bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Kidney Injury in Traumatic Brain Injury Patients: Results From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury Study
Authors: Robba Chiara , Banzato Erika , Rebora Paola , Iaquaniello Carolina , Huang Chao-Yuan , Wiegers Eveline J. A. , Meyfroidt Geert , Citerio Giuseppe 
Published: October 2020

OBJECTIVES:
Acute kidney injury is frequent in polytrauma patients, and it is associated with increased mortality and extended hospital length of stay. However, the specific prevalence of acute kidney injury after traumatic brain injury is less recognized. The present study aims to describe the occurrence rate, risk factors, timing, and association with outcome of acute kidney injury in a large cohort of traumatic brain injury patients.

DESIGN:
The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury is a multicenter, prospective observational, longitudinal, cohort study.

SETTING:
Sixty-five ICUs across Europe.

PATIENTS:
For the present study, we selected 4,509 traumatic brain injury patients with an ICU length of stay greater than 72 hours and with at least two serum creatinine values during the first 7 days of ICU stay.

MEASUREMENTS AND MAIN RESULTS:
We classified acute kidney injury in three stages according to the Kidney Disease Improving Global Outcome criteria: acute kidney injury stage 1 equals to serum creatinine × 1.5–1.9 times from baseline or an increase greater than or equal to 0.3 mg/dL in 48 hours; acute kidney injury stage 2 equals to serum creatinine × 2–2.9 times baseline; acute kidney injury stage 3 equals to serum creatinine × three times baseline or greater than or equal to 4 mg/dL or need for renal replacement therapy. Standard reporting techniques were used to report incidences. A multivariable Cox regression analysis was performed to model the cause-specific hazard of acute kidney injury and its association with the long-term outcome. We included a total of 1,262 patients. The occurrence rate of acute kidney injury during the first week was as follows: acute kidney injury stage 1 equals to 8% (n = 100), acute kidney injury stage 2 equals to 1% (n = 14), and acute kidney injury stage 3 equals to 3% (n = 36). Acute kidney injury occurred early after ICU admission, with a median of 2 days (interquartile range 1–4 d). Renal history (hazard ratio = 2.48; 95% CI, 1.39–4.43; p = 0.002), insulin-dependent diabetes (hazard ratio = 2.52; 95% CI, 1.22–5.197; p = 0.012), hypernatremia (hazard ratio = 1.88; 95% CI, 1.31–2.71; p = 0.001), and osmotic therapy administration (hazard ratio = 2.08; 95% CI, 1.45–2.99; p < 0.001) were significantly associated with the risk of developing acute kidney injury. Acute kidney injury was also associated with an increased ICU length of stay and with a higher probability of 6 months unfavorable Extended Glasgow Outcome Scale and mortality.

CONCLUSIONS:
Acute kidney injury after traumatic brain injury is an early phenomenon, affecting about one in 10 patients. Its occurrence negatively impacts mortality and neurologic outcome at 6 months. Osmotic therapy use during ICU stay could be a modifiable risk factor.
Clinical management of cerebral small vessel disease: a call for a holistic approach
Authors: Clancy Una , Appleton Jason P. , Arteaga Carmen , Doubal Fergus N. , Bath Philip M. , Wardlaw Joanna M. 
Published: October 2020

Abstract
Cerebral small vessel disease (SVD) is a common global brain disease that causes cognitive impairment, ischemic or hemorrhagic stroke, problems with mobility, and neuropsychiatric symptoms. The brain damage, seen as focal white and deep grey matter lesions on brain magnetic resonance imaging (MRI) or computed tomography (CT), typically accumulates “covertly” and may reach an advanced state before being detected incidentally on brain scanning or causing symptoms. Patients have typically presented to different clinical services or been recruited into research focused on one clinical manifestation, perhaps explaining a lack of awareness, until recently, of the full range and complexity of SVD.
In this review, we discuss the varied clinical presentations, established and emerging risk factors, relationship to SVD features on MRI or CT, and the current state of knowledge on the effectiveness of a wide range of pharmacological and lifestyle interventions. The core message is that effective assessment and clinical management of patients with SVD, as well as future advances in diagnosis, care, and treatment, will require a more “joined-up”’ approach. This approach should integrate clinical expertise in stroke neurology, cognitive, and physical dysfunctions. It requires more clinical trials in order to improve pharmacological interventions, lifestyle and dietary modifications. A deeper understanding of the pathophysiology of SVD is required to steer the identification of novel interventions. An essential prerequisite to accelerating clinical trials is to improve the consistency, and standardization of clinical, cognitive and neuroimaging endpoints.
Continuous Aerobic Exercise Prevents Detrimental Remodeling and Right Heart Myocyte Contraction and Calcium Cycling Dysfunction in Pulmonary Artery Hypertension
Authors: Silva Franciany de Jesus , Drummond Filipe Rios , Fidelis Meilene Ribeiro , Freitas Maíra Oliveira , Leal Tiago Ferreira , de Rezende Leonardo Mateus Teixeira , de Moura Anselmo Gomes , Carlo Reis Emily Correna , Natali Antônio José 
Published: October 2020

