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Aim: We aimed to evaluate (immunohistochemically) the YAP expression in breast cancer patients undergoing neoadjuvant chemotherapy and to clarify the relationship between the molecular characteristics, treatment response and survival data and the YAP expression, and hence, to clarify the prognostic significance. Methods: One hundred and four patients who were admitted to Erciyes University Faculty of Medicine after the approval of the Ethics Committee and were diagnosed with Breast Cancer between 2015-2020 and underwent NeoAdjuvant Chemotherapy were included in the study. The diagnoses of these patients were determined by any of the methods of Breast USG, Mammography, Breast MRI and, if necessary, PET/CT, and among pathological samples, Estrogen Receptor (ER), Progesterone Receptor (PR), Human Epidermal Growth Receptor-2 (HER2) and Ki-67 Expression are routinely stained immunohistochemically. In this study, existing immunohistochemical markers were reviewed and also, the relationship of YAP with these biological markers was evaluated by using immunohistochemistry and its effect on prognosis has been investigated. Results: The average age of the patients was 52.37. While YAP was positive in 78 patients (75%), it was negative in 26 patients (25%). In the evaluation after neoadjuvant therapy, pathological complete response (Miller Payne Grade 5 response) in 28 patients (26.9%), relapse in 6 patients (5.8%), and exitus in 6 patients (5.8%) were detected. In the pathological evaluation, invasive Ductal Carcinoma was the most common one observed in 88 patients (84.6%). As a result of the statistical evaluation, no significant result was obtained between the parameters and YAP negative / positive. Conclusion: As a result of staining with additional YAP in patients who were diagnosed with breast cancer and routinely stained with ER, PR, Cerb B2 and Ki-67 in pathology samples, we could not reach a result that would contribute positively to survival. Longer studies to be conducted prospectively will be meaningful.

Jennette Higgs

and 4 more

Background Essential training for emergency adrenaline auto-injector administration alone provides inadequate safeguard in school environments. Recent UK deaths have reinforced the urgency for embedding whole school (WS) allergy awareness to minimise risk. We document development of a practical, flexible WS Food Allergy Awareness Toolkit for UK secondary schools. Methods We used a multidisciplinary participatory action research methodology, involving successive modification and retesting of a pragmatic toolkit in 3 case study schools. A School Allergy Action Group drives WS risk assessment, helping schools gradually implement best practice policy in line with their particular needs. Additional schools self-piloted the resulting toolkit with only remote monitoring. School surveys, based on EAACI guidelines were developed to identify priorities and assess change. Results Effectiveness of the resulting process toolkit, now available online, was independently demonstrated via pre/post intervention questionnaires from 24/10 pupils with food allergy (FA) and 97/6 pupils without FA, respectively. Pearson correlational analysis showed strong negative relationships between Food Allergy Quality of Life Questionnaire (FAQLQ) at T0 and School Support (SS) at T0 (r=-0.8, p<0.01), and between SS and Self-Efficacy (SE) (r=0.73, p<0.05). Mean FAQLQ scores improved between T0 (3.3) and T1 (2.5). SE improved for those with FA (mean difference =1.0). In those without FA, SE (mean difference =0.9) and Attitudes and Knowledge (mean difference =0.7) also improved. Conclusions Full stakeholder involvement in toolkit development encourages usage and therefore improves WS community awareness; reduces risk of reactions; fosters a more accepting societal attitude; and empowers pupils with/without allergies to self-manage effectively.

Bingwu Huang

and 5 more

Background and purpose: TwHF has been used in traditional Chinese medicines for treating CVD. However, the underlying pharmacological mechanisms of the effects of TwHF against CVD remain to be elucidated. The aim of the present study is to reveal the pharmacological mechanisms of TwHF acting on CVD based on a pharmacology approach. Experimental approach: The active compounds were screened by TCMSP according to ADME. The potential targets of TwHF were predicted by SwissTargetPrediction database. The CVD-related therapeutic targets were obtained by the DrugBank, the OMIM database and the GeneCards database. PPI network was constructed by STRING database. GO and KEGG pathway enrichment analyses were performed by R package. The network of drug‐targets-diseases-pathways was constructed by Cytoscape software. Key results: A total of 51 effective ingredients of TwHF and the 178 common targets of TwHF and CVD-related were collected. AKT1, APP, MAPK, PIK3CA and TP53 was identified the core targets involved in the action of TwHF on CVD. Top ten GO and KEGG pathways were identified with a P value ≤ 0.01. Finally, we constructed the network of TwHF-targets-CVD-GO-KEGG. Conclusion and implications: Our results demonstrated that the main active compound of TwHF exerts cardiovascular protective effects and the core targets and pathways associated with the effects of TwHF on CVD. By the construction of the network of TwHF-targets-CVD-GO-KEGG, network pharmacology uncovered the pharmacological mechanisms of the action of TwHF on CVD and indicated a novel perspective to identify the intricate interactions among TwHF, candidate targets and related pathways.

