bluuebunny/crossref_metadata_2025_split huggingface dataset:
JAM-A Acts via C/EBP-α to Promote Claudin-5 Expression and Enhance Endothelial Barrier Function
Authors: Kakogiannos Nikolaos , Ferrari Laura , Giampietro Costanza , Scalise Anna Agata , Maderna Claudio , Ravà Micol , Taddei Andrea , Lampugnani Maria Grazia , Pisati Federica , Malinverno Matteo , Martini Emanuele , Costa Ilaria , Lupia Michela , Cavallaro Ugo , Beznoussenko Galina V. , Mironov Alexander A. , Fernandes Bethania , Rudini Noemi , Dejana Elisabetta , Giannotta Monica 
Published: July 2020

Rationale:
Intercellular tight junctions are crucial for correct regulation of the endothelial barrier. Their composition and integrity are affected in pathological contexts, such as inflammation and tumor growth. JAM-A (junctional adhesion molecule A) is a transmembrane component of tight junctions with a role in maintenance of endothelial barrier function, although how this is accomplished remains elusive.

Objective:
We aimed to understand the molecular mechanisms through which JAM-A expression regulates tight junction organization to control endothelial permeability, with potential implications under pathological conditions.

Methods and Results:
Genetic deletion of JAM-A in mice significantly increased vascular permeability. This was associated with significantly decreased expression of claudin-5 in the vasculature of various tissues, including brain and lung. We observed that C/EBP-α (CCAAT/enhancer-binding protein-α) can act as a transcription factor to trigger the expression of claudin-5 downstream of JAM-A, to thus enhance vascular barrier function. Accordingly, gain-of-function for C/EBP-α increased claudin-5 expression and decreased endothelial permeability, as measured by the passage of fluorescein isothiocyanate (FITC)-dextran through endothelial monolayers. Conversely, C/EBP-α loss-of-function showed the opposite effects of decreased claudin-5 levels and increased endothelial permeability. Mechanistically, JAM-A promoted C/EBP-α expression through suppression of β-catenin transcriptional activity, and also through activation of EPAC (exchange protein directly activated by cAMP). C/EBP-α then directly binds the promoter of claudin-5 to thereby promote its transcription. Finally, JAM-A–C/EBP-α–mediated regulation of claudin-5 was lost in blood vessels from tissue biopsies from patients with glioblastoma and ovarian cancer.

Conclusions:
We describe here a novel role for the transcription factor C/EBP-α that is positively modulated by JAM-A, a component of tight junctions that acts through EPAC to up-regulate the expression of claudin-5, to thus decrease endothelial permeability. Overall, these data unravel a regulatory molecular pathway through which tight junctions limit vascular permeability. This will help in the identification of further therapeutic targets for diseases associated with endothelial barrier dysfunction.

Graphic Abstract:

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Prevalence of Cardiovascular Comorbidities in Coronavirus Disease 2019, Severe Acute Respiratory Syndrome, and Middle East Respiratory Syndrome: Pooled Analysis of Published Data
Authors: Liu Yang , Wu Shaohui , Qin Mu , Jiang Weifeng , Liu Xu 
Published: July 2020

Background
Coronavirus disease 2019 (COVID‐19) is spreading widely around the world. We conducted this meta‐analysis to explore the prevalence of cardiovascular comorbidities in COVID‐19, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS) cases.

Methods and Results
Relevant reports updated to April 17, 2020, were searched from PubMed, Embase, Web of Science, and the Cochrane Library with no restriction on language. A random‐effects model was used in this meta‐analysis to obtain pooled proportions of cardiovascular comorbidities in COVID‐19, SARS, and MERS. A total of 22 studies (12 for COVID‐19, 4 for SARS, and 6 for MERS) were included in this analysis, and the average age of patients with COVID‐19, SARS, and MERS was 46.41±1.79, 39.16±2.25, and 52.51±4.64 years, respectively. Proportions of cardiovascular comorbidities in coronavirus diseases were as follows: COVID‐19: proportion of hypertension was 17.1% (95% CI, 13.2%–20.9%), proportion of cardiac disease was 4.5% (95% CI, 3.6%–5.5%) and proportion of diabetes mellitus was 8.5% (95% CI, 5.5%–11.4%); SARS: proportion of hypertension was 4.5% (95% CI, 2.0%–7.0%), proportion of cardiac disease was 2.1% (95% CI, 0.6%–3.7%) and proportion of diabetes mellitus was 3.7% (95% CI, 1.0%–6.4%); MERS: proportion of hypertension was 30.3% (95% CI, 18.3%–42.2%), proportion of cardiac disease was 20.9% (95% CI, 10.7%–31.1%), and proportion of diabetes mellitus was 45.4% (95% CI, 27.3%–63.5%).

