , Seale Stephanie A. , Kheirkhah Ahmad
Published: March 2021

Purpose:

To compare the recurrence rates after pterygium surgery performed by supervised trainee residents and attending physicians.

Methods:

This retrospective study included pterygium surgeries performed by trainee residents and attending physicians in an academic institution in South Texas in the years 2008 to 2019. All residents performed surgeries under direct supervision of an attending physician. Only primary pterygium cases with a minimum postoperative follow-up of 6 months were included. Patients' demographics, primary surgeon, use of conjunctival autograft (CAU) or amniotic membrane graft (AMG), recurrence of pterygium, follow-up length, and complications were recorded.

Results:

This study included 240 eyes of 229 patients with a mean age of 55.6 ± 12.3 years (range, 28–91 years). Of these eyes, 100 surgeries were performed by attending physicians (including 87 with CAU and 13 with AMG) and 140 surgeries by trainee residents (including 119 with CAU and 21 with AMG). There were no significant differences between the 2 groups of patients regarding age, sex, and surgical technique (CAU vs. AMG). Patients were followed up for an average of 19.8 ± 15.2 months. No statistically significant differences were found in comparing the rate of pterygium recurrence between attending physicians and residents when using CAU (6.8% vs. 10.0%, respectively; P = 0.42) and AMG (69.2% vs. 47.6%, respectively; P = 0.22). Moreover, there were no significant differences in other postoperative complications between the groups.

Conclusions:

Pterygium recurrence rates were similar between attending physicians and supervised trainee residents. Thus, acceptable outcomes can be expected when pterygium surgery is performed by a supervised ophthalmology resident.
The Impact of Gender on the Effectiveness of an Auricular Acupressure Intervention Administered to Community-Dwelling Poor Sleepers: A Cluster Randomized Controlled Trial
Authors: HUNG Hsuan-Man , CHIANG Hsiao-Ching , WANG Hui-Ling
Published: March 2021

Background

Women report a higher incidence of sleep problems than men. Few studies addressing the effect of gender on the efficacy of administering auricular acupressure (AA) at shenmen points (heart meridian 7 [HT7]) on sleep quality have been published.

Purpose

The primary aim of this study was to investigate the effects of a 4-week AA intervention applied at the HT7 points on sleep quality, perceived physical health, and perceived mental health in community-dwelling individuals with poor self-reported sleep quality. Additional analyses were used to evaluate the gender-specific effects of this intervention.

Methods

A cluster randomized controlled trial with repeated-measures design was used. One hundred seventy-nine eligible participants were randomly assigned to either the AA group (n = 88; 47 women, 41 men) or the sleep hygiene instruction (SHI) group (n = 91; 52 women, 39 men). The AA group self-administered acupressure at HT7 on both ears for a 4-week period, whereas the SHI group received an SHI information sheet. Outcome measures included the Pittsburgh Sleep Quality Index (PSQI) and the Short-Form Health Survey-12 Version 2, with data collected at baseline and at 2, 4, and 8 weeks posttest.

Results

Linear mixed-model analysis revealed that the participants in the AA group experienced significantly greater reductions in mean PSQI global score and the three indices of sleep latency, subjective sleep quality, and daytime dysfunction than the SHI group at 2 and 4 weeks posttest. The improvements in subjective sleep quality and daytime dysfunction remained at 4 weeks posttest in the AA group, but not in the SHI group. The PSQI global score decreased significantly more in men than women in the AA group between baseline and 4 weeks posttest.

Conclusions/Implications for Practice:

Four weeks of self-administered acupressure at HT7 on both ears is an effective intervention for community-dwelling poor sleepers who are over 45 years old. Moreover, the improvements in subjective sleep quality and daytime dysfunction persist for up to 4 weeks after the end of the intervention. This self-administered acupressure intervention is more effective in men than in women in terms of improving sleep quality. Gender bias is known to influence research results and may lead to inappropriate generalizations. Thus, future studies that are performed to build basic scientific evidence should include considerations of the effects of gender in the study design.
Nuclear EGFR Expression Is Associated With Poor Survival in Laryngeal Carcinoma
Authors: Marijić Blažen , Braut Tamara , Babarović Emina , Krstulja Mira , Maržić Diana , Avirović Manuela , Kujundžić Milodar , Hadžisejdić Ita
Published: March 2021

