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Yun Zhang

and 12 more

ABSTRACT Background Exposed to house dust mite (HDM) is known to be associated with allergic asthma. Endoplasmic reticulum (ER) stress is involved in the regulation of mucus hyper secretion. However, the mechanism remains unclear. Our main goal was to investigate the relationship of TBK1 pathway regulates the expression of MUC5AC under the HDM induced ER stress promote allergic asthma. Methods Using HDM induced allergic mice and stimulated over expression of MUC5AC in human airway epithelial cells. We examined the mucus and the expression of ER stress markers both in vivo and in vitro. Additionally, we investigated whether TBK1, NF-κB, STAT6 play an important role in the HDM induced ER stress promote airway mucus hyper secretion. Results Mice exposed to HDM were identified ER stress, hyper secretion of mucus, and activated TBK1-NF-κB/STAT6 signaling pathway in airway epithelial cells of asthmatic mice. Similarly results had also been observed in the human airway epithelial cells after exposed to HDM. Both in vivo and in vitro study not only revealed that an anti-allergy drug, Amlexanox, reduced super response of mucus and weaken TBK1-NF-κB/STAT6 signal of induced asthma. But also indicated HDM induced ER stress result in over production of MUC5AC, which can be decreased by the inhibition of TBK1, NF-κB, STAT6, or even by using ER stress inhibitor 4-PBA, respectively. Conclusions Our results show that TBK1-NF-κB/STAT6 plays a pivotal role in the HDM induced ER stress result in over production of mucus protein MUC5AC in the asthmatic airway.

songkeat yodteerug

and 5 more

Background : Early repolarization pattern (ERP) is associated with long-term cardiovascular death. However, the incidence of early repolarization syndrome ( ERS) has never been studied in a general population-based cohort study. Purpose : To determine the prevalence and long-term outcome of ERP as well as the incidence of ERS in a general population-based cohort study. Methods : Participants from the electricity generating authority of Thailand (EGAT) study during 1997 to 2015 were included. The outcomes included cardiovascular death,deaths due to acute myocardial infarction, SCD, and all-cause mortality. A Cox- proportional hazard model was used to determine the association between ERP and the outcomes. Results: 2,689 participants with completed ECGs and risk factor profiles were included for the analysis. Mean follow up duration was 11.2±6.7 years. There were 444 participants with baseline ERP. There were 566 deaths during the follow-ups; of these, 21 were SCD including 6 ERS. The prevalence and incidence of ERS in our study was 0.22% and 0.20 per 1000 person-year. Overall, ERP was not associated with an increased risk of all-cause mortality (hazard ratio [HR]=1.04; 95% confidence interval [CI]:0.81 to 1.34; p =0.75). However, ERP was associated with an increased risk of all-cause mortality in the population ≤55 years old (HR=2.36; 95% CI:1.47-3.77; p <0.01). Conclusion : The prevalence of ERP in the Thai population was higher than the prevalence in other countries in Asia. Our study supports previous studies that ERP is associated with a long-term increased risk of all-cause mortality in the young-middle age population.