Conclusions
The prevalence of cardiovascular comorbidities varies among different coronavirus‐associated diseases. With the development of time, proportions of cardiovascular comorbidities in COVID‐19 need further attention.
Comparison of Floods Driven by Tropical Cyclones and Monsoons in the Southeastern Coastal Region of China
Authors: Lu Weiwei , Lei Huimin , Yang Wencong , Yang Jingjing , Yang Dawen 
Published: July 2020

AbstractIncreasing evidence indicates that changes have occurred in heavy precipitation associated with tropical cyclone (TC) and local monsoon (non-TC) systems in the southeastern coastal region of China over recent decades. This leads to the following questions: what are the differences between TC and non-TC flooding, and how do TC and non-TC flooding events change over time? We applied an identification procedure for TC and non-TC floods by linking flooding to rainfall. This method identified TC and non-TC rainfall–flood events by the TC rainfall ratio (percentage of TC rainfall to total rainfall for rainfall–flood events). Our results indicated that 1) the TC rainfall–flood events presented a faster runoff generation process associated with larger flood peaks and rainfall intensities but smaller rainfall volumes, compared to that of non-TC rainfall–flood events, and 2) the magnitude of TC floods exhibited a decreasing trend, similar to the trend in the amount and frequency of TC extreme precipitation. However, the frequency of TC floods did not present obvious changes. In addition, non-TC floods decreased in magnitude and frequency while non-TC extreme precipitation showed an increase. Our results identified significantly different characteristics between TC and non-TC flood events, thus emphasizing the importance of considering different mechanisms of floods to explore the physical drivers of runoff response. Also, our results indicated that significant decreases occurred in the magnitude, but not the frequency, of floods induced by TC from the western North Pacific, which is the most active ocean basin for TC activity, and thus can provide useful information for future studies on the global pattern of TC-induced flooding.
Understanding Health Care Utilization and Mortality After Emergency General Surgery in Patients With Underlying Liver Disease
Authors: Tennakoon Lakshika , Baiu Ioana , Concepcion Waldo , Melcher Marc L. , Spain David A. , Knowlton Lisa M. 
Published: July 2020

Background Mortality and complications are not well defined nationally for emergency general surgery (EGS) patients presenting with underlying all-cause liver disease (LD). Study design We analyzed the 2012-2014 National Inpatient Sample for adults (aged ≥ 18 years) with a primary EGS diagnosis. Underlying LD included International Classification of Diseases, Ninth Revision, Clinical Modification codes for alcoholic and viral hepatitis, malignancy, congenital etiologies, and cirrhosis. The primary outcome was mortality; secondary outcomes included complications, operative intervention, and costs. Results Of the 6.8 million EGS patients, 358 766 (5.3%) had underlying LD. 59.1% had cirrhosis, 6.7% had portal hypertension, and 13.7% had ascites. Compared with other EGS patients, EGS-LD patients had higher mean costs ($12 847 vs $10 234, P < .001). EGS-LD patients were less likely to have surgery (26.1% vs 37.0%, P < .001) but for those who did, mortality was higher (4.8% vs 1.8%, P < .001). Risk factors for mortality included ascites (adjusted odds ratio [aOR] = 2.68, P < .001), dialysis (aOR = 3.44, P < .001), sepsis (aOR = 8.97, P < .001), and respiratory failure requiring intubation (aOR = 10.40, P < .001). Odds of death increased in both surgical (aOR = 4.93, P < .001) and non-surgical EGS-LD patients (aOR = 2.56, P < .001). Conclusions Underlying all-cause LD among EGS patients is associated with increased in-hospital mortality, even in the absence of surgical intervention.
Assessment of Unused Opioids Following Ambulatory Surgery
Authors: Dixit Anjali A. , Chen Catherine L. , Inglis-Arkell Christina , Manuel Solmaz P. 
Published: July 2020

