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1.
K. Jessica Norberg Salvatore Nania Xuan Li Hui Gao Peter Szatmary Ralf Segersvärd Stephan Haas Annika Wagman Urban Arnelo Robert Sutton Rainer L. Heuchel J. Matthias Löhr 《Pancreatology》2018,18(7):734-741
Background
To date, there still is a lack of specific acute pancreatitis markers and specifically an early marker that can reliably predict disease severity. The inflammatory response in acute pancreatitis is mediated in part through oxidative stress and calcineurin-NFAT (Nuclear Factor of Activated T-cells) signaling, which is inducing its own negative regulator, regulator of calcineurin 1 (RCAN1). Caerulein induction is a commonly used in vivo model of experimental acute pancreatitis. Caerulein induces CN-NFAT signaling, reactive oxygen species and inflammation.Methods
To screen for potential markers of acute pancreatitis, we used the caerulein model of experimental acute pancreatitis (AP) in C57Bl/6?J mice. Pancreata from treated and control mice were used for expression profiling. Promising gene candidates were validated in cell culture experiments using primary murine acinar cells and rat AR42J cells. These candidates were then further tested for their usefulness as biomarkers in mouse and human plasma.Results
We identified a number of novel genes, including Regulator of calcineurin 1 (Rcan1) and Sestrin 2 (Sesn2) and demonstrated that they are induced by oxidative stress, by stimulation with H2O2 and by inhibiting caerulein stimulated expression with the antioxidant N-acetylcysteine. We found Rcan1 protein to be significantly elevated in AP-induced mouse plasma as well as in plasma from AP patients.Conclusion
We demonstrated that Rcan1 is regulated by oxidative stress and identified RCAN1 as a potential diagnostic marker of AP. 相似文献2.
Shuang Chen Kenichi Shimada Timothy R. Crother Ebru Erbay Prediman K. Shah Moshe Arditi 《Journal of the American College of Cardiology》2018,71(14):1553-1570
Background
Recent studies indicate that Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) signaling promote the development of high fat diet–induced atherosclerosis in hypercholesterolemic mice.Objectives
The authors investigated the role of TLR4/MyD88 signaling in hematopoietic and stromal cells in the development and infection-mediated acceleration of atherosclerosis.Methods
The authors generated bone marrow chimeras between wild-type and Tlr4–/– mice, as well as wild-type and Myd88–/– mice. All mice were on the Apoe–/– background and fed high fat diet. The authors infected the chimeric mice with C. pneumoniae (CP) and fed them high fat diet.Results
Aortic sinus plaques and lipid content were significantly reduced in Apoe–/– mice that received Tlr4–/–or Myd88–/– bone marrow compared with control animals despite similar cholesterol levels. Similarly, Tlr4 or Myd88 deficiency in stromal cells also led to a reduction in the lesion area and lipid in aortic sinus plaques. MyD88 expression only in CD11c+ dendritic cells (myeloid cells) in cells was sufficient in otherwise MyD88-deficient mice to induce CP infection–mediated acceleration of atherosclerosis, underlining the key role of MyD88 in CD11c+ dendritic cells (myeloid cells). Whereas CP infection markedly accelerated atherosclerosis in TLR4- or MyD88-positive chimeras, CP infection had a minimal effect on atherosclerosis in TLR4- or MyD88-deficient mice (either in the hematopoietic or stromal cell compartments).Conclusions
The authors show that both CP infection and metabolic stress associated with dyslipidemia use the same innate immune response pathway, utilizing TLR4/MyD88 signaling, with similar relative contributions in bone marrow–derived hematopoietic cells and in stromal cells. Further studies are required to understand this intricate and complex cross talk among innate and adaptive immune systems in various conditions to more effectively design dendritic cell–mediated atheroprotective vaccines and other therapeutic strategies. 相似文献3.