Chung Lin Lee

and 7 more

Yuan Ren

and 5 more

Objective To assess whether a full enhanced recovery after surgery (ERAS) program can further reduce perioperative outcomes among patients undergoing gynaecologic laparoscopic procedures relative to those undergoing limited ERAS management. Design Single-center, open-label, randomized trial. Setting A tertiary hospital, China: December 2018 to October 2019. Population One hundred and forty-four women scheduled for an elective simple gynaecologic laparoscopic surgery. Methods Patients were randomized into two groups: full ERAS intervention or limited ERAS management. Primary outcome Postoperative length of stay (LOS). Results Postoperative LOS for the full ERAS program showed a 1-day reduction in comparison to the limited ERAS group (median of 1.0 day versus 2.0 days, respectively; P = .002). Multivariate regression analysis identified preoperative carbohydrate loading and opioid-sparing analgesia as the independent factors for discharging on postoperative day (POD) 1. Patients in the full ERAS program reported less postoperative pain within 72 hours postoperatively and had a lower narcotic consumption rate compared with those in the limited ERAS management. They also enjoyed better and faster recovery as demonstrated by the QoR-15 scale on POD 3: median of 137.0 for full ERAS program versus 130.0 for limited ERAS management, respectively (P = .020). There were no significant differences between groups regarding postoperative complication rate, readmission rate, or in-hospital cost. Conclusion The addition of full ERAS management can further reduce postoperative length of stay and improve patients’ quality of life after laparoscopic surgery for gynaecologic diseases. Keywords enhanced recovery after surgery, perioperative management, gynaecologic laparoscopic surgery, length of stay.

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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.

Roberto CHIESA

and 3 more

During the first phase of COVID-19 pandemic in Italy, several strategies have been taken to deal with the pandemic outbreak. The Regional Authority of Lombardy remodeled the hospitalization system in order to allocate appropriate resources to treat COVID-19 patients and to identify “Hub/Spoke” hospitals for highly specialized medical activities. The Hubs hospitals were required to guarantee full time evaluation of all patients presenting with cardiovavascular diseases with an independent pathway for patients with suspect or confirmed COVID-19 infection. San Raffaele Hospital was identified as Hub for cardiovascular emergencies and the Vascular Surgery Department was remodeled to face this epidemic situation. Surgical treatment was reserved only to symptomatic, urgent or emergent cases. Large areas of the hospital were simultaneously reorganized to assist COVID-19 patients. During this period, 135 patients were referred to San Raffaele Vascular Surgery Department. COVID-19 was diagnosed in 24 patients and, among them, acute limb ischemia was the most common cause of admission. At this time, the COVID-19 trend is in decline in Italy and the local authorities reorganized the health care system in order to return to normal activities avoiding new escalations of COVID-19 cases. Several strategies have been taken to ensure the safety of the San Raffaele hospital, and maintaining potentially suspected patients with COVID-19 separated from other patients. The aim of this paper is to report the remodeling of the Vascular Surgery Department of San Raffaele Hospital as regards the strategies of preparation, escalation, de-escalation and return to normal activities during the COVID-19 pandemic.

Jose Lemus Calderon

and 5 more

INTRODUCTION: The SARS-CoV-2 coronavirus pandemic has caused more than fifteen million infections worldwide. Our aim is to investigate the differentiating characteristics in asthmatic patients with SARS-CoV-2 infection in the community of Castilla la Mancha. METHODS: We used the Savana® software and its algorithm based on Big Data and artificial intelligence, performed a retrospective search of the diagnoses of COVID 19 and asthma in the digitized medical records with positive RT-PCR results for SARS-CoV-2, and analysed the demographic characteristics, comorbidities, hospitalization data and deaths. RESULTS: 6,310 patients with positive RT-PCR for SARS-CoV-2 were selected, of which 577 had a diagnosis of asthma with a prevalence of 9.14%. The mean age in SARS-CoV-2 (SC2) was 59 ±19 years of age and in SARS-CoV2-asthma (SC2-A) 55 ±20 years of age. SC2 included 2983 (41%) men and 3327 (59%) women, while SC2-A included 198 (31%) men and 379 (69%) women. High blood pressure (BP) was the most common comorbidity in both groups (51%). 2,164 SC2 (34.2%) and 131 SC2-A (22.7%) required hospitalization with an asthma prevalence of 6.05%. 250 SC2 (3.96%) and 21 SC2-A (3.64%) died. CONCLUSION: The prevalence of asthma in our SARS-CoV-2 positive RT-PCR population was 9.14% and 6.05% in hospitalized patients. HBP is the most frequent comorbidity in both groups, and smoking is the only one with significant differences, more frequent in asthmatics. Mortality is lower in patients with asthma

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