Background Surgery is a risk factor for opioid initiation and subsequent abuse. Discharge opioid prescription patterns after surgery are often varied and not evidence based, which may lead to unnecessary prescription of opioids. We aimed to assess opioid prescribing and unused opioid prescriptions in ambulatory surgery patients at our academic hospital. Methods We conducted a retrospective observational study based on phone survey and electronic medical records. Adult patients who underwent ambulatory surgery at our large, multisite, tertiary-care hospital system were asked whether they were using the opioids that were prescribed at discharge. Our main outcomes were opioid prescription (defined as being prescribed an opioid on discharge) and unused opioid prescription (defined as being prescribed an opioid but not taking any opioids on postoperative day 1). We evaluated predictors of opioid prescription and unused opioid prescription through univariable and multivariable analyses. We also stratified outcomes by surgical service. Results Of 4248 adult patients who underwent ambulatory surgical procedures, 3279 (77.2%) responded to the survey. Of all responders, 2146 (65.4%) were prescribed postoperative opioids, and 1240 (57.8%) reported not taking them on postoperative day 1. The highest rates of unused opioid prescriptions were for patients whose primary service were orthopedic surgery (65%) and plastic surgery (62%). Discussion Opioid prescribing and unused opioid prescriptions are prevalent in our hospital’s ambulatory surgical population. Patients undergoing selected ambulatory surgical procedures may not require as much opioid as is currently being prescribed.
Unmet Emotional Support Needs Among Diverse Patients with Colorectal Cancer
Authors: Kapadia Muneera R. , Veenstra Christine M. , Davis Rachel E. , Hawley Sarah T. , Morris Arden M. 
Published: July 2020

Background Social support, which is partly emotional support, is associated with adherence to colorectal cancer (CRC) treatment, quality of life, and survival. We hypothesized that the needs, sources, and availability of emotional support would vary by race and income among CRC patients and sought to quantify the emotional support and the perceived adequacy of support reported by patients. Methods We surveyed CRC patients from Detroit and Georgia Surveillance, Epidemiology and End Results registries about the quantity and quality of emotional support received from different sources. We tested differences using the chi-square test, t-tests, and logistic regression. Results There were 1909 patients who met inclusion criteria and 1301 (68%) completed surveys. Among respondents, 68% were white, 25% black, and 7% other. Black patients were more likely to be female and younger and reported lower annual income and education. Patients reported high support from several sources. Among those with a spouse/partner (58%), 95% reported high levels of support; however, older, black, female, or lower income patients were less likely to have spouses/partners ( P < .001). Patients also endorsed high support from family (88.6%), important others (82.9%), and clinicians (71.3%). Black patients were less likely than white patients to report support that was “just right” ( P < .001). Discussion Most patients reported high emotional support from at least 1 source. Black patients were most at risk for low support or unmet support needs. Spouse/partner support was important but only available to 58% of respondents. Patients at risk for unmet emotional support needs may benefit from additional support resources.
Emergency Management of Blunt Splenic Injury in Hypotensive Patients
Authors: Guinto Robyn , Greenberg Patricia , Ahmed Nasim 
Published: July 2020

Objectives The purpose of this study is to examine the outcomes of splenic angioembolization (SAE) as the first modality for nonoperative management (NOM) in hypotensive patients with high-grade splenic injuries. Methods Data were collected from the 2007-2010 National Trauma Data Bank data sets of the United States. The data included patients with massive blunt splenic injuries with an Abbreviated Injury Scale (AIS) of 4 or 5, initial systolic blood pressure ≤90, and who underwent either a total splenectomy or SAE (Group 1 and Group 2, respectively) within 4 hours of hospital arrival. The outcomes of interest are in-hospital mortality and complications. Results Of the 1052 patients analyzed, 996 (94.7%) underwent total splenectomy while 56 (5.3%) underwent SAE. There were significant differences regarding injury mechanism ( P = .01) and the proportion of patients with an AIS of 5 (57.6% vs 39.3% respectively, P = .01). A significantly higher number of patients, however, developed organ space infections (3.9% vs 11.6%, P = .02) in Group 2. The multivariate logistic regression model for mortality, which accounted for demography, Glasgow Coma Scale Motor (GCSM) score, Injury Severity Score (ISS), AIS, time to procedure, and procedure type showed the procedure type was not a contributing factor to patient mortality, but higher age, ISS, and lower GCSM score were strong predictors of mortality. Conclusion The treatment of approximately 95% of hypotensive patients with massive splenic injury was total splenectomy. However, if the interventional radiology resources are immediately available, SAE can be used as a first intervention without an increased risk of mortality.
Predictors of employment in people with moderate to severe mental illness participating in a randomized controlled trial of Individual Placement and Support (IPS)
Authors: Fyhn Tonje , Øverland Simon , Reme Silje E 
Published: July 2020