Yosuke Asada Mikiko Okano Waka Ishida Satoshi Iwamoto Ken Fukuda Toshiaki Hirakata Norihiro Tada Atsuki Fukushima Nobuyuki Ebihara Akira Kudo Akira Matsuda 《Allergology international》2019,68(2):233-239
Background
To investigate the potential roles of periostin (POSTN), an extracellular matrix preferentially expressed in Th2-skewed conditions in the pathophysiology of allergic conjunctivitis.Methods
The roles of POSTN in ragweed-induced experimental allergic conjunctivitis (RW-EAC) were evaluated using both POSTN-knockout (KO) and congenic BALB/c wild-type mice. Histological analysis was carried out to enumerate eosinophils/basophils in the conjunctival tissue. Th2 cytokine expression was evaluated by quantitative polymerase chain reaction (Q-PCR), and microarray analysis was performed to elucidate genes differentially expressed in POSTN-KO and wild-type mice in the RW-EAC model.Results
Upregulation of POSTN expression and eosinophil infiltration was observed in subconjunctival tissue of RW-EAC in the wild-type mice. The number of infiltrating eosinophils in the conjunctivae of RW-EAC was diminished in POSTN-KO mice compared to wild-type mice. Q-PCR analysis of conjunctival tissue showed induction of Th2 cytokine (Ccl5, Il4, Il5, Il13) expression in the RW-EAC and attenuated Ccl5, Il4, Il13 mRNA expression in the conjunctivae of the RW-EAC using POSTN-KO mice. Microarray analysis and immunohistochemical analysis showed diminished basophil marker (Mcpt8) expression and reduced numbers of infiltrating basophils in the conjunctivae of RW-EAC in POSTN-KO mice.Conclusions
POSTN expression in conjunctival tissue plays an indispensable role in the late-phase reaction of the RW-EAC model by facilitating eosinophil/basophil infiltration and augmenting Th2 cytokine expression. 相似文献4.
Andrea Párniczky Maisam Abu-El-Haija Sohail Husain Mark Lowe Grzegorz Oracz Miklós Sahin-Tóth Flóra K. Szabó Aliye Uc Michael Wilschanski Heiko Witt László Czakó Tassos Grammatikopoulos Ib Christian Rasmussen Robert Sutton Péter Hegyi 《Pancreatology》2018,18(2):146-160
Background
Pediatric pancreatitis is an underdiagnosed disease with variable etiology. In the past 10–15 years the incidence of pediatric pancreatitis has increased, it is now 3.6–13.3 cases per 100,000 children. Up-to-date evidence based management guidelines are lacking for the pediatric pancreatitis. The European Pancreatic Club, in collaboration with the Hungarian Pancreatic Study Group organized a consensus guideline meeting on the diagnosis and management of pancreatitis in the pediatric population.Methods
Pediatric Pancreatitis was divided into three main clinical categories: acute pancreatitis, acute recurrent pancreatitis and chronic pancreatitis. Fifteen relevant topics (acute pancreatitis: diagnosis; etiology; prognosis; imaging; complications; therapy; biliary tract management; acute recurrent pancreatitis: diagnosis; chronic pancreatitis: diagnosis, etiology, treatment, imaging, intervention, pain, complications; enzyme replacement) were defined. Ten experts from the USA and Europe reviewed and summarized the available literature. Evidence was classified according to the GRADE classification system.Results
Within fifteen topics, forty-seven relevant clinical questions were defined. The draft of the updated guideline was presented and discussed at the consensus meeting held during the 49th Meeting of European Pancreatic Club, in Budapest, on July 1, 2017.Conclusions
These evidence-based guidelines provides the current state of the art of the diagnosis and management of pediatric pancreatitis. 相似文献5.
David Adlam Timothy M. Olson Nicolas Combaret Jason C. Kovacic Siiri E. Iismaa Abtehale Al-Hussaini Megan M. O&#x;Byrne Sara Bouajila Adrien Georges Ketan Mishra Peter S. Braund Valentina d’Escamard Siying Huang Marios Margaritis Christopher P. Nelson Mariza de Andrade Daniella Kadian-Dodov Catherine A. Welch Nabila Bouatia-Naji 《Journal of the American College of Cardiology》2019,73(1):58-66
Background
Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene.Objectives
This study sought to test the association between the rs9349379 genotype and SCAD.Methods
Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD.Results
The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence.Conclusions
The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD. 相似文献6.
