bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skeletal muscle (dys)function in heart failure with preserved ejection fraction
Authors: Saw Eng Leng , Ramachandran Swetha , Valero-Muñoz Maria , Sam Flora 
Published: December 2020

Purpose of review
Skeletal muscle dysfunction contributes to exercise intolerance, which manifests as dyspnea and fatiguability in patients with heart failure with preserved ejection fraction (HFpEF). This review aims to summarize the current understanding of skeletal muscle dysfunction in HFpEF.

Recent findings
Animal and human studies in HFpEF provide insights into the pathophysiological alterations in skeletal muscle structure and function with the identification of several molecular mechanisms. Exercise training and novel pharmacological therapies that target skeletal muscle are proposed as therapeutic interventions to treat HFpEF.

Summary
There is evidence that skeletal muscle dysfunction plays a pathophysiological role in HFpEF. However, precise mechanistic insights are needed to understand the contribution of skeletal muscle dysfunction in HFpEF.
COVID-19 myocarditis and long-term heart failure sequelae
Authors: Liu Jing , Deswal Anita , Khalid Umair 
Published: December 2020

Purpose of review
The clinical syndrome of coronavirus disease 2019 (COVID-19) has become a global pandemic leading to significant morbidity and mortality. Cardiac dysfunction is commonly seen in these patients, often presenting as clinical heart failure. Accordingly, we aim to provide a comprehensive review on COVID-19 myocarditis and its long-term heart failure sequelae.

Recent findings
Several suspected cases of COVID-19 myocarditis have been reported. It is often not clear if the acute myocardial dysfunction is caused by myocarditis or secondary to generalized inflammatory state of cytokine release or microvascular thrombotic angiopathy. Ischemia may also need to be ruled out. Regardless, myocardial dysfunction in these patients is associated with poor overall prognosis. Laboratory testing, echocardiography, cardiac magnetic resonance imaging, and even endomyocardial biopsy may be needed for timely diagnosis. Several treatment strategies have been described, including both supportive and targeted therapies.

Summary
COVID-19 can cause a spectrum of ventricular dysfunction ranging from mild disease to fulminant myocarditis with hemodynamic instability. Future research is needed to understand the true prevalence of COVID-19 myocarditis, as well as to better define various diagnostic protocols and treatment strategies.
Pulmonary hypertension in heart failure
Authors: Duran Antonio , Mandras Stacy 
Published: December 2020

Purpose of review
Pulmonary hypertension (PH) occurs frequently in heart failure (HF) and confers worse prognosis. It becomes important to adequately identify these patients to optimize treatment. The purpose of this review is to inform about the updated classification of PH in left heart disease, in addition to current and upcoming trials regarding treatment.

Recent findings
The updated classification of PH due to left heart disease now utilizes pulmonary vascular resistance instead of diastolic pulmonary gradient to differentiate between isolated postcapillary and combined pre and postcapillary PH. In regards to treatment, recent clinical trials continue to provide data that pulmonary vasodilators do not improve outcomes in this population.

Summary
Management of underlying heart disease and optimal control of comorbidities continues to be the mainstay of treatment in PH due to HF. At this time, current data does not support the use of PH-directed therapies.
REPEATABILITY OF CHOROIDAL VASCULARITY INDEX MEASUREMENTS USING DIRECTIONAL OPTICAL COHERENCE TOMOGRAPHY IMAGES
Authors: Ersoz Mehmet Giray , Kesim Cem , Karslioglu Melisa Zisan , Yildiz-Tas Ayse , Hasanreisoglu Murat , Sahin Afsun 
Published: December 2020

Purpose:
To investigate the repeatability of choroidal vascularity index (CVI) measurements in centered and decentered (regarding pupil entry position of the beam) directional subfoveal optical coherence tomography (OCT) scans with (CVI1) and without (CVI2) brightness adjustment.

Methods:
Thirty-two eyes of 32 healthy volunteers were included in this prospective study. First, the fovea was evaluated by a single horizontal enhanced depth imaging OCT scan in a centered direction. Then, the same subfoveal horizontal line was scanned in a decentered direction. The agreement between CVIs obtained from these centered and decentered directional OCT scans was investigated using Bland–Altman analysis and intraclass correlation coefficient.