Background: Many people with moderate to severe mental illness have a desire to obtain ordinary employment. To aid further development of health and social services for this group, the aim of this study was to examine candidate modifiable and prognostic markers of employment, and moderating effects of group allocation in a clinical trial. Method: The sample consists of 327 patients in treatment for mental illness, randomized to Individual Placement and Support (IPS) or treatment as usual (TAU) as part of a clinical trial. Psychosocial and demographic baseline characteristics were included as predictors in log binary regression analyses with employment 18 months after inclusion as the outcome, and group allocation as the moderator (IPS or TAU). Results: Directive emotional support and non-directive instrumental support seemed to positively predict employment, but effects were small. Involuntary hospitalization seemed to be a strong negative predictor of employment. Group allocation did not moderate any main effects. Conclusion: Interpretation of the findings suggest that attention should be given to certain aspects of health and social services provided to this target group, and in particular the effect of receiving appropriate types of social support. The findings are novel because social support and involuntary hospitalization do not seem to have been included in previous predictor studies. The results from this study identify new topics for research on employment outcomes for this population.
Severe aortic valve regurgitation requiring mechanical aortic valve replacement following Impella device implantation
Authors: Vila Pierre , de Vere Felicity , Simon André , Walker Christopher 
Published: July 2020

Introduction: We describe a patient who developed severe aortic regurgitation following Impella left ventricular assist device implantation requiring aortic valve replacement. Case report: A previously healthy 34-year-old female presented with chest pain and flu-like symptoms. Electrocardiogram showed widespread ST elevation and serum troponin was raised, consistent with myocarditis. Coronary angiography was normal but the right coronary artery dissected. Subsequent cardiogenic shock required veno-arterial extracorporeal membrane oxygenation and Impella implantation. Myocardial function recovered, but upon removal of the Impella, severe aortic regurgitation was present and she underwent aortic valve replacement, making a full recovery. Discussion: Aortic regurgitation is a rare complication of Impella implantation, and to our knowledge, this is the first reported case successfully treated with aortic valve replacement. Veno-arterial extracorporeal membrane oxygenation and Impella used in tandem are relatively novel, and may add synergistic benefit to strategies for acute cardiogenic shock. Conclusion: Echocardiography must include frequent assessment of both valvular and myocardial function after Impella removal.
Accessory extensor pollicis longus tendon in emergency surgery
Authors: Jiang Qing , Zhou Haiying , Huang Kai , Lu Hui 
Published: July 2020

Background A true accessory extensor tendon of the thumb seems to be rare. We found a variation of the accessory extensor pollicis longus (EPL) tendon while performing an emergency surgical procedure. Identification of this accessory tendon during emergency surgery has not been previously reported. Case presentation: A 43-year-old man presented to our hospital after sustaining a work-related injury involving a saw. During the operation, the tendons of the EPL, accessory EPL, and extensor pollicis brevis were severed. The lacerated tendon and tendon sheath were repaired, and the wrist and thumb were positioned in extension. The patient’s postoperative activity returned to normal without the need for a second tendon release operation. Conclusions Surgeons should be aware of this anatomic anomaly of the EPL tendon. Presentation of our case increases clinicians’ chances of preoperatively detecting this anomaly, which can improve surgical outcomes.
Prospective Long-term Follow-up of Autologous Chondrocyte Implantation With Periosteum Versus Matrix-Associated Autologous Chondrocyte Implantation: A Randomized Clinical Trial
Authors: Barié Alexander , Kruck Patrizia , Sorbi Reza , Rehnitz Christoph , Oberle Doris , Walker Tilman , Zeifang Felix , Moradi Babak 
Published: July 2020