The membrane EGFR (mEGFR) protein overexpression in the head and neck squamous cell carcinoma (SCC) is considered to cause increased EGFR activity which adds to tumorigenicity and therapy resistance. The mEGFR upon stimulation can translocate to the nucleus nuclear EGFR (nEGFR) where it has been associated with poor prognosis and worse survival in many cancers. The relevance of differentially located EGFR proteins in laryngeal lesions has not been studied enough and remains unclear. Aim of our study was to examine nEGFR and mEGFR protein expression as well as EGFR gene status and cell cycle proliferation markers in the laryngeal polyps, dysplasia, and SCC using immunohistochemistry and in situ hybridization. There was significantly higher frequency of strong nEGFR between SCC, dysplasia, and polyps (P<0.0001), and strong mEGFR in the SCC and laryngeal dysplasia comparing to polyps (P<0.0001). Gene amplification was confirmed only in relatively small number of SCC but not in non-neoplastic lesions. In dysplasia the statistically significant positive correlations between nEGFR, and Ki-67 (P=0.029), p53 (P=0.001), and cyclin D1 (P=0.031) were found. nEGFR and mEGFR expression showed statistically significant inverse correlation in the SCC (P=0.004) as well as nEGFR and cyclin D1 (P=0.032). Univariate statistical analysis showed statistically significant correlation between strong nEGFR protein expression and worse overall survival in laryngeal SCC, alone or in coexpression with strong cyclin D1 and high Ki-67 (P=0.025, P=0.046, P=0.043, respectively). Our data show that nEGFR cellular localization might influence biology of the laryngeal carcinogenesis and is indicator of poor survival.
SP142 PD-L1 Scoring Shows High Interobserver and Intraobserver Agreement in Triple-negative Breast Carcinoma But Overall Low Percentage Agreement With Other PD-L1 Clones SP263 and 22C3
Authors: Pang Jia-Min B. , Castles Belinda , Byrne David J. , Button Peter , Hendry Shona , Lakhani Sunil R. , Sivasubramaniam Vanathi , Cooper Wendy A. , Armes Jane , Millar Ewan K.A. , Raymond Wendy , Roberts-Thomson Samuel , Kumar Beena , Burr Marian , Selinger Christina , Harvey Kate , Chan Charles , Beith Jane , Clouston David , O’Toole Sandra A. , Fox Stephen B.
Published: March 2021

SP142 programmed cell death ligand 1 (PD-L1) status predicts response to atezolizumab in triple-negative breast carcinoma (TNBC). Prevalence of VENTANA PD-L1 (SP142) Assay positivity, concordance with the VENTANA PD-L1 (SP263) Assay and Dako PD-L1 IHC 22C3 pharmDx assay, and association with clinicopathologic features were assessed in 447 TNBCs. SP142 PD-L1 intraobserver and interobserver agreement was investigated in a subset of 60 TNBCs, with scores enriched around the 1% cutoff. The effect of a 1-hour training video on pretraining and posttraining scores was ascertained. At a 1% cutoff, 34.2% of tumors were SP142 PD-L1 positive. SP142 PD-L1 positivity was significantly associated with tumor-infiltrating lymphocytes (P <0.01), and node negativity (P=0.02), but not with tumor grade (P=0.35), tumor size (P=0.58), or BRCA mutation (P=0.53). Overall percentage agreement (OPA) for intraobserver and interobserver agreement was 95.0% and 93.7%, respectively, among 5 pathologists trained in TNBC SP142 PD-L1 scoring. In 5 TNBC SP142 PD-L1-naive pathologists, significantly higher OPA to the reference score was achieved after video training (posttraining OPA 85.7%, pretraining OPA 81.5%, P<0.05). PD-L1 status at a 1% cutoff was assessed by SP142 and SP263 in 420 cases, and by SP142 and 22C3 in 423 cases, with OPA of 88.1% and 85.8%, respectively. The VENTANA PD-L1 (SP142) Assay is reproducible for classifying TNBC PD-L1 status by trained observers; however, it is not analytically equivalent to the VENTANA PD-L1 (SP263) Assay and Dako PD-L1 IHC 22C3 pharmDx assay.
Feasibility and Performance of Elastin Trichrome as a Primary Stain in Colorectal Cancer Resection Specimens
Authors: Shivji Sameer , Kak Ipshita , Reid Stephanie L. , Muir Jennifer , Hafezi-Bakhtiari Sara , Li-Chang Hector , Deliallisi Ardit , Newell Ken J. , Grin Andrea , Conner James , Kirsch Richard
Published: March 2021