Abstract:
Pulmonary artery hypertension (PAH) imposes right heart and lung detrimental remodeling which impairs cardiac contractility, physical effort tolerance, and survival. The effects of an early moderate-intensity continuous aerobic exercise training on the right ventricle and lung structure, and on contractility and the calcium (Ca2+) transient in isolated myocytes from rats with severe PAH induced by monocrotaline were analyzed. Rats were divided into control sedentary (CS), control exercise (CE), monocrotaline sedentary (MS), and monocrotaline exercise (ME) groups. Animals from control exercise and ME groups underwent a moderate-intensity aerobic exercise on a treadmill (60 min/d; 60% intensity) for 32 days, after a monocrotaline (60 mg/kg body weight i.p.) or saline injection. The pulmonary artery resistance was higher in MS than in control sedentary (1.36-fold) and was reduced by 39.39% in ME compared with MS. Compared with MS, the ME group presented reduced alveolus (17%) and blood vessel (46%) wall, fibrosis (25.37%) and type I collagen content (55.78%), and increased alveolus (52.96%) and blood vessel (146.97%) lumen. In the right ventricle, the ME group exhibited diminished hypertrophy index (25.53%) and type I collagen content (40.42%) and improved myocyte contraction [ie, reduced times to peak (29.27%) and to 50% relax (13.79%)] and intracellular Ca2+ transient [ie, decreased times to peak (16.06%) and to 50% decay (7.41%)] compared with MS. Thus, early moderate-intensity continuous aerobic exercise prevents detrimental remodeling in the right heart and lung increases in the pulmonary artery resistance and dysfunction in single myocyte contraction and Ca2+ cycling in this model.
Ocular Surface and Conjunctival Cytology Findings in Patients With Confirmed COVID-19
Authors: Bozkurt Erdinç , Özateş Serdar , Muhafız Ersin , Yılmaz Fatma , Calıskan Okan 
Published: October 2020

Purpose:
To assess the effect of severe acute respiratory syndrome coronavirus-2 infection on the conjunctiva and tear film.

Methods:
Thirty-eight patients with confirmed COVID-19 and 31 healthy controls were included in this prospective and observational study. Individuals with COVID-19 formed the patient group, and healthy individuals formed the control group. Conjunctival impression cytology (CIC), TBUT, Schirmer II test, and ocular surface disease index were evaluated in all participants.

Results:
No significant difference was observed regarding the mean age and gender between the groups (P=0.786 and P=0.122, respectively). The mean TBUT and Schirmer II test results did not differ between the two groups (P=0.496 and P=0.447, respectively). The CIC results revealed decreased density and cell size of goblet cells and moderate to high enlargement, squamous changes, and increased nucleocytoplasmic ratio in nongoblet epithelial cells in the COVID-19 group compared with the control group. Based on the Nelson classification in CIC samples, 60.6% of the COVID-19 group and 19.4% of the control group had changes consistent with grade 2 or above. The presence of neutrophils in CIC was significantly higher in the COVID-19 group (P<0.001), whereas the presence of lymphocyte was similar between the two groups (P=0.247).

Conclusion:
This study revealed the pathological conjunctival alterations in patients with COVID-19 and demonstrated that pathological ocular surface alterations may present even at the beginning of COVID-19 without clinically significant ocular manifestation.
Ocular Outcome of Brazilian Patients With Congenital Toxoplasmosis
Authors: Lago Eleonor Gastal , Endres Mariana Miranda , Scheeren Marôla Flores da Cunha , Fiori Humberto Holmer 
Published: October 2020

Background:
Retinochoroiditis is the most frequent manifestation of congenital toxoplasmosis. We aimed to describe the ocular outcome and factors that may influence the visual prognosis of these patients.

Methods:
Cohort of patients with confirmed congenital toxoplasmosis seen between 1996 and 2017 in Porto Alegre, southern Brazil.