Mohannad Abou Saleh Vijit Chouhan Emad Mansoor Dharani Guttikonda Ashwinee Natu Michael Enzerra Raj Paspulati David Ngendahimana Bayan Alsuleiman Lorna Kang Brooke Glessing Amitabh Chak Tyler Stevens Peter J. Lee 《Pancreatology》2019,19(1):163-168
Background/objectives
Severity classification systems of acute pancreatitis (AP) assess inpatient morbidity and mortality without predicting outpatient course of AP. To provide appropriate outpatient care, determinants of long-term prognosis must also be identified. The aim of this study was to define clinical groups that carry long-term prognostic significance in AP.Methods
A retrospective study that included patients admitted with AP was conducted. Determinants of long-term prognosis were extracted: These included Revised Atlanta and Determinant Based Classification (RAC), Charlson Comorbidity Index (CCI), Modified CT Severity Index (MCTSI), etiology, and local complications (LCs). Seven surrogates of morbidity up to 1 year after discharge were also collected and subsequently imputed into a clustering algorithm. The algorithm was set to produce three categories and multinomial regression analysis was performed.Results
281 patients were included. The incidences of morbidity endpoints were similar among the 3 RAC categories. Three clusters were identified that carried long-term prognostic significance. Each cluster was given a name to reflect prognosis. The limited AP had the best prognosis and included patients without LCs with a low co-morbidity burden. The brittle AP had a low co-morbidity burden and high MCTSI (LCs 94%). It ran a very morbid course but had excellent survival. The high-risk AP had the worst prognosis with the highest mortality rate (28%). They had a high co-morbidity burden without local complications.Conclusion
Categories that carry long-term prognostic significance in AP have been developed. This study could help formulate appropriate follow-up and ultimately improve AP outcomes. 相似文献7.
Yongzhi Zhai Lu Gan Sai Huang Qinrui Xing Xuan Zhou Lili Wang Cong Feng Li Chen Tanshi Li 《Pancreatology》2019,19(1):158-162
Objectives
To study the therapeutic effect of early peripancreatic lavage of ulinastatin on severe acute pancreatitis(SAP).Methods
Sixteen pigs were divided into 4 groups: model(SAP), saline lavage(SL), ulinastatin lavage(UL), intravenous ulinastatin(IU). UL and SL group were given peripancreatic lavage of ulinastatin by ultrasound-guided perirenal catheterization and IU group was intravenously instilled with ulinastatin. The multi-organ functions and the inflammatory factors were observed.Results
UL group has the best therapeutic effect. The changes of multi-organ functions and the inflammatory factors were compared with SAP group as follows. In time window of treatment: amylase (p?<?0.01), lipase (p?<?0.01), ALT (p?>?0.05), AST (p?<?0.05), CR (p?<?0.01), UR (p?<?0.01), IL-6 (p?<?0.01), IL-10 (p?<?0.01). In post-treatment phase: amylase (p?<?0.01), lipase (p?<?0.01), ALT (p?<?0.01), AST (p?<?0.01), CR (p?<?0.05), UR (p?>?0.05), IL-6 (p?<?0.01), IL-10 (p?<?0.01).Conclusions
Early peripancreatic lavage of ulinastatin in SAP could effectively improve the multi-organ functions and inflammatory response. 相似文献8.
Wei Shuai Bin Kong Hui Fu Caijie Shen Xiaobo Jiang He Huang 《The Canadian journal of cardiology》2019,35(2):208-216
Background
Myeloid differentiation protein 1 (MD1) is expressed in various tissues, including the heart. However, the role of MD1 in obesity-related atrial remodelling remains incompletely understood. Here, this study intends to determine the regulatory role and underlying mechanisms of MD1 in obesity-related atrial remodelling.Methods
A high-fat diet (HFD) feeding was performed in 6-week-old MD1-knockout (MD1-KO) mice and wild-type (WT) littermates for 20 weeks. Morphological, biochemical, functional, histological, and electrophysiological studies were conducted at the age of 26 weeks.Results
Our results revealed that the MD1 expression levels were downregulated in the atrium of the HFD-fed induced obesity mice. An increase in body weight, glucose intolerance, hyperlipidemia, and adverse atrial remodelling, such as atrial in?ammation and fibrosis, were induced by HFD feeding in WT mice. Vulnerability to atrial fibrillation (AF) was also significantly increased by HFD feeding in WT mice. In addition, these adverse effects caused by HFD-fed induced obesity were further exaggerated in MD1-KO mice compared with WT mice. Mechanistically, MD1-KO activated TLR4/NF-κB signaling pathways, which led to atrial remodelling in mice fed by HFD by increasing the phosphorylation of p65 and IκBα.Conclusions
Our data suggested that MD1 deficiency played an important role in accelerating the development of in?ammatory atrial fibrosis and increasing vulnerability to AF in mice with HFD-fed induced obesity, providing an essential target for improving HFD-induced atrial remodelling. 相似文献9.