Results:
Intraclass correlation coefficient between centered and decentered CVI1 was 0.71 (95% CI: 0.48–0.85, P value < 0.001). Intraclass correlation coefficient between centered and decentered CVI2 was 0.73 (95% CI: 0.5–0.86, P value < 0.001). The mean difference between centered and decentered directional measurements for CVI1 and CVI2 were 0.5 and 0.8, respectively.

Conclusion:
There is moderate agreement between CVIs obtained from centered and decentered directional single OCT scans of the same subfoveal area. Studies investigating choroidal vascularity should be standardized by using the same OCT beam direction in all scans.
Recent insights into low-density lipoprotein metabolism and therapy
Authors: Pirillo Angela , Catapano Alberico L. , Norata Giuseppe D. 
Published: December 2020

Purpose of review
Elevated levels of low-density lipoprotein cholesterol (LDL-C) are causal to atherosclerosis and, thus, the reduction of LDL-C represents a major objective for the prevention of cardiovascular disease. Aim of this review is to provide an overview on novel strategies to lower LDL-C.

Recent findings
Although inhibiting liver cholesterol biosynthesis by statins is used as the main therapeutic approach to increase hepatic LDL-receptor expression and lower plasma cholesterol levels, novel insights into lipid and lipoprotein biology have led to the development of additional lipid-lowering therapies that can be used in combination with or as an alternative to statins in patients with statin-intolerance. New approaches include bempedoic acid, proprotein convertase subtilisin/kexin type 9 inhibitors, and angiopoietin-like protein 3 inhibitors.

Summary
In the last decade, several novel therapeutic approaches have been tested and some of them have been approved as lipid-lowering agents. Some drugs are already available in clinical practice, whereas others are at late stages of development.
Energy expenditure and delivery: does the Micawber principle apply during critical illness?
Authors: Frankenfield David C. , Pearson Keith E. 
Published: December 2020

Purpose of review
To determine from existing literature if achieving energy balance in critically ill patients improves outcome. Only randomized clinical trials were considered. Furthermore, the intent had to be that energy intake of the treatment group would reach 100% of requirement, and that the requirement was measured and not estimated.

Recent findings
Six studies meeting the above criteria were identified. Truly positive energy balance was rarely achieved in these studies and protein intake was a confounder because it often varied with the energy intake. The two studies in which energy balance came closest to 100% did suggest clinical benefit, but in both of these studies protein intake was also higher in the high-energy intake group.

Summary
The question posed cannot be fully answered based on the available literature. There are some signals that the pursuit of energy balance in critically ill patients might be favorable, but significant uncertainty remains.
Pediatric Patients’ and Parents’ Perspectives of Unsedated Transnasal Endoscopy in Eosinophilic Esophagitis
Authors: Scherer Corey , Sosensky Peri , Schulman‐Green Dena , Levy Meredith , Smith Clinton , Friedlander Joel , Koral Alex 
Published: December 2020

ABSTRACTBackground:Eosinophilic esophagitis is an increasingly common inflammatory disease of the esophagus. Diagnosis and management are based on the histological presence of eosinophils in the esophageal mucosa, often requiring multiple endoscopies with sedation. Unsedated transnasal endoscopy (TNE), an alternative method of assessing the mucosa without the risks of sedation, is now being performed in the pediatric population. This is the first qualitative study on pediatric patients’ and parents’ experiences with TNE.Objective:The objective of the study was to describe pediatric patients’ and parents’ experiences of TNE with the goal of refining TNE protocols to improve the clinical experience.Methods:We used a qualitative descriptive approach that included in‐depth, semistructured interviews with patients and parents following completion of TNE. Interviews continued until we reached thematic saturation. We analyzed data using qualitative content analysis.Results:A total of 21 interviews were completed. We identified 4 themes: Appeal of TNE; Expectations and Preparation for TNE; Tolerance of TNE; and Evaluation of TNE. Perceived positive aspects of TNE were no exposure to intravenous anesthesia; helpful and clear preparation for the procedure with a demonstration video and physician phone call; distraction during TNE with virtual reality goggles and a stress ball; parent able to accompany the patient; and TNE requiring less time than an esophagogastroduodenoscopy. Negative aspects included patient stress before TNE, patient dislike of nasal spray taste and sensation, and discomfort during the TNE procedure.Conclusion:The overall perception of TNE among our participants was positive. Study data will allow pediatric gastroenterologists the opportunity to improve both preparation for and comfort during TNE.
Type 2 Immunity and Age Modify Gene Expression of Coronavirus-induced Disease 2019 Receptors in Eosinophilic Gastrointestinal Disorders
Authors: Chiang Austin W.T. , Duong Loan D. , Shoda Tetsuo , Nhu Quan M. , Ruffner Melanie , Hara Takeo , Aaron Bailey , Joplin Erik , Manresa Mario C. , Abonia J. Pablo , Dellon Evan S , Hirano Ikuo , Gonsalves Nirmala , Gupta Sandeep K. , Furuta Glenn T. , Rothenberg Marc E. , Lewis Nathan E. , Muir Amanda B. , Aceves Seema S. 
Published: December 2020

