bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of ACEi/ARB Use and Clinical Outcomes of COVID-19 Patients With Hypertension
Authors: Ma Jing , Shi Xiaowei , Yu Jiong , Lv Feifei , Wu Jian , Sheng Xinyu , Pan Qiaoling , Yang Jinfeng , Cao Hongcui , Li Lanjuan 
Published: May 2021

Objectives: Evidence has shown that angiotensin-converting enzyme 2 (ACE2), which can be upregulated after angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, may play a dual role in the pathogenesis and progression of coronavirus disease 2019 (COVID-19). We aimed to assess the association between the use of ACEi/ARB and the outcome of COVID-19 patients with preexisting hypertension in non-endemic areas.Methods: From January 17, 2020, to February 19, 2020, 286 patients with hypertension were enrolled in this retrospective study out of 1,437 COVID-19 patients from 47 centers in Zhejiang and Jiangsu Province. The composite endpoints consisted of mechanical ventilation, intensive care unit (ICU) admission, or death. Cox proportional hazards analysis was performed to assess the association between ACEi/ARB and clinical outcomes of COVID-19 patients with hypertension.Results: In the main analysis, 103 patients receiving ACEi/ARB were compared with 173 patients receiving other regimens. Overall, 44 patients (15.94%) had an endpoint event. The risk probability of crude endpoints in the ACEi/ARB group (12.62%) was lower than that in the non-ACEi/ARB group (17.92%). After adjusting for confounding factors by inverse probability weighting, the results showed that the use of ACEi/ARB reduced the occurrence of end events by 47% [hazard ratio (HR) = 0.53; 95% CI, 0.34–0.83]. Similar results were obtained in multiple sensitivity analyses.Conclusions: In this retrospective study, among COVID-19 patients with hypertension, the use of ACEi/ARB is not associated with an increased risk of disease severity compared with patients without ACEi/ARB. The trends of beneficial effects of ACEi/ARB need to be further evaluated in randomized clinical trials.
Case Report: Multimodality Imaging as a Lifeline for Fatal Localization of Valsalva Sinus Fibroelastoma
Authors: Tadic Snezana , Ilic Aleksandra , Stefanovic Maja , Stojsic-Milosavljevic Anastazija , Popov Tanja , Bjelobrk Marija , Milovancev Aleksandra , Maksimovic Nebojsa , Drid Patrik 
Published: May 2021

Background: Papillary fibroelastomas are rare benign heart tumors, and is most likely to involve the cardiac valves. We will present an extremely rare localization of a large Valsalva sinus fibroelastoma, with occasional left coronary artery ostial obstruction presented as an acute coronary syndrome. The tumor was removed surgically and histologically confirmed as papillary fibroelastoma. This review points to the crucial importance of multidisciplinary team decision and multimodality imaging methods for diagnosing the fibroelastoma, determination of size, and localization, which avoided complications of fatal embolization during an invasive procedure.Case Summary: A healthy 55-year-old male with vigorous physical daily training and exercise was admitted to the acute coronary syndrome emergency department. Shortly after admission, expert transthoracic echocardiography was performed. Computed tomography of the chest observed a large irregular hypodense tumor-like lesion in the bulbar aorta that was occasionally prolapsing into the left main coronary artery ostium and which corresponded to fibroelastoma. A few hours after admission, an emergency cardiac surgery was performed with the excision of a Valsalva sinus tumor (size 2 × 2 cm) located between the right and left coronary cusp of the aortic valve.Conclusions: Focus cardiac ultrasound should be performed for any acute coronary syndrome because of the possible Valsalva sinus fibroelastoma etiology. Its localization next to the left main coronary artery ostium is rare, and dangerous. The timely diagnosis can be made by the multimodality imaging method, however, the final diagnosis will be made pathohistologically. Early cardiac surgery may be a necessitated recourse for these patients in order to prevent a fatal outcome.
Ultra-Long GnRH Agonist Protocol During IVF/ICSI Improves Pregnancy Outcomes in Women With Adenomyosis: A Retrospective Cohort Study
Authors: Lan Jie , Wu Yaoqiu , Wu Zexuan , Wu Yingchen , Yang Rong , Liu Ying , Lin Haiyan , Jiao Xuedan , Zhang Qingxue 
Published: May 2021