Robbert A. Hollemans Nora D.L. Hallensleben David J. Mager Johannes C. Kelder Marc G. Besselink Marco J. Bruno Robert C. Verdonk Hjalmar C. van Santvoort 《Pancreatology》2018,18(3):253-262
Objectives
This study systematically explores the prevalence of pancreatic exocrine insufficiency (PEI) after acute pancreatitis in different subgroups of etiology (biliary/alcoholic/other), disease severity and follow-up time (<12, 12–36 and?>?36 months after index admission).Methods
PubMed and EMBASE databases were searched, 32 studies were included in this study level meta-analysis.Results
In a total of 1495 patients with acute pancreatitis, tested at a mean of 36 months after index admission, the pooled prevalence of PEI was 27.1% (95%-confidence interval [CI]: 20.3%–35.1%). Patients from seven studies (n?=?194) underwent direct tests with pooled prevalence of 41.7% [18.5%–69.2%]. Patients from 26 studies (n?=?1305) underwent indirect tests with pooled prevalence of 24.4% [18.3%–31.8%]. In subgroup analyses on patients that underwent fecal elastase-1 tests, PEI occurred more often in alcoholic pancreatitis (22.7% [16.6%–30.1%]) than in biliary pancreatitis (10.2% [6.2%–16.4%]) or other etiology (13.4% [7.7%–22.4%]; P?=?0.02). Pooled prevalence of PEI after mild and severe pancreatitis was 19.4% [8.6%–38.2%] and 33.4% [22.6%–46.3%] respectively in studies using fecal elaste-1 tests (P?=?0.049). Similar results were seen in patients without (18.9% [9.3%–34.6%]) and with necrotizing pancreatitis (32.0% [18.2%–49.8%]; P?=?0.053). Over time, the prevalence of PEI decreased in patients who underwent the fecal elastase-1 test and increased in patients who underwent the fecal fat analysis.Conclusions
After acute pancreatitis, a quarter of all patients develop PEI during follow-up. Alcoholic etiology and severe and necrotizing pancreatitis are associated with higher risk of PEI. The prevalence of PEI may change as time of follow-up increases. 相似文献10.
Jolanta Jaworek Joanna Szklarczyk Michalina Kot Marta Góralska Andrzej Jaworek Joanna Bonior Anna Leja-Szpak Katarzyna Nawrot-Porąbka Paweł Link-Lenczowski Piotr Ceranowicz Krystyna Galazka Zygmunt Warzecha Artur Dembinski Piotr Pierzchalski 《Pancreatology》2019,19(3):401-408
Objective
Chemerin, an adipokine, works as the chemoattractant for the immune cells. The role of chemerin in the inflammatory reaction is controversial. Chemerin has been shown to aggravate the inflammatory response, but other studies demonstrated its anti-inflammatory influence. This study assessed the effects of chemerin on acute pancreatitis (AP) in vivo and in vitro.Methods
For in vivo experiments male Wistar rats were used. For in vitro study rat pancreatic AR42J cells were employed. Chemerin (1, 5 or 10?μg/kg) was given to the rats prior to the induction of AP by subcutaneous caerulein infusion (25?μg/kg). For in vitro studies cells were subjected to caerulein (10?nM) with or without chemerin (100?nM). Serum amylase activity was measured by enzymatic method, serum TNFα concentration - by ELISA kit. Western-blot was used to examine cellular proteins.Results
AP was confirmed by histological examination. Chemerin given to AP rats decreased histological manifestations of AP, reduced serum amylase activity and TNFα concentration. In AR42J cells subjected to caerulein with addition of chemerin signal for TNFα was reduced comparing to the cultures treated with caerulein alone. Analysis of the dynamics of nuclear translocation for p50, p65 and Bcl-3 points out to NF-κB attenuation as a mechanism of observed anti-inflammatory action of chemerin.Conclusion
Chemerin significantly alleviated severity of AP in the rat, this is possibly due to the inhibition of pro-inflammatory signaling in the pancreatic cells. 相似文献11.