ABSTRACTInfection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can lead to coronavirus-induced disease 2019 (COVID-19). The gastrointestinal (GI) tract is now an appreciated portal of infection. SARS-CoV-2 enters host cells via angiotensin-converting enzyme-2 (ACE2) and the serine protease TMPRSS2. Eosinophilic gastrointestinal disorders (EGIDs) are inflammatory conditions caused by chronic type 2 (T2) inflammation. the effects of the T2 atopic inflammatory milieu on SARS-COV-2 viral entry gene expression in the GI tract is poorly understood. We analyzed tissueACE2andTMPRSS2gene expression in pediatric eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), and in normal adult esophagi using publicly available RNA-sequencing datasets. Similar to findings evaluating the airway, there was no difference in tissue ACE2/TMPRSS2 expression in EoE or EG when compared with control non-EoE/EG esophagus/stomach.ACE2gene expression was significantly lower in esophagi from children with or without EoE and from adults with EoE as compared with normal adult esophagi. Type 2 immunity and pediatric age could be protective for infection by SARS-CoV-2 in the gastrointestinal tract because of decreased expression of ACE2.
Intestinal Microbiome in Preterm Infants Influenced by Enteral Iron Dosing
Authors: Ho Thao , Sarkar Anujit , Szalacha Laura , Groer Maureen W. 
Published: December 2020

ABSTRACT

Objectives:
The aim of the study was to compare the intestinal microbiome in very low birth weight (VLBW) infants who received different enteral iron supplementation (EIS) doses.

Study Design:
Longitudinal stool collection in 80 VLBW infants were conducted up to 2 months postnatally in a prospective study. The 16S rRNA regions V4 was used to calculate microbiome compositions and the Piphillin software was used for bacterial functional prediction. Linear mixed effect models and Wilcoxon rank-sum tests were performed to examine the relationships between initial EIS dosage and stool microbiome and bacterial functional potential.

Results:
There were 105 samples collected before and 237 collected after EIS started from infants with birth gestational age and weight of 28.1 ± 2.4 weeks and 1103 ± 210 g, respectively. The average postnatal age at start of EIS was 17.9 ± 6.9 days and the average initial EIS dose was 4.8 ± 1.1 mg · kg−1 · day−1. Infants who were started on ≥6 mg · kg−1 · day−1 had higher abundances of Proteus and Bifidobacterium and a lower alpha diversity than those started on lower doses (P < 0.05). Infants given higher EIS doses had higher bacterial predicted functional potentials for ferroptosis and epithelial invasion after 2 weeks post EIS.

Conclusions:
Higher EIS dosage is linked to higher abundances of Proteus and Bifidobacterium, and a less diverse microbiome and higher predicted potential of bacterial epithelial invasion. These observational findings should be further studied in a randomized study to elucidate the optimal dosage of EIS in VLBW infants.
Effect of Low-Frequency rTMS and Intensive Speech Therapy Treatment on Patients With Nonfluent Aphasia After Stroke
Authors: Bai Guangtao , Jiang Liang , Ma Wenshuai , Meng Pingping , Li Jiang , Wang Yuyang , Wang Qiang 
Published: December 2020

Background:
To observe the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on patients with nonfluent aphasia after stroke.

Materials and Methods:
Thirty patients were divided into control, rTMS, and 2 times a day low-frequency rTMS (2rTMS) groups, and all 3 groups had intensive speech therapy (ST). Patients were assessed by western aphasia battery (WAB) scale. The spontaneous language, listening comprehension, retelling, and naming were scored, respectively. The expression of brain-derived neurotrophic factor (BDNF) in peripheral blood was detected by enzyme-linked immunosorbent assay.