Xide Hu

and 17 more

Background and Purpose: Sex hormones affect heart rhythm by regulating ion channels, but the effect of estrogen on cardiac voltage-gated sodium channel in stress-induced pathological conditions is currently not well defined. In this study, we explored the impact of various concentrations of estrogen and the role of its rapid receptor G protein-coupled estrogen receptor (GPER) on sodium channel function in a simulated cardiac stress model of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Experimental Approach: Isoproterenol treated hiPSC-CMs were pre-incubated with various concentrations of β-Estradiol. Their sodium channel electrophysiological function and action potential were dissected by patch clamp and the content of sodium channel was observed by immunohistochemical method combined with laser scanning confocal microscopy. The GPER-specific effect was determined with agonists G1, antagonists G15 and small interfering RNA and sodium channel electrophysiology was selectively detected. Key Results: Isoproterenol-induced stress increased peak sodium current and late sodium current, and shortened action potential duration but the effects of stress were eliminated by β-Estradiol. Pearson Correlation analysis demonstrated no association between estrogenic effects on sodium currents versus content of sodium channel. Activation of GPER produced similar effects as β-Estradiol, while inhibition of GPER cancelled the effects induced by β-Estradiol. Conclusion and Implications: Estrogen through its rapid signal receptor GPER ameliorated the detrimental effects of β-adrenergic overstimulation like in cardiac stress on sodium channel dysfunction in hiPSC-CMs. These results are of great clinical significance as we need to understand the role of sex hormones in cardiovascular disease.

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Gary Ghahremani

and 2 more

Summary Background: Torus is a protuberant and lobulated exostosis that develops on the lingual aspect of the jaws or hard palate in 10-30% of adults. They can interfere with mastication, speech, oral hygiene, and denture placement. Their enlargement with advancing age may also lead to superficial ulceration, inflammation, osteonecrosis and various other complications. Methods: A retrospective analysis of the authors’ experience with 17 adults who had large symptomatic tori was performed. The patients were examined by intraoral imaging and radiographic or computed tomography of their maxillofacial bones. Their dental and medical records were reviewed along with the pertinent literature concerning the prevalence and reported complications of this entity. Results: This series included 6 men and 11 women, ranging in age from 36 to 85 years (Mean age: 56.5 years).There were 6 patients with torus mandibularis, 8 with torus palatinus, and 3 with torus maxillaris. Four of our 17 patients required surgical excision of their tori because of large size, recurrent superficial erosions and associated symptoms. Conclusion: The majority of tori are asymptomatic and incidental finding, but the more prominent tori are prone to mucosal inflammation and ulceration that may require surgical removal of the lesion. Large tori can also interfere with mastication, speech, dental hygiene, placement and function of prosthetic dentures, and may cause snoring, sleep apnea or other complications. Therefore, the practicing physicians should be familiar with the appearance, radiological features, clinical implications and management of tori.

Wahaj Munir

and 3 more

Background: Acute type A aortic dissection (ATAAD), is a surgical emergency often requiring intervention on the aortic root. There is much controversy regarding root management; aggressively pursuing a root replacement, versus more conservative approaches to preserve native structures. Methods: Electronic database search we performed through PubMed, Embase, SCOPUS, google scholar and Cochrane identifying studies that reported on outcomes of surgical repair of ATAAD through either root preservation or replacement. The identified articles focused on short- and long-term mortalities, and rates of re-operation on the aortic root. Results: There remains controversy on replacing or preserving aortic root in ATAAD. Current evidence supports practice of both trends following an extensive decision-making framework, with conflicting series suggesting favourable results with both procedures as the approach that best defines higher survival rates and lower perioperative complications. Yet, the decision to perform either approach remains surgeon decision and bound to the extent of the dissection and tear entries in strong correlation with status of the aortic valve and involvement of coronaries in the dissection. Conclusions: There exists much controversy regarding fate of the aortic root in ATAAD. There are conflicting studies for impact of root replacement on mortality, whilst some study’s report no significant results at all. There is strong evidence regarding risk of re-operation being greater when root is not replaced. Majority of these studies are limited by the single centred, retrospective nature of these small sample sized cohorts, further hindered by potential of treatment bias.