Arash Salemi Art Sedrakyan Jialin Mao Adham Elmously Harindra Wijeysundera Derrick Y. Tam Antonino Di Franco Simon Redwood Leonard N. Girardi Stephen E. Fremes Mario Gaudino 《JACC: Cardiovascular Interventions》2019,12(1):90-97
Objectives
The aim of this study was to assess the impact of individual operator experience on transfemoral transcatheter aortic valve replacement (TAVR) outcomes.Background
TAVR volume-outcome relationships have not been evaluated at the individual operator level.Methods
New York Statewide Planning and Research Cooperative System data from 8,771 transfemoral TAVR procedures performed by 207 operators between 2012 and 2016 were analyzed. Operator volume was defined as the number of TAVR procedures performed during 1 year prior to the index procedure. Hierarchical and restrictive cubic spline regression models were used to evaluate the impact of individual operator experience on risk-adjusted in-hospital outcomes. The primary outcome was a composite of in-hospital mortality, stroke, and/or acute myocardial infarction. Secondary outcomes were the individual components of the primary outcome.Results
After adjusting for hospital and physician characteristics, patients undergoing TAVR performed by high-volume physicians (≥80/year) had a significantly lower risk for death, stroke, or acute myocardial infarction (odds ratio: 0.59; 95% confidence interval: 0.37 to 0.93) compared with those treated by low-volume physicians (<24/year). Being treated by operators who performed 200 procedures during the prior year was associated with significantly lower risks for post-procedural stroke (odds ratio: 0.41; 95% confidence interval: 0.17 to 0.97) and composite events (odds ratio: 0.45; 95% confidence interval: 0.26 to 0.78). This relationship was nonlinear, and a sensitivity analysis excluding the first 10, 20, and 30 procedures for each operator mitigated the effect of the initial learning curve.Conclusions
Increased TAVR experience of operators is associated with improved risk-adjusted in-hospital outcomes. These results have potentially important implications for individual training and hospital programs in TAVR. 相似文献12.
Takenori Haruna Shin Kariya Tazuko Fujiwara Atsushi Yuta Takaya Higaki Pengfei Zhao Yukiko Ogawa Kengo Kanai Yuji Hirata Aiko Oka Kazunori Nishizaki Mitsuhiro Okano 《Allergology international》2019,68(1):82-89
Background
The development of methods to predict the clinical effectiveness of sublingual immunotherapy (SLIT) for allergic diseases is a crucial matter. We sought to determine whether whole saliva, which is the first body component that contacts allergen extracts during SLIT, is associated with the clinical effectiveness of SLIT in Japanese cedar pollinosis.Methods
Blood monocytes or monocytic THP-1 cells were cultured in the presence or absence of either whole saliva or pure saliva with or without treatments including filtration and blockade of TLR2 and/or TLR4 signaling. IL-10 levels in the supernatants were then measured. Whole saliva-induced IL-10 production by THP-1 cells was compared between asymptomatic and disease-onset patients during peak pollen dispersal after SLIT.Results
Both monocytes and THP-1 cells produced substantial amounts of IL-10 in response to whole saliva. IL-10 production was significantly reduced in response to pure saliva and 0.2 μm-filtered saliva. Simultaneous treatment with polymyxin B and TL2.1, a neutralizing antibody against TLR2, also reduced IL-10 production. IL-10 levels produced by THP-1 cells in response to whole saliva collected prior to SLIT were significantly higher in asymptomatic patients determined by symptom-medication scores than disease-onset patients following SLIT. Such differences were not seen in saliva collected 3 months after the initiation of SLIT or saliva collected during peak pollen dispersal.Conclusions
Our results provide a basis for why the sublingual route is effective and preferable in allergen immunotherapy. Saliva-induced IL-10 levels produced by THP-1 cells may be a predictive marker for clinical remission after SLIT. 相似文献13.