Venous invasion (VI) is a powerful prognostic factor in colorectal cancer (CRC) that is widely underreported. The ability of elastin stains to improve VI detection is now recognized in several international CRC pathology protocols. However, concerns related to the cost and time required to perform and evaluate these stains in addition to routine hematoxylin and eosin (H&E) stains remains a barrier to their wider use. We therefore sought to determine whether an elastin trichrome (ET) stain could be used as a “stand-alone” stain in CRC resections, by comparing the sensitivity, accuracy, and reproducibility of detection of CAP-mandated prognostic factors using ET and H&E stains. Representative H&E- and ET-stained slides from 50 CRC resections, including a representative mix of stages and prognostic factors, were used to generate 2 study sets. Each case was represented by H&E slides in 1 study set and by corresponding ET slides from the same blocks in the other study set. Ten observers (3 academic gastrointestinal [GI] pathologists, 4 community pathologists, 3 fellows) evaluated each study set for CAP-mandated prognostic factors. ET outperformed H&E in the assessment of VI with respect to detection rates (50% vs. 28.6%; P<0.0001), accuracy (82% vs. 59%, P<0.0001), and reproducibility (k=0.554 vs. 0.394). No significant differences between ET and H&E were observed for other features evaluated. In a poststudy survey, most observers considered the ease and speed of assessment at least equivalent for ET and H&E for most prognostic factors, and felt that ET would be feasible as a stand-alone stain in practice. If validated by others, our findings support the use of ET, rather than H&E, as the primary stain for the evaluation of CRC resections.
Imaging of the Pericoronary Adipose Tissue (PCAT) Using Cardiac Computed Tomography
Authors: Goeller Markus , Achenbach Stephan , Duncker Hendrik , Dey Damini , Marwan Mohamed
Published: March 2021

Modern coronary computed tomography angiography (CTA) is the gold standard to visualize the epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT). The EAT is a metabolic active fat depot enclosed by the visceral pericardium and surrounds the coronary arteries. In disease states with increased EAT volume and dysfunctional adipocytes, EAT secretes an increased amount of adipocytokines and the resulting imbalance of proinflammatory and anti-inflammatory mediators potentially causes atherogenic effects on the coronary vessel wall in a paracrine way (“outside-to-inside” signaling). These EAT-induced atherogenic effects are reported to increase the risk for the development of coronary artery disease, myocardial ischemia, high-risk plaque features, and future major adverse cardiac events. Coronary inflammation plays a key role in the development and progression of coronary artery disease; however, its noninvasive detection remains challenging. In future, this clinical dilemma might be changed by the CTA-derived analysis of the PCAT. On the basis of the concept of an “inside-to-outside” signaling between the inflamed coronary vessel wall and the surrounding PCAT recent evidence demonstrates that PCAT computed tomography attenuation especially around the right coronary artery derived from routine CTA is a promising imaging biomarker and “sensor” to noninvasively detect coronary inflammation. This review summarizes the biological and technical principles of CTA-derived PCAT analysis and highlights its clinical implications to improve modern cardiovascular prevention strategies.
Introducing a Radiography-based Score in Children With Acute Respiratory Failure
Authors: Raissaki Maria , Ilia Stavroula , Katsoula Vasiliki , Kotziamanis Alexandros , Theotokatou Despoina , Briassoulis George
Published: March 2021

Purpose:

Respiratory failure (RF) is one of the most common reasons for hospitalization in pediatric intensive care units (PICU). We propose a radiography-based severity score for the assessment of children with RF and investigate the possible associations with severity indices and outcome.

Materials and Methods:

Children with acute RF admitted in PICU were enrolled. Disease severity scores [Pediatric Risk of Mortality (PRISM) and Pediatric Logistic Organ Dysfunction (PELOD)], the ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO2/FiO2) ratios, duration of ventilator support (DVS), length of PICU and hospital stay (LOS), and outcome were recorded. A 5-point radiography score that considered potential radiographic findings was derived through stepwise multivariable logistic regression analysis, and validated. Radiographs upon PICU admission and on the worst RF day (maximum respiratory support and worst oxygenation/ventilation parameters) were blindly reviewed and independently scored by 2 radiologists and 2 clinicians, following training.

Results:

We enrolled 104 children [median age 2.7 (interquartile range, 0.5 to 9.6) y, 65.4% boys]. Overall, 163 radiographs (PICU admission: 86, worst RF day: 77) were assessed. Radiography scores correlated positively with predicted mortality (PELOD, PRISM), DVS, LOS (all P<0.001) and inversely with PaO2/FiO2 (P<0.001). Scores differed among diagnostic categories (P<0.05); patients with acute respiratory distress syndrome, air-leaks, drowning, and pneumonia scored the highest (P<0.005). Radiography scoring trends indicating deterioration were associated with prolonged DVS, PICU, and hospital LOS (P<0.001). Agreement between all raters was good (κ=0.7, P<0.001).