Results:
There was significant difference in aphasia quotient after treatment in the 3 groups. The values of the 4 dimensions in the WAB score of the rTMS group were higher than those in the control group. The WAB scores in the 2rTMS group were higher than those in the rTMS group. After 2 weeks treatment, the BDNF levels in the rTMS group and the 2rTMS group were significantly higher than those in the control group. Four weeks later, the 2rTMS group was significantly increased compared with the control group and the rTMS group.

Conclusions:
Low-frequency rTMS combined with conventional ST treatment can effectively improve the language function of patients with nonfluent aphasia after stroke. Two times a day low-frequency rTMS therapy combined with conventional ST treatment can improve the language function of patients with nonfluent aphasia after stroke more effectively and it also promote the expression of BDNF more effectively, thereby improving nerve repair and protecting brain tissue.
Diagnostic Accuracy of the INSHI Consensus Case Definition for the Diagnosis of Paradoxical Tuberculosis-IRIS
Authors: Stek Cari , Buyze Jozefien , Menten Joris , Schutz Charlotte , Thienemann Friedrich , Blumenthal Lisette , Maartens Gary , Boyles Tom , Wilkinson Robert J. , Meintjes Graeme , Lynen Lutgarde 
Published: December 2020

Background:
The diagnosis of paradoxical tuberculosis–associated immune reconstitution inflammatory syndrome (TB-IRIS) relies on characteristic clinical features synthesized as the International Network for the Study of HIV-associated IRIS (INSHI) case definition. There is no confirmatory laboratory test.

Setting:
Site B HIV-TB clinic in Khayelitsha, Cape Town, South Africa.

Methods:
Using data of participants with HIV-associated tuberculosis starting antiretroviral treatment from a prospective trial evaluating prednisone for TB-IRIS prevention, we applied latent class analysis to model a gold standard for TB-IRIS. The model-predicted probability of TB-IRIS for each participant was used to assess the performance of the INSHI case definition and compare its diagnostic accuracy with several adapted case definitions.

Results:
Data for this analysis were complete for 217 participants; 41% developed TB-IRIS. Our latent class model included the following parameters: respiratory symptoms; night sweats; INSHI major criteria 1, 2, and 4; maximum C-reactive protein >90 mg/L; maximum heart rate >120/min; maximum temperature >37.7°C; and preantiretroviral therapy CD4 count <50 cells/µL. The model estimated a TB-IRIS incidence of 43% and had optimal goodness of fit (χ2 = 337, P = 1.0). The INSHI case definition displayed a sensitivity of 0.77 and a specificity of 0.86. Replacing all the minor INSHI criteria with objectives measures (C-reactive protein elevation, fever, and/or tachycardia) resulted in a definition with better diagnostic accuracy, with a sensitivity of 0.89 and a specificity of 0.88.

Conclusion:
The INSHI case definition identifies TB-IRIS with reasonable accuracy. Amending the case definition by replacing INSHI minor criteria with objective variables improved sensitivity without loss of specificity.
The Effect of Mycophenolate Mofetil as First-Line Therapy on the Timing of Urine Protein–to–Creatinine Ratio Reduction in Immunosuppressant-Naive Patients With Lupus Nephritis at a Single Center
Authors: Timlin Homa , Hardenbergh Dylan , Fine Derek , Monroy-Trujillo Jose Manuel , Haque Uzma , Adler Brittany , Vaidya Dhananjay , Geetha Duvuru 
Published: December 2020

Background/Objectives
Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis (LN). The purpose of this study was to assess the effect of mycophenolate mofetil (MMF) on the timing of urine protein–to–creatinine ratio reaching 200 mg or less after starting MMF as initial therapy for class III, IV, or V in immunosuppressant-naive patients with LN.

Methods
Patients who had a diagnosis of biopsy-proven LN were included in this cohort study. The initial dose of MMF was 1000 mg twice daily. If no improvement, it was increased to 1500 mg twice daily after 1 month. For statistical analysis, exact binomial distribution 95% confidence intervals were calculated.

Results
Nine patients were identified. There were 3 patients with class III, 3 with class IV, 1 with class III to V, 1 with class II to V, and 1 with class V lupus nephritis. The majority were African Americans (70%). At baseline, proteinuria ranged between 0.41 and 4 g, and 88% had normal estimated glomerular filtration rate. Forty-four percent of patients reached 0.28 g of proteinuria within 8 weeks of starting MMF (95% confidence interval, 14%–79%), all of which maintained the same level of response and normal estimated glomerular filtration rate at 12 months. Thirty-three percent of patients achieved the American College of Rheumatology complete response at 8 weeks.