Yohei Nakashima Takao Ohtsuka So Nakamura Yasuhisa Mori Kohei Nakata Yoshihiro Miyasaka Kosei Ishigami Ryota Matsuda Yoshinao Oda Masafumi Nakamura 《Pancreatology》2019,19(1):50-56
Background/objectives
The biological features of cystic pancreatic neuroendocrine tumors (PNETs) remain unclear. The aim of this study was to clarify the clinicopathological characteristics of non-functioning PNETs (NF-PNETs) with a cystic component.Methods
The medical records of 75 patients with NF-PNETs who had undergone resection in our institution were retrospectively reviewed. Clinicopathological factors were compared between PNETs with and without a cystic component. Expression of somatostatin 2 receptor (SSTR-2) was also analyzed.Results
Cystic PNETs were diagnosed in 14 patients (19%). The proportion of men was significantly higher for cystic than solid PNETs (79% vs. 44%, P?<?0.05) and cystic PNETs were significantly larger than solid PNETs (25?mm vs. 17?mm, P?<?0.01). However, there were no significant differences in the prevalence of lymph node metastases (14% vs. 10%, P?=?0.64), hepatic metastasis (7% vs. 3%, P?=?0.54), or disease-free survival rate (both 86%, P?=?0.29) between PNETs with and without a cystic component. SSTR-2 expression was more frequently observed in PNETs with a cystic component than in those without (100% vs. 70%, P?<?0.01).Conclusions
Although cystic PNETs were larger upon diagnosis than solid PNETs in this study, prognosis after surgical resection did not differ significantly between these types of PNET. Somatostatin receptor scintigraphy and somatostatin analogues may be more useful for diagnosing and treating cystic PNETs, respectively. 相似文献14.
Michael Frank Salma Adham Stéphanie Seigle Anne Legrand Tristan Mirault Pierrick Henneton Juliette Albuisson Nicolas Denarié Jean-Michaël Mazzella Elie Mousseaux Emmanuel Messas Pierre Boutouyrie Xavier Jeunemaitre 《Journal of the American College of Cardiology》2019,73(15):1948-1957
Background
Vascular Ehlers-Danlos syndrome (vEDS) is a rare genetic connective tissue disorder secondary to pathogenic variants within the COL3A1 gene, resulting in exceptional arterial and organ fragility and premature death. The only published clinical trial to date demonstrated the benefit of celiprolol on arterial morbimortality.Objectives
The authors herein describe the outcomes of a large cohort of vEDS patients followed ≤17 years in a single national referral center.Methods
All patients with molecularly confirmed vEDS were included in a retrospective cohort study. After an initial work-up, patients were treated or recommended for treatment with celiprolol (≤400 mg/day) in addition to usual care and scheduled for yearly follow-up. vEDS-related events and deaths were collected and recorded for each patient.Results
Between 2000 and 2017, 144 patients (median age at diagnosis 34.5 years, 91 probands) were included in this study. After a median follow-up of 5.3 years, overall patient survival was high (71.6%; 95% confidence interval: 50% to 90%) and dependent on the type of COL3A1 variant, age at diagnosis, and medical treatment. At the end of the study period, almost all patients (90.3%) were treated with celiprolol alone or in combination. More than two-thirds of patients remained clinically silent, despite a large number (51%) with previous arterial events or arterial lesions at molecular diagnosis. Patients treated with celiprolol had a better survival than others (p = 0.0004). The observed reduction in mortality was dose-dependent: the best protection was observed at the dose of 400 mg/day versus <400 mg/day (p = 0.003). During the period surveyed, the authors observed a statistically significant difference in the ratio of hospitalizations for acute arterial events/hospitalizations for regular follow-up before and after 2011.Conclusions
In this long-term survey, vEDS patients exhibited a low annual occurrence of arterial complications and a high survival rate, on which the overall medical care seems to have a positive influence. 相似文献15.
Michael Szarek Harvey D. White Gregory G. Schwartz Marco Alings Deepak L. Bhatt Vera A. Bittner Chern-En Chiang Rafael Diaz Jay M. Edelberg Shaun G. Goodman Corinne Hanotin Robert A. Harrington J. Wouter Jukema Takeshi Kimura Robert Gabor Kiss Guillaume Lecorps Kenneth W. Mahaffey Angèle Moryusef Ph. Gabriel Steg 《Journal of the American College of Cardiology》2019,73(4):387-396
Background
The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial compared alirocumab with placebo, added to high-intensity or maximum-tolerated statin treatment, after acute coronary syndrome (ACS) in 18,924 patients. Alirocumab reduced the first occurrence of the primary composite endpoint and was associated with fewer all-cause deaths.Objectives
This pre-specified analysis determined the extent to which alirocumab reduced total (first and subsequent) nonfatal cardiovascular events and all-cause deaths in ODYSSEY OUTCOMES.Methods
Hazard functions for total nonfatal cardiovascular events (myocardial infarction, stroke, ischemia-driven coronary revascularization, and hospitalization for unstable angina or heart failure) and death were jointly estimated, linked by a shared frailty accounting for patient risk heterogeneity and correlated within-patient nonfatal events. An association parameter also quantified the strength of the linkage between risk of nonfatal events and death. The model provides accurate relative estimates of nonfatal event risk if nonfatal events are associated with increased risk for death.Results
With 3,064 first and 5,425 total events, 190 fewer first and 385 fewer total nonfatal cardiovascular events or deaths were observed with alirocumab compared with placebo. Alirocumab reduced total nonfatal cardiovascular events (hazard ratio: 0.87; 95% confidence interval: 0.82 to 0.93) and death (hazard ratio: 0.83; 95% confidence interval: 0.71 to 0.97) in the presence of a strong association between nonfatal and fatal event risk.Conclusions
In patients with ACS, the total number of nonfatal cardiovascular events and deaths prevented with alirocumab was twice the number of first events prevented. Consequently, total event reduction is a more comprehensive metric to capture the totality of alirocumab clinical efficacy after ACS. 相似文献16.