Matthew Sussman

and 9 more

The recognition of fibrinolysis phenotypes in trauma patients has led to a reevaluation of antifibrinolytic therapy (AF). Many cardiac patients also receive AF, however the distribution of fibrinolytic phenotypes in that population is unknown. The purpose of this study was to fill that gap. Methods: Data were retrospectively reviewed from 78 cardiac surgery patients. Phenotypes were defined as hypofibrinolytic (LY30 <0.8%), physiologic (LY30 0.8-3.0%) and hyperfibrinolytic (LY30 >3%). Continuous variables were expressed as M ± SD or median (interquartile range). Results: The study population was 65±10 yrs old, 74% male, average body mass index of 29±5 kg/m2. Fibrinolytic phenotypes were distributed as physiologic=45%, hypo=32% and hyper = 23%. There was no obvious effect of age, gender, race, or ethnicity on the distribution of fibrinolysis phenotypes; 47% received AF. The time with chest tube during post-operative recovery was longer in those who received AF (4[3,5] days) vs no AF (3[2,4] days), P=0.037). All cause morbidity occurred in 51% of patients who received AF vs 25% with no AF (p=0.017). However, with AF vs no AF, apparent differences in median chest tube output (1379 vs 820ml, p=0.075), hospital LOS (13 vs 10 days, P=0.873), estimated blood loss (1100 vs 775 ml, P=0.127), units of transfused RBCs (4 vs 2], P=0.152) or all-cause mortality (5.4% [2/37] vs 10% [4/41], P=0.518) were not statistically significant. Conclusion: This is the first description of three distinctly different fibrinolytic phenotypes in cardiac surgery patients. In this population, the use of AF was associated with increased morbidity.

Arushi Singh

and 6 more

Background: Ibrutinib is associated with atrial fibrillation (AF), though echocardiographic predictors of AF have not been studied in this population. We sought to determine whether left atrial (LA) strain on transthoracic echocardiography could identify patients at risk for developing ibrutinib-related atrial fibrillation (IRAF). Methods: We performed a retrospective review of 66 patients who had an echocardiogram prior to ibrutinib treatment. LA strain was measured with TOMTEC Imaging Systems, obtaining peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) on 4-chamber and 2-chamber views. Statistical analysis was performed with Chi-square analysis, T-test, or binomial regression analysis, with a p-value < 0.05 considered statistically significant. Results: Twenty-two patients developed IRAF (33%). Age at initiation of ibrutinib was significantly associated with IRAF (65.1 years vs. 74.1 years, p = 0.002). Mean ibrutinib dose was lower among patients who developed IRAF (388.2 ± 121.7 vs. 448.6 ± 88.4, p = 0.025). E/e’ was significantly higher among patients who developed IRAF (11.5 vs. 9.3, p = 0.04). PALS was significantly lower in patients who developed AF (30.3% vs. 36.3%, p = 0.01). On multivariate regression analysis, age, PALS and PACS were significantly associated with IRAF. On multivariate regression analysis, only PACS remained significantly associated with IRAF while accounting for age. Conclusions: Age, ibrutinib dose, E/e’, and PALS on pre-treatment echocardiogram were significantly associated with development of IRAF. On multivariate regression analyses, age, PALS and PACS remained significantly associated with IRAF. Impaired LA mechanics add to the assessment of patients at risk for IRAF

James Hummel

and 1 more

We thank Medina et al. for their interest in our recent work on QTc prolongation associated with treatment of COVID-19 patients with hydroxychloroquine and azithromycin. As they appropriately point out in their letter, genetic variation is likely a significant determinant of QT prolongation in the population at large and in COVID-19 patients specifically. While drugs causing acquired long QT syndrome and torsades de pointes are generally blockers of IKr, repolarization results from the aggregate of multiple inward and outward currents. Patients with sub-clinical defects in any of these ion channels can have normal or only slightly prolonged baseline QT intervals, but may possess decreased repolarization reserve leading to an exaggerated response to IKr blockade (1).  In our study, a baseline QTc of > 460 ms was associated with excessive QTc prolongation, and this likely represents a group of patients with sub-clinical cardiac ion channel mutations (so called “first hit”) (2). We also agree that many patients with latent mutations demonstrate a normal baseline QT, which gets prolonged with the addition of a drug or a change in the clinical condition “second hit” (3). The patients in our study who exhibited QTc prolongation were generally acutely ill, and displayed “multiple hits” that led to QTc prolongation and it is certainly plausible that many may have had sub-clinical cardiac ion mutations. We therefore wholeheartedly agree that pharmacogenetics should be considered in studies of drug-induced QT prolongation, however this information is rarely available to include for acutely ill patients. And while it makes sense to obtain genetic profiles prior to administration of QT-prolonging medications, that can only be performed in the elective outpatient setting, while taking into consideration medical, ethical and social issues related to asymptomatic genetic screening (e.g. cost, reimbursement, informed consent, etc…). There is significant interest in building genomic databases, and when this becomes a reality for the population at large we believe that genetic information should certainly be included in studies of QT prolongation.Roden DM Long QT syndrome: reduced repolarization reserve and the genetic link. J Intern Med. 2006 Jan; 259(1):59-69.Napolitano C, Schwartz PJ, Brown AM, et al. Evidence for a cardiac ion channel mutation underlying drug-induced QT prolongation and life-threatening arrhythmias. J Cardiovasc Electrophysiol. 2000;11:691–6Sauer AJ and Newton-Cheh C. Clinical and genetic determinants of torsade de pointes risk. Circulation. 2012;125:1684-94.

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