ObjectiveThis study aimed to compare the ultra-long gonadotropin-releasing hormone agonist (GnRH-a) protocol and the long GnRH-a protocol during in vitro fertilization (IVF) or intracytoplasmic sperm (ICSI) treatment on fertility outcomes in women with adenomyosis.Materials and MethodsThis study was a retrospective cohort study. From January 2011 to May 2018, a total of 371 fresh IVF/ICSI cycles were included. Among the cycles included, 237 cycles of 212 women underwent the ultra-long GnRH-a protocol, while 134 cycles of 116 women underwent the long GnRH-a protocol. The rates of implantation, clinical pregnancy per embryo transfer, live birth, and early miscarriage were estimated between the compared protocols.ResultsIn the study, the early miscarriage rate in women undergoing the ultra-long GnRH-a protocol was significantly lower than those undergoing the long GnRH-a protocol (12.0% versus 26.5%, p = 0.045), whereas the differences in the rates of biochemical pregnancy, implantation, clinical pregnancy, and live birth in women between the two groups showed no statistical significance. The pregnancy outcomes were also sub-analyzed according to the adenomyotic region (diffuse and focal). As for diffuse adenomyosis, the rates of clinical pregnancy and live birth in women undergoing the ultra-long GnRH-a protocol were significantly higher than those undergoing the long GnRH-a protocol (55.3% versus 37.9%, p = 0.025; 43.4% versus 25.9%, p = 0.019, respectively). However, pregnancy outcomes showed no difference between the two protocols in women with focal adenomyosis.ConclusionsThe ultra-long GnRH-a protocol during IVF/ICSI improves pregnancy outcomes in women with adenomyosis, especially in women with diffuse adenomyosis when compared with the long GnRH-a protocol.
A Retrospective Study Comparison Between Stenting and Standardized Medical Treatment for Intracranial Vertebrobasilar Stenosis in a Real-World Chinese Cohort
Authors: Li Guanzeng , Yan Peng , Zhao Yuanyuan , Li Shan , Xue Yuan , Xiang Yuanyuan , Liu Xiaohui , Li Jifeng , Sun Qinjian 
Published: May 2021

Background: To date, there has been no consensus regarding the benefits of percutaneous transluminal angioplasty and stenting (PTAS) vs. those of standardized medical treatment (SMT) for patients with symptomatic intracranial vertebrobasilar stenosis (IVBS). The purpose of this retrospective study was to compare the effects of PTAS or SMT on symptomatic IVBS in a real-world Chinese population.Methods: We included 238 patients with ischemic stroke caused by IVBS stenosis who were admitted to Shandong Provincial Hospital Affiliated to Shandong University between September 2012 and May 2018; 62 of these patients were treated with SMT and 176 underwent PTAS. Ischemic stroke in the territory of the responsible artery, hemorrhage, and death within 1 year were recorded as primary endpoints. Secondary endpoints included assessment of stroke severity and the incidence of re-stenosis. The primary endpoint rates were compared between the PTAS and SMT groups at 7 days, 1, 6 months, and 1 year.Results: In the PTAS group, the success rate of stent placement was 98.9%. During the entire trial, except for 7 days, the SMT group had a higher frequency of primary endpoint events than did the PTAS group. The primary endpoint was 17.7% (11/62) vs. 8.6% (15/174) at 1 month (p = 0.049), 29% (18/62) vs. 14.4% (25/174) at 6 months (p = 0.01), and 32.2% (20/62) vs. 17.2% (30/174) at 1 year (p = 0.013). The restenosis rate of the target lesion was 13.8%; 60% were symptomatic restenosis and 40% were asymptomatic restenosis. The rate of severe stroke at 1 year after PTAS was 0%, while that in the SMT group was 9.7%.Conclusions: In a real-world Chinese cohort, PTAS for patients might be superior to SMT, and provide better long-term neurological function recovery and lower disability rate.
Long-Term Clinical and Immunological Effects of Repeated Mesenchymal Stem Cell Injections in Patients With Progressive Forms of Multiple Sclerosis
Authors: Petrou Panayiota , Kassis Ibrahim , Ginzberg Ariel , Halimi Michel , Yaghmour Nour , Abramsky Oded , Karussis Dimitrios 
Published: May 2021