Chun Shing Kwok Binita Shah Jassim Al-Suwaidi David L. Fischman Lene Holmvang Chadi Alraies Rodrigo Bagur Vinayak Nagaraja Muhammad Rashid Mohamed Mohamed Glen P. Martin Evan Kontopantelis Tim Kinnaird Mamas Mamas 《JACC: Cardiovascular Interventions》2019,12(8):734-748
Objectives
The aim of this study was to describe the rates and causes of unplanned readmissions at different time periods following percutaneous coronary intervention (PCI).Background
The rates and causes of readmission at different time periods after PCI remain incompletely elucidated.Methods
Patients undergoing PCI between 2010 and 2014 in the U.S. Nationwide Readmission Database were evaluated for the rates, causes, predictors, and costs of unplanned readmission between 0 and 7 days, 8 and 30 days, 31 and 90 days, and 91 and 180 days after index discharge.Results
This analysis included 2,412,000 patients; 2.5% were readmitted between 0 and 7 days, 7.6% between 8 and 30 days, 8.9% between 31 and 90 days, and 8.0% between 91 and 180 days (cumulative rates 2.5%, 9.9%, 18.0%, and 24.8%, respectively). The majority of readmissions during each time period were due to noncardiac causes (53.1% to 59.6%). Nonspecific chest pain was the most common identifiable noncardiac cause for readmission during each time period (14.2% to 22.7% of noncardiac readmissions). Coronary artery disease including angina was the most common cardiac cause for readmission during each time period (37.4% to 39.3% of cardiac readmissions). The second most common cardiac cause for readmission was acute myocardial infarction between 0 and 7 days (27.6% of cardiac readmissions) and heart failure during all subsequent time periods (22.2% to 23.7% of cardiac readmissions).Conclusions
Approximately 25% of patients following PCI have unplanned readmissions within 6 months. Causes of readmission depend on the timing at which they are assessed, with noncardiovascular causes becoming more important at longer time points. 相似文献17.
Hirotoshi Ishiwatari Junya Sato Shinya Fujie Keiko Sasaki Junichi Kaneko Tatsunori Satoh Hiroyuki Matsubayashi Yoshihiro Kishida Masao Yoshida Sayo Ito Noboru Kawata Kenichiro Imai Naomi Kakushima Kohei Takizawa Kinichi Hotta Hiroyuki Ono 《Pancreatology》2019,19(1):191-195
Background/objectives
A clear criterion for terminating endoscopic ultrasound fine needle aspiration (EUS-FNA) without rapid on-site evaluation (ROSE) has not been established. However, a possible solution includes gross visual inspection (GVI) of the sample obtained with EUS-FNA. We performed a retrospective study to elucidate the efficacy of GVI for the diagnostic yield of EUS-FNA.Methods
Patients who underwent EUS-FNA of a pancreatic mass using a standard 22-G needle from January 2017 to December 2017 were included in the study. At least two punctures were performed for each patient, and GVI was performed for each pass by endoscopists. The correlation between GVI and pathological findings were investigated per needle pass for the first two passes. Regarding GVI, we evaluated the presence of a visible core (with or without) and the sample quantity (large or small).Results
We evaluated 126 EUS-FNA specimens and analyzed 252 needle passes. A final diagnosis of malignancy was made for 119 patients (94%). Accuracy rates were 92.5% with a visible core and 70.0% without a visible core (p?<?0.01), and 85.2% for large sample quantities and 70.2% for small sample quantities (p?<?0.01). Univariate analysis indicated that the presence of a visible core and large sample quantity were associated with accuracy. Multivariate analysis indicated that only the presence of a visible core was significant.Conclusions
GVI can predict the correct diagnosis when ROSE is unavailable. Evaluating the presence of a visible core is more sensitive than assessing the quantity of the sample obtained. 相似文献18.