Conclusions
This study demonstrates that only a minority of immunosuppressant-naive LN patients achieved the American College of Rheumatology complete response at 8 weeks after initiation of MMF. A rapid decline in the proteinuria to 0.28 g within the first 8 weeks of the treatment correlated strongly with achieving the same level of response at 12 months.
The Impact of Biologic Drugs on High-Density Lipoprotein Cholesterol Efflux Capacity in Rheumatoid Arthritis Patients
Authors: Cacciapaglia Fabio , Perniola Simone , Venerito Vincenzo , Anelli Maria Grazia , Härdfeldt Jennifer , Fornaro Marco , Moschetta Antonio , Iannone Florenzo 
Published: December 2020

Background
One of the most intriguing conundrums in patients with rheumatoid arthritis (RA) is the lack of correlation between cholesterol levels and cardiovascular (CV) events, diminishing the reliability of plasmatic lipid levels in estimating the CV risk. High-density lipoprotein cholesterol efflux capacity (HDLc-EC) directly indicates the functional ability of HDL to scavenge cholesterol from vascular wall and may provide better information on the atherogenic risk. The aim of this study was to examine the effects of different disease-modifying antirheumatic drugs on HDLc-EC in RA.

Methods
Consecutive RA patients treated with different biologic disease-modifying antirheumatic drugs or methotrexate monotherapy were longitudinally observed. Demographic and clinical features as well as lipid profile were recorded at baseline, 24-week, and 52-week follow-up. At the same time points, HDLc-EC was evaluated using J771 macrophages and a fluorometric assay.

Results
We analyzed 100 RA patients on methotrexate, infliximab, tocilizumab, abatacept, or rituximab. No significant changes in the lipoprotein levels were detected, whereas the mean HDLc-EC statistically increased from baseline (22.5% ± 4.8%) to 24 weeks (24.5% ± 5.7%; p < 0.001) and 52 weeks (25.1% ± 5.9%; p < 0.001). Patients on tocilizumab showed the highest increase in HDLc-EC, already at 24 weeks. Patients on treatment with infliximab or rituximab showed a significant increase in HDLc-EC at 52 weeks. No significant changes were detected in abatacept and methotrexate groups.

Conclusions
Some treatments may impact cholesterol reverse transport in RA. The improved HDLc-EC, independently from lipid levels, may be one of the missing links between inflammation, lipids, and CV risk in RA.
First Biologic Drug Persistence in Patients With Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis
Authors: Ngo Minh-Duc , Zummer Michel , Andersen Kathleen M. , Richard Nicolas 
Published: December 2020

Background/Objectives
Axial spondyloarthritis (axSpA) includes ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA). Both are managed with biologic therapies; however, there is a lack of evidence for nr-axSpA therapies. The primary objective was to compare persistence to first biologic between AS and nr-axSpA patients in a longitudinal cohort. Secondary objectives were to examine disease activity markers over time and to evaluate predictors for drug discontinuation.

Methods
Data were obtained from persons enrolled in the SpondyloArthritis Research Consortium of Canada registry between 2003 and 2018. Kaplan-Meier curves were constructed from the time of biologic initiation until discontinuation and compared using the log-rank test. Subanalyses were performed according to calendar year and disease activity. Cox proportional hazards models were used to identify factors associated with discontinuation.

Results
We identified 385 biologic-naive persons. Overall, the 349 AS participants had longer persistence to their first biologic than the 36 nr-axSpA subjects (p < 0.01). The Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index decreased by 2.3 points (95% confidence interval [CI], 1.9–2.7) and 3.2 points (95% CI, 2.6–3.7), respectively, in the first year and were stable thereafter. Adjusting for sex, human leukocyte antigen B27, and smoking status, nr-axSpA patients were more likely to discontinue their biologic than AS patients (hazards ratio, 1.65; 95% CI, 1.03–2.62).

Conclusions
In this real-world study, AS patients had longer persistence to their first biologic compared with nr-axSpA, with disease subtype being the most significant predictor of treatment persistence. Future studies should be targeted at assessing long-term clinical outcome of axSpA in the real-world setting.