Background: Mesenchymal stem cells (MSC) were shown to possess immunomodulatory and neurotrophic effects. Our previous trials, have shown that intrathecal (IT) and intravenous (IV) administration of MSCs were safe and provided indications of beneficial clinical effects.Methods: This is an open prospective study to evaluate the safety and the long-term clinical and immunological effects of multiple injections of autologous MSCs in 24 patients with active-progressive MS. At inclusion, the mean age of the patients was 47.0 ± 9.22, and the mean EDSS score was 6.75 ± 0.68 (range: 5.5–7.5). Patients were initially treated with 1 ×106 MSCS/kg of body weight (IT + IV) and subsequently with up to additional eight courses of MSCs, at intervals of 6–12 months. The duration of the trial was 4 years.Results: No serious, treatment-related adverse events were observed during the follow-up period. Twenty-two of the 24 patients were either stable or improved at the last follow-up visit. Ten patients had a lower than baseline EDSS at the last follow-up (nine were among those who received &gt;2 treatments and one in the subgroup of ≤ 2 treatments, p = 0.04). The mean EDSS score reduced from 6.75 ± 0.68 at baseline to 6.42 ± 0.84 at the last visit, during a median follow-up period of 27.8 months (p = 0.028). Immunological follow-up showed a transient upregulation of CD4+CD25+FoxP3+ cells and downregulation of the proliferative ability of lymphocytes.Conclusions: Repeated MSC treatments in patients with progressive MS were shown safe at the short/intermediate term and induced clinical benefits (especially in patients treated with &gt;2 injections) that lasted for up to 4 years, paralleled by short-term immunomodulatory effects.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04823000.
Prognostic Value of Elevated Cardiac Troponin I After Aneurysmal Subarachnoid Hemorrhage
Authors: Lin Fa , Chen Yu , He Qiheng , Zeng Chaofan , Zhang Chaoqi , Chen Xiaolin , Zhao Yuanli , Wang Shuo , Zhao Jizong 
Published: May 2021

Object: Patients with aneurysmal subarachnoid hemorrhage (aSAH) have an increased incidence of cardiac events and short-term unfavorable neurological outcomes during the acute phase of bleeding. We studied whether troponin I elevation after ictus can predict future major adverse cardiac events (MACEs) and long-term neurological outcomes after 2 years.Methods: Consecutive aSAH patients within 3 days of bleeding were eligible for review from a prospective observational cohort (ClinicalTrials.gov Identifier: NCT04785976). Potential predictors of future MACEs and unfavorable long-term neurological outcomes were calculated by Cox and logistic regression analyses. Additional Kaplan–Meier curves were performed.Results: A total of 213 patients were enrolled with an average follow-up duration of 34.3 months. Individuals were divided into two groups: elevated cTnI group and unelevated cTnI group. By the last available follow-up, 20 patients had died, with an overall all-cause mortality rate of 9.4% and an annual all-cause mortality rate of 3.8%. Patients with elevated cTnI had a significantly higher risk of future MACEs (10.6 vs. 2.1%, p = 0.024, and 95% CI: 1.256–23.875) and unfavorable neurological outcomes at discharge, 3-month, 1-, 2-years, and last follow-up (p = 0.001, p &lt; 0.001, p = 0.001, p &lt; 0.001, and p &lt; 0.001, respectively). In the Cox analysis for future MACE, elevated cTnI was the only independent predictor (HR = 5.980; 95% CI: 1.428–25.407, and p = 0.014). In the multivariable logistic analysis for unfavorable neurological outcomes, peak cTnI was significant (OR = 2.951; 95% CI: 1.376–6.323; p = 0.005). Kaplan–Meier analysis indicated that the elevated cTnI was correlated with future MACE (log-rank test, p = 0.007) and subsequent death (log-rank test, p = 0.004).Conclusion: cTnI elevation after aSAH could predict future MACEs and unfavorable neurological outcomes.
A Retrospective Study on Using a Novel Single Needle Cone Puncture Approach for the Iodine-125 Seed Brachytherapy in Treating Patients With Thoracic Malignancy
Authors: Li Fenge , Wang Liping , Zhang Yixiang , Feng Weihong , Ju Tao , Liu Zaiping , Wang Zhenglu , Du Xueming 
Published: May 2021