Ali Gheysarzadeh Amir Ansari Mohammad Hassan Emami Amirnader Emami Razavi Mohammad Reza Mofid 《Pancreatology》2019,19(3):429-435
Background
Low-density lipoprotein receptor-Related Protein-1 (LRP-1) has been reported to involve in tumor development. However, its role in pancreatic cancer has not been elucidated. The present study was designed to evaluate the expression of LRP-1 in Pancreatic Ductal Adenocarcinoma Cancer (PDAC) as well as its association with prognosis.Methods
Here, 478 pancreatic cancers were screened for suitable primary PDAC tumors. The samples were analyzed using qRT-PCR, western blotting, and Immunohistochemistry (IHC) staining as well as LRP-1 expression in association with clinicopathological features.Results
The relative LRP-1 mRNA expression was up-regulated in 82.3% (42/51) of the PDAC tumors and its expression (3.72?±?1.25) was significantly higher than that in pancreatic normal margins (1.0?±?0.23, P?<?0.05). This up-regulation was stage dependent (P?<?0.05). A similar pattern of LRP-1 protein expression was discovered (P?<?0.05). The high expression of LRP-1 in the PDAC tissues was strongly correlated with the low survival time (P?=?0.001), TNM classification (P?=?0.001), low differentiations status (P?=?0.001), lymphatic invasion (P?=?0.01) and Perineural Invasion (PNI) status (P?=?0.001).Conclusions
Our finding for the first time revealed that LRP-1 expression inversely associated with poor prognosis and PNI in PDAC tumor. 相似文献19.
P. Kadermuneer R. Sandeep Vellani Haridasan Biju George Chakanalil Govindan Sajeev Mangalath Narayanan Krishnan 《Indian heart journal》2019,71(1):1-6
Background
Carotid sinus syndrome accounts for one third of patients who presents with unexplained syncope. Prevalence of carotid sinus hypersensitivity (CSH) in Indians has not been studied till now.Objectives
To assess the prevalence and associations of CSH in symptomatic patients above 50 years and to study its prognostic significance pertaining to sudden cardiac death, syncope, recurrent pre syncope and falls on 1 year follow up.Methods
Patients above 50 years who presented with unexplained syncope, recurrent syncope or falls were considered cases and those without these symptoms were considered as controls. All the patients underwent carotid sinus massage and their responses noted. All symptomatic patients were followed up and observed for events like sudden cardiac death, syncope, recurrent pre syncope and falls during 1 year follow up. Patients with recurrent syncope and predominant cardioinhibitory syncope were advised permanent pacemaker implantation.Results
A total of 252 patients were screened, 130 patients constituted cases and 49 patients constituted controls. CSH was demonstrable in 32% (n = 42) of cases as compared to 8% (n = 4) in controls (p < 0.001). Cardioinhibitory response was the predominant response (88%, n = 38) followed by mixed response (12%, n = 4). CSH was associated with advancing age, male gender (93%, n = 39, p < 0.001) and history of smoking (63%, n = 27, p = 0.009). Composite outcomes of sudden cardiac death, syncope, recurrent pre syncope and falls were significantly higher in patients with symptomatic CSH than in those without it (45%, n = 16 vs. 6.8%, n = 6; p < 0.001).Conclusions
In conclusion, the prevalence of CSH in patients above 50 yrs with unexplained syncope was high in our population. Patients with CSH and baseline symptoms developed recurrent syncope during follow up. Carotid sinus massage should be a part of routine examination protocol for unexplained syncope. 相似文献20.
Ali Alawieh Jan Vargas Kyle M. Fargen E. Farris Langley Robert M. Starke Reade De Leacy Rano Chatterjee Ansaar Rai Travis Dumont Peter Kan David McCarthy Fábio A. Nascimento Jasmeet Singh Lukas Vilella Aquilla Turk Alejandro M. Spiotta 《Journal of the American College of Cardiology》2019,73(8):879-890