Conclusions:

This novel radiography score for children with RF, associated with clinical severity scores, mortality risk, duration of ventilatory support, and hospitalization, follows a simple structured approach and can be readily utilized by radiologists and pediatricians as a bedside tool for stratification of disease severity and prognosis.
Thoracic Multidetector Computed Tomography Findings of Dedicator of Cytokinesis 8 Deficiency in Children
Authors: Lee Edward Y. , Vargas Sara O. , Gaffin Jonathan M. , Chou Janet , Park Halley J. , Winant Abbey J.
Published: March 2021

Purpose:

To investigate the characteristic thoracic multidetector computed tomography (MDCT) findings of dedicator of cytokinesis 8 (DOCK8) deficiency, a rare autosomal recessive form of hyperimmunoglobulin E syndrome, in children.

Materials and Methods:

All pediatric patients (age 18 y and below) with a known diagnosis of DOCK8 deficiency based on genetic testing who underwent thoracic MDCT studies from November 2004 to November 2020 were included. Two pediatric radiologists independently evaluated MDCT studies for the presence of thoracic abnormalities in the lung [ground-glass opacity (GGO), consolidation, pulmonary nodule, mass, cyst, and bronchiectasis], pleura (pleural effusion and pneumothorax), and mediastinum (lymphadenopathy). When a lung abnormality was present, laterality, distribution (upper, middle, and lower lung zone), and extent were also evaluated. When a pleural abnormality was identified, laterality and size of the abnormality were also assessed. When mediastinal lymphadenopathy was present, its location and size were also evaluated. Interobserver agreement between two independent reviewers was evaluated with κ statistics.

Results:

In all, 17 thoracic MDCT studies from 17 individual pediatric patients [5 males (29%) and 12 females (71%); mean age: 7.4 y; SD: 3.7; range: 1 to 13 y] comprised the final study population. Among 17 thoracic MDCT studies, 11 studies (65%) were performed with intravenous contrast (IV) and the remaining 6 MDCT studies (35%) were obtained without IV contrast. Bilateral bronchiectasis (11/17; 65%) with a middle lung zone predominance (8/11; 73%) was the most frequently detected lung abnormality, followed by GGO in 9/17 patients (53%). Among 11 contrast-enhanced MDCT studies, the majority (9 patients, 82%) had mediastinal lymphadenopathy. There was excellent interobserver κ agreement between 2 independent reviewers for detecting abnormalities on thoracic MDCT studies (κ>0.90).

Conclusion:

Children with DOCK8 deficiency have characteristic thoracic MDCT findings, including bilateral bronchiectasis with a middle lung zone predominance, GGO, and mediastinal lymphadenopathy. When these characteristic thoracic MDCT findings are detected, although rare, DOCK8 deficiency should be considered as a possible underlying diagnosis in the pediatric population.
Philip George Burke. 18 October 1932—4 June 2019
Authors: Hibbert Alan
Published: March 2021

The development of theoretical and computational atomic and molecular physics in the second half of the twentieth century owes a great deal to Phil Burke. His knowledge and insight, his enthusiasm and encouragement, his vision and determination were essential characteristics for the success of his work and that of many others. He developed and used the R-matrix method in the study of the interaction between, on the one hand, atoms and molecules and their ions and, on the other, light or electrons. He published many original research papers and was author or editor of a number of books. Especially significant and far-reaching was his setting up of the journal
Computer Physics Communications
to enable an international field of scientists, initially to share computer codes, but subsequently also to discuss and develop methods in computational physics. While based at the Daresbury Laboratory, he established a number of Collaborative Computational Projects, thus providing a forum for scientists working in specific scientific disciplines to meet periodically to discuss current issues and in particular how the ever advancing cutting-edge of high-end computing could begin to address previously intractable problems. A consequence was his clarity of thinking about which new computer architectures were needed to make significant advances in each field of study, expertly guiding the UK's provision of high-end computers to academia for over 20 years. He was a clear and methodical teacher, at both graduate and undergraduate level, and was generous with the time he gave to his students. In short, he demonstrated a balanced level of excellence in all aspects of his career. He was a consummate academic and a fine role model for his colleagues.