Results:
Seventy-seven patients were included, of which 65 (85.5%) were identified by routine screening. Median age at the end of the follow-up was 10 years (minimum 2, maximum 25). Retinochoroiditis was present in 55 patients (71.4%). New retinochoroidal lesions developed after the first year of life in 77.8% of the patients who began treatment after the fourth month of life, compared with 35.2% among those treated before 4 months of life (relative risk = 0.45, 95% confidence intervals: 0.27–0.75, P = 0.02) and 33.3% among those treated before 2 months of life (relative risk = 0.42, 95% confidence intervals: 0.25–0.72, P = 0.01). There was a peak incidence of new retinochoroidal lesions between 4 and 5 years and another peak between 9 and 14 years, the latter only among girls. Thirty-four patients with retinochoroiditis were followed up for 10 years or more, and the school performance was appropriate in 28 (82.4%).

Conclusions:
The high incidence of new retinochoroidal lesions during the follow-up period indicates the importance of long-term follow-up of patients with congenital toxoplasmosis. Initiating treatment within the first 4 months of life, especially within the first 2 months, was a protective factor against the later development of retinochoroiditis. Despite the usual favorable prognosis, the high morbidity of congenital toxoplasmosis in Brazil was confirmed.
Physician prediction of 1-year mortality in the cardiac catheterization laboratory: comparison to a validated risk score
Authors: Sarathy Kiran , Jung Richard G. , Simard Trevor , Parlow Simon , Di Santo Pietro , Moreland Robert , Jung Young , Abdel-Razek Omar , Boland Paul , Russo Juan J , Chong Aun-Yeong , So Derek , Froeschl Michael , Dick Alexander , Glover Christopher , Labinaz Marino , Le May Michel , Hibbert Benjamin 
Published: October 2020

Background
Physician perception of procedural risk and clinical outcome can affect revascularization decision making. Public reporting of percutaneous coronary intervention outcomes accentuates the need for accuracy in risk prediction in order to avoid a treatment paradox of undertreating the highest risk patients. Our study compares a validated risk score to physician prediction (PP) of 1-year mortality based on clinical impression at the time of invasive angiography.

Methods and results
We performed a cohort study between August 2015 and May 2018 to determine the discriminative accuracy of interventional cardiologists on one-year mortality of the treated patient. PP of one-year mortality was compared to the New York State Percutaneous Coronary Intervention Reporting System (NYPCIRS) score in predicting mortality. Three thousand seven hundred ninety-two patients were followed with a median follow-up period of 14.4 months (interquartile range 12.4–18.1 months) and 165 patients (4.4%) died within one-year. PP of mortality was associated with one-year mortality with a hazard ratio of 8.78 (95% confidence interval 5.24–14.71, P < 0.0001). Clinical presentation in the form of cardiogenic shock, return of spontaneous circulation, and liver and renal dysfunction were associated with PP. Diagnostic accuracy and specificity were improved in PP compared to NYPCIRS. The combination of PP to NYPCIRS improved the overall c-statistic and diagnostic yield.

Conclusion
PP appears to be especially specific and accurate for prediction of mortality compared to NYPCIRS though it lacks sensitivity. Furthermore, the combination of PP with NYPCIRS improved the c-statistic and diagnostic yield. Overall, the utility of PP with an objective risk score improves the diagnostic accuracy of mortality prediction.
Pre-infarction angina is associated with improved prognosis in diabetic patients with ST-elevation myocardial infarction – data from a contemporary cohort
Authors: Fontes Oliveira Marta , Costa Ricardo , Frias André , Santos Raquel , Brochado Bruno , Santos Mário , Silveira João , Cabral Sofia , Luz André , Torres Severo 
Published: October 2020

Background
Pre-infarction angina (PIA) is associated with improved prognosis in patients with ST-elevation myocardial infarction (STEMI). Some studies suggest that diabetes may blunt the effect of ischaemic preconditioning. We sought to study the impact of PIA in diabetic patients with STEMI.

Methods
Consecutive patients with STEMI who underwent primary angioplasty were included. PIA was defined as ≥1 episode of chest pain during the week preceding STEMI diagnosis. Incident major adverse cardiovascular events (MACE) were defined as the first occurrence of all-cause death, stroke or acute myocardial infarction.