BackgroundPatients with progressive thoracic malignancy characterized by large irregular tumors with necrosis and life-threatening symptoms lack effective treatments. We set out to develop a single needle cone puncture method for the Iodine-125 seed (SNCP-125I) brachytherapy, and aim to report the initial results.Methods294 patients with advanced thoracic malignancy were treated with local SNCP-125I brachytherapy between March 2009 and July 2020, followed by thorough evaluation of clinical outcome, overall survival (OS), progression-free survival (PFS) and procedure-related complications after treatment.ResultsThe overall response rate (ORR) among the treated patients was 81.0% (238/294). Life-threatening symptoms due to tumor oppression, hemoptysis and large irregular tumor with necrosis were successfully alleviated after the SNCP-125I treatment with a remission rate at 91% to 94%. The median OS and PFS were 13.6 months and 5.8 months, respectively. Procedure-related side effects including pneumothorax (32/294), blood-stained sputum (8/294), subcutaneous emphysema (10/294), puncture site bleeding (16/294) and chest pain (6/294) were observed. Patients who were able to follow with chemotherapy or immunotherapy experienced extended OS and PFS, as compared with patients who opted to receive hospice care (16.5 months Vs. 11.2 months). Further pathological and immunological analysis showed that SNCP-125I induced tumor lymphocytes infiltration and long-term tumor necrosis.ConclusionSNCP-125I brachytherapy effectively eliminates life-threatening symptoms due to local tumor oppression, hemoptysis and large irregular and necrotic tumors in patients with unresectable chest malignancy and significantly induces local tumor regression. SNCP-125I brachytherapy combines with chemotherapy significantly prolong OS and PFS compare with SNCP-125I brachytherapy alone.
Molecular Characterization and Clinical Relevance of Lysine Acetylation Regulators in Urological Cancers
Authors: Zhang Jian , Zhang Chunning , Jiang Huali , Jiang Hualong , Yuan Yawei 
Published: May 2021

BackgroundLysine acetylation and deacetylation are posttranslational modifications that are able to link extracellular signals to intracellular responses. However, knowledge regarding the status of lysine regulators in urological cancers is still unknown.MethodsWe first systematically analyzed the genetic and expression alterations of 31 lysine acetylation regulators in urological cancers. The correlation between lysine acetylation regulators and activation of cancer pathways was explored. The clinical relevance of lysine acetylation regulators was further analyzed.ResultsWe identified that there are widespread genetic alterations of lysine acetylation regulators, and that their expression levels are significantly associated with the activity of cancer hallmark-related pathways. Moreover, lysine acetylation regulators were found to be potentially useful for prognostic stratification. HDAC11 may act as a potential oncogene in cell cycle and oxidative phosphorylation of urological cancers.ConclusionLysine acetylation regulators are involved in tumorigenesis and progression. Our results provide a valuable resource that will guide both mechanistic and therapeutic analyses of the role of lysine acetylation regulators in urological cancers.
SPECT/CT Imaging, Biodistribution and Radiation Dosimetry of a 177Lu-DOTA-Integrin αvβ6 Cystine Knot Peptide in a Pancreatic Cancer Xenograft Model
Authors: Sachindra Sachindra , Hellberg Teresa , Exner Samantha , Prasad Sonal , Beindorff Nicola , Rogalla Stephan , Kimura Richard , Gambhir Sanjiv Sam , Wiedenmann Bertram , Grötzinger Carsten 
Published: May 2021

IntroductionPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignant neoplasms, as many cases go undetected until they reach an advanced stage. Integrin αvβ6 is a cell surface receptor overexpressed in PDAC. Consequently, it may serve as a target for the development of probes for imaging diagnosis and radioligand therapy. Engineered cystine knottin peptides specific for integrin αvβ6 have recently been developed showing high affinity and stability. This study aimed to evaluate an integrin αvβ6-specific knottin molecular probe containing the therapeutic radionuclide 177Lu for targeting of PDAC.MethodsThe expression of integrin αvβ6 in PDAC cell lines BxPC-3 and Capan-2 was analyzed using RT-qPCR and immunofluorescence. In vitro competition and saturation radioligand binding assays were performed to calculate the binding affinity of the DOTA-coupled tracer loaded with and without lutetium to BxPC-3 and Capan-2 cell lines as well as the maximum number of binding sites in these cell lines. To evaluate tracer accumulation in the tumor and organs, SPECT/CT, biodistribution and dosimetry projections were carried out using a Capan-2 xenograft tumor mouse model.ResultsRT-qPCR and immunofluorescence results showed high expression of integrin αvβ6 in BxPC-3 and Capan-2 cells. A competition binding assay revealed high affinity of the tracer with IC50 values of 1.69 nM and 9.46 nM for BxPC-3 and Capan-2, respectively. SPECT/CT and biodistribution analysis of the conjugate 177Lu-DOTA-integrin αvβ6 knottin demonstrated accumulation in Capan-2 xenograft tumors (3.13 ± 0.63%IA/g at day 1 post injection) with kidney uptake at 19.2 ± 2.5 %IA/g, declining much more rapidly than in tumors.Conclusion177Lu-DOTA-integrin αvβ6 knottin was found to be a high-affinity tracer for PDAC tumors with considerable tumor accumulation and moderate, rapidly declining kidney uptake. These promising results warrant a preclinical treatment study to establish therapeutic efficacy.
Strategies in Rapid Genetic Diagnostics of Critically Ill Children: Experiences From a Dutch University Hospital
Authors: Imafidon Miriam E. , Sikkema-Raddatz Birgit , Abbott Kristin M. , Meems-Veldhuis Martine T. , Swertz Morris A. , van der Velde K. Joeri , Beunders Gea , Bos Dennis K. , Knoers Nine V. A. M. , Kerstjens-Frederikse Wilhelmina S. , van Diemen Cleo C. 
Published: May 2021