Background: Matrix-associated autologous chondrocyte implantation (MACI) is a further development of the original autologous chondrocyte implantation periosteal flap technique (ACI-P) for the treatment of articular cartilage defects. Purpose: We aimed to establish whether MACI or ACI-P provides superior long-term outcomes in terms of patient satisfaction, clinical assessment, and magnetic resonance imaging (MRI) evaluation. Study Design: Randomized controlled trial; Level of evidence, 2. Methods: A total of 21 patients with cartilage defects at the femoral condyle were randomized to MACI (n = 11) or ACI-P (n = 10) between the years 2004 and 2006. Patients were assessed for subjective International Knee Documentation Committee (IKDC) score, Lysholm and Gillquist score, Tegner Activity Score, and 36-Item Short Form Health Survey (SF-36) preoperatively (T0), at 1 and 2 years postoperatively (T1, T2), and at the final follow-up 8 to 11 years after surgery (T3). Onset of osteoarthritis was determined using the Kellgren-Lawrence score and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and delayed gadolinium-enhanced MRI of cartilage was used to evaluate the cartilage. Adverse events were recorded to assess safety. Results: There were 16 patients (MACI, n = 9; ACI-P, n = 7) who were reassessed on average 9.6 years after surgery (76% follow-up rate). The Lysholm and Gillquist score improved in both groups after surgery and remained elevated but reached statistical significance only in ACI-P at T1 and T2. IKDC scores increased significantly at all postoperative evaluation time points in ACI-P. In MACI, IKDC scores showed a significant increase at T1 and T3 when compared with T0. In the majority of the patients (10/16; MACI, 5/9; ACI-P, 5/7) a complete defect filling was present at the final follow-up as shown by the MOCART score, and 1 patient in the ACI-P group displayed hypertrophy of the repair tissue, which represents 6% of the whole study group and 14.3% of the ACI-P group. Besides higher SF-36 vitality scores in ACI-P at T3, no significant differences were seen in clinical scores and MRI scores between the 2 methods at any time point. Revision rate was 33.3% in MACI and 28.6% in ACI-P at the last follow-up. Conclusion: Our long-term results suggest that first- and third-generation ACI methods are equally effective treatments for isolated full-thickness cartilage defects of the knee. With the number of participants available, no significant difference was noted between MACI and ACI-P at any time point. Interpretation of our data has to be performed with caution due to the small sample size, which was further limited by a loss to follow-up of 24%.
Anterior Cruciate Ligament Reconstructions With Quadriceps Tendon Autograft Result in Lower Graft Rupture Rates but Similar Patient-Reported Outcomes as Compared With Hamstring Tendon Autograft: A Comparison of 875 Patients
Authors: Runer Armin , Csapo Robert , Hepperger Caroline , Herbort Mirco , Hoser Christian , Fink Christian 
Published: July 2020

Background: Graft rupture is a devastating outcome after anterior cruciate ligament (ACL) reconstruction (ACLR). Little is known about graft rupture rates as well as clinical and functional outcomes after ACLR with quadriceps tendon (QT) autografts. Purpose: To compare QT with hamstring tendon (HT) autografts in terms of the rates of graft and contralateral ACL rupture as well as patient-reported outcome measures. Study Design: Cohort study; Level of evidence, 3. Methods: All primary ACLRs performed between 2010 and 2016 were followed prospectively for 24 months through the recording of graft ruptures and contralateral ACL injuries as well as patient-administered questionnaires. Results: A total of 875 patients were included in the study. Three factors—graft type, age group, and activity level—had a significant value in predicting the need for revision surgery. The odds of revision surgery were 5.5 times greater in children younger than 15 years than in adults older than 45 years, 3.6 times greater in patients with high activity levels than low activity levels, and 2.7 times greater in patients receiving an HT autograft as compared with a QT autograft. A significantly higher rate of ipsilateral graft ruptures versus contralateral ACL injuries was observed in the HT group (4.9% vs 2.3%; odds ratio, 2.1; P = .01) but not in the QT group (2.8% vs 2.3%). The difference in the ratios of graft and contralateral ACL ruptures was even more pronounced in highly active patients treated with HT autografts (11.1% vs 4.2%; odds ratio, 2.6; P = .01) as compared with QT autografts (5.0% vs 2.8%; P = .48). Two-year measures of Lysholm scores (mean ± SD: QT, 86.0 ± 22.3; HT, 89.4 ± 16.4) and Tegner activity scores (QT, 6.1 ± 2.0; HT, 5.7 ± 1.9) as well as visual analog scale pain (QT, 0.8 ± 1.3; HT, 0.7 ± 1.1) did not differ between grafts. Conclusion: Graft choice does not influence clinical and functional outcomes 2 years after ACLR. However, 3 factors—graft type, age group, and activity level—have a significant value in predicting the need for revision surgery. Patients treated with HT autografts have a significantly higher, activity-dependent risk of revision surgery and experience more ipsilateral graft ruptures than subsequent contralateral ACL injuries when compared with patients treated with QT autografts. Young age and high activity level are significant predictors for ACL revision surgery.