Results
Of the 1143 included patients, 25% were diabetic and 32% had a history of PIA. Diabetic patients with PIA had smaller infarct sizes as estimated by peak creatine kinase (CK) [1144 (500–2212) vs. 1715 (908–3309) U/L, P = 0.003] and peak troponin [3.30 (1.90–6.58) vs. 4.88 (2.50–9.58) ng/ml, P = 0.002], compared to diabetics without PIA. They also had a lower likelihood of evolving with moderate to severe reduced left ventricle ejection fraction (LVEF) (25.6%, n = 22 vs. 46.6%, n = 82, P = 0.001). In non-diabetic patients, PIA was associated with reduced peak CK [1549 (909–2909) vs. 1793 (996–3078), P = 0.0497], but not troponin (3.74 [2.23–7.11] vs. 4.56 [2.44–7.77] ng/ml, P = 0.19), and was not associated with reduced LVEF (32.0%, n = 85 vs. 37.4%, n = 207, P = 0.13). Both diabetic and non-diabetic patients with PIA had a lower likelihood of evolving with a Killip class III/VI (non-diabetic patients: 5.6% vs. 14.1%, P = 0.002; diabetic patients: 12.8% vs. 24.6%, P = 0.049). Over a median follow-up of 18.0 (12.1–25.5) months, PIA was associated with a significant reduction in the incidence of MACE [hazard ratio 0.52, 95% confidence interval (CI) 0.37–0.74, P < 0.001], irrespective of diabetes status.

Conclusion
PIA is an independent predictor of favourable outcomes in the setting of STEMI for both diabetic and non-diabetic patients.
Delirium is an important predictor of mortality in elderly patients with ST-elevation myocardial infarction: insight from National Inpatient Sample database
Authors: Patil Shivaraj , Gonuguntala Karthik , Rojulpote Chaitanya , Kumar Manish , Corradi John P. , Chen Kai 
Published: October 2020

Objective
Delirium is a frequently encountered clinical condition in hospitalized patients and is known to be associated with poor outcomes. This study aims to assess the impacts of delirium in elderly patients undergoing percutaneous coronary intervention (PCI) following ST-elevation myocardial infarction (STEMI).

Methods
We queried the National Inpatient Samples from 2010 to 2014 to identify all patients aged 65 and older, and admitted with a primary diagnosis of STEMI undergoing PCI by using the International Classification of Diseases-Ninth Edition-Clinical Modification diagnosis codes. The patients with delirium from this cohort were further evaluated. Multivariate regression model with SPSS Statistics 25.0 (IBM Corp., Armonk, New York, USA) was used to study the association between delirium and clinical outcomes including in-hospital mortality and length of stay (LOS).

Results
Out of weighted 42 980 patients aged ≥65 years with STEMI and PCI, delirium was present in 774 patients, accounting for 1.8% of this cohort. These patients were found to be older and had more underlying co-morbidities, compared to those without delirium [Median Charlson score 2 (1; 3) vs. 0 (0; 2); P < 0.001]. In-hospital mortality in STEMI patients with delirium was significantly higher than those without delirium [42.7% vs. 7.6%; unadjusted odds ratio (OR) 9.07; 95% confidence interval (CI) 6.55–12.57; P < 0.001; adjusted OR 1.86; 95% CI 1.13–3.04; P = 0.014].

Conclusion
Older age and comorbidities are known predisposing factors for delirium, which is in turn associated with higher in-hospital mortality and increased LOS in elderly patients with STEMI who undergo PCI. This study underscores the role of delirium and implicates the importance of further studies in recognition and targeted care of delirium.
Essential amino acid formulations to prevent mitochondrial dysfunction and oxidative stress
Authors: Ruocco Chiara , Segala Agnese , Valerio Alessandra , Nisoli Enzo 
Published: October 2020

Purpose of review
Both restriction and supplementation of specific amino acids or branched-chain amino acids (BCAAs) are described to improve metabolic homeostasis, energy balance, and health span. This review will discuss the recent findings of the role of amino acid supplements in the regulation of mitochondrial health.

Recent findings
A mixture of essential amino acids (EAAs), BCAA enriched mixture, was found to extend healthy life span in elderly mice and prevent multiple diseases associated with an energy deficit, similarly to caloric restriction or fasting-mimicking diets. A growing body of evidence highlights mitochondria as the central target of this supplement: it promotes mitochondrial biogenesis and the activation of antioxidant defence systems in different physiological (e.g., exercise or ageing) or pathological conditions (e.g., sarcopenia, muscular dystrophy, liver steatosis, or impaired cognition). Based on these results, new formulas have been created enriched with Krebs cycle substrates, behaving more efficiently than BCAA enriched mixture.