Background: Genetic disorders are a substantial cause of infant morbidity and mortality and are frequently suspected in neonatal intensive care units. Non-specific clinical presentation or limitations to physical examination can result in a plethora of genetic testing techniques, without clear strategies on test ordering. Here, we review our 2-years experiences of rapid genetic testing of NICU patients in order to provide such recommendations.Methods: We retrospectively included all patients admitted to the NICU who received clinical genetic consultation and genetic testing in our University hospital. We documented reasons for referral for genetic consultation, presenting phenotypes, differential diagnoses, genetic testing requested and their outcomes, as well as the consequences of each (rapid) genetic diagnostic approach. We calculated diagnostic yield and turnaround times (TATs).Results: Of 171 included infants that received genetic consultation 140 underwent genetic testing. As a result of testing as first tier, 13/14 patients received a genetic diagnosis from QF-PCR; 14/115 from SNP-array; 12/89 from NGS testing, of whom 4/46 were diagnosed with a small gene panel and 8/43 with a large OMIM-morbid based gene panel. Subsequent secondary or tertiary analysis and/or additional testing resulted in five more diagnoses. TATs ranged from 1 day (QF-PCR) to a median of 14 for NGS and SNP-array testing, with increasing TAT in particular when many consecutive tests were performed. Incidental findings were detected in 5/140 tested patients (3.6%).Conclusion: We recommend implementing a broad NGS gene panel in combination with CNV calling as the first tier of genetic testing for NICU patients given the often unspecific phenotypes of ill infants and the high yield of this large panel.
Early Resuscitation in Paediatric Sepsis Using Inotropes – A Randomised Controlled Pilot Study in the Emergency Department (RESPOND ED): Study Protocol and Analysis Plan
Authors: Harley Amanda , George Shane , King Megan , Phillips Natalie , Keijzers Gerben , Long Debbie , Gibbons Kristen , Bellomo Rinaldo , Schlapbach Luregn J. 
Published: May 2021

Introduction: Septic shock in children still carries substantial mortality and morbidity. While resuscitation with 40–60 mL/kg intravenous fluid boluses remains a cornerstone of initial resuscitation, an increasing body of evidence indicates potential for harm related to high volume fluid administration. We hypothesize that a protocol on early use of inotropes in children with septic shock is feasible and will lead to less fluid bolus use compared to standard fluid resuscitation. Here, we describe the protocol of the Early Resuscitation in Paediatric Sepsis Using Inotropes – A Randomised Controlled Pilot Study in the Emergency Department (RESPOND ED).Methods and analysis: The RESPOND ED study is an open label randomised controlled, two arm, multicentre pilot study conducted at four specialised paediatric Emergency Departments. Forty children aged between 28 days and 18 years treated for presumed septic shock will be randomized in a 1:1 ratio to early inotropes vs. standard fluid resuscitation. Early inotrope treatment is defined as the commencement of a continuous intravenous adrenaline infusion after 20 mL/kg fluid bolus resuscitation. Standard fluid resuscitation is defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to commencement of inotropes. In addition to feasibility outcomes, survival free of organ dysfunction censored at 28 days will be assessed as the main clinical outcome. The study cohort will be followed up at 28 days, and at 6 months post enrolment to assess quality of life and functional status. Biobanking nested in the study cohort will be performed to enable ancillary biomarker studies.Ethics and dissemination: The trial has ethical clearance (Children's Health Queensland, Brisbane, HREC/18/QCHQ/49168) and is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12619000828123). Enrolment commenced on July 21st, 2019. The primary manuscript will be submitted for publication in a peer-reviewed journal.Trial Registration: Australian and New Zealand Clinical Trials Registry, ACTRN12619000828123.