Summary
EAA-BCAA balanced supplements might be valuable not only for healthy individuals undergoing to energy deficit (e.g., athletes) during strenuous exercise or training but also against diseases characterized by a dysregulated catabolic state or mitochondrial dysfunction, such as age-related disorders. The associated mechanistic processes should be identified as potential pharmacological targets.
Inherited disorders of sulfur amino acid metabolism: recent advances in therapy
Authors: Kožich Viktor , Majtan Tomas 
Published: October 2020

Purpose of review
Metabolism of sulfur amino acids (SAA) provides compounds important for many cellular functions. Inherited disorders of SAA metabolism are typically severe multisystemic diseases affecting brain, liver, connective tissue, or vasculature. The review summarizes the present therapeutic approaches and advances in identifying novel treatment targets, and provides an overview of new therapies.

Recent findings
Current treatments of genetic disorders of SAA metabolism are primarily based on modulation of affected pathways by dietary measures and provision of lacking products or scavenging of toxic molecules. Recent studies identified additional therapeutic targets distant from the primary defects and explored ideas envisioning novel treatments, such as chaperone and gene therapy. Recombinant protein production and engineering resulted in development and clinical testing of enzyme therapies for cystathionine β-synthase deficiency, the most common inborn error of SAA metabolism.

Summary
Complex regulation of pathways involved in SAA metabolism and cellular consequences of genetic defects in SAA metabolism are only partially understood. There is a pressing need to increase substantially our knowledge of the disease mechanisms to develop more effective therapies for patients suffering from these rare disorders.
Protein and amino acids in nonalcoholic fatty liver disease
Authors: Tricò Domenico , Biancalana Edoardo , Solini Anna 
Published: October 2020

Purpose of review
In this review, the latest evidence on the influence of dietary protein and plasma amino acids in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) is discussed.

Recent findings
Increasing protein consumption during weight loss and maintenance may help reduce liver fat content. Conversely, high protein intake characteristic of the unhealthy Western diet is associated with increased NAFLD prevalence and severity. Plasma concentration of several amino acids, including branched-chain (BCAA) and aromatic amino acids (AAA), is altered in NAFLD. Excess amino acid availability contributes to intrahepatic fat accumulation and may reflect poor dietary habits and dysregulation of amino acid metabolic processing in both liver and peripheral tissues. Specific amino acid patterns, characterized by increased BCAA, AAA, alanine, glutamate, lysine levels, and decreased glycine and serine levels, may be used for early detection of NAFLD and noninvasive assessment of its histological severity.

Summary
Mechanistic studies in NAFLD have been mostly focused on carbohydrate and fat metabolism, while little is known about the influence of protein and amino acids. Moreover, intervention and observational studies on the relation between protein intake and NAFLD yielded conflicting results. Filling the current knowledge gaps would help define the optimal diet composition for NAFLD prevention and management. Furthermore, metabolomics studies may provide insight into the pathogenesis of NAFLD, identify useful diagnostic and prognostic biomarkers, and unravel novel pharmacological targets and treatment options.
Pepsin in gastroesophageal and extraesophageal reflux: molecular pathophysiology and diagnostic utility
Authors: Samuels Tina L. , Johnston Nikki 
Published: October 2020

Purpose of review
Gastroesophageal and extraesophageal reflux are prevalent and costly diseases. Recognition of the pathogenicity of nonacid reflux has stimulated interest in alternatives to acid-targeting diagnostics and therapeutics. Pepsin is the most deleterious enzyme in refluxate, eliciting inflammatory and carcinogenic effects irrespective of acid. Its presence in all refluxate and detection in saliva have situated pepsin as the most widely researched biomarker for reflux today. This review summarizes emerging findings regarding pepsin-mediated damage during reflux and developments in pepsin-targeting diagnostics.

Recent findings
New evidence supports a role for pepsin in epithelial--mesenchymal transition, an important process in carcinogenesis and fibrosis. The first global transcriptomic analysis of pepsin-exposed laryngeal cells was described, yielding evidence of a putative airway pepsin receptor. Evaluation of pepsin diagnostics highlighted the need for rigorous validation in which pepsin concentrations are corroborated by a secondary quantitative assay, and reflux is confirmed or excluded by multichannel intraluminal impedance pH testing. Standards for sample collection and storage, and normative and pathological values are lacking.

Summary
Progress continues to be made in our understanding of pepsin-mediated damage with implications for novel therapeutic strategies. Salivary pepsin diagnostics continue to garner interest; however, further work appears necessary to improve their accuracy and reproducibility.