bluuebunny/crossref_metadata_2025 huggingface dataset:
Responses of functional traits to seven-year nitrogen addition in two tree species: coordination of hydraulics, gas exchange and carbon reserves
Authors: Zhang Hongxia , Yuan Fenghui , Wu Jiabing , Jin Changjie , Pivovaroff Alexandria L , Tian Jinyuan , Li Weibin , Guan Dexin , Wang Anzhi , McDowell Nate G
Published: September 2020

Atmospheric nitrogen (N) deposition has been observed to impact plant structure and functional traits in terrestrial ecosystems. Although the effect of N deposition on plant water use has been well-evaluated in laboratories and in experimental forests, the linkages between water and carbon relations under N deposition are unclear. Here, we report on hydraulics, gas exchange and carbon reserves of two broad-leaved tree species (Quercus mongolica and Fraxinus mandshurica) in mature temperate forests after a seven-year experiment with different levels of N addition (control (CK), low (23 kg N ha−1 yr−1), medium (46 kg N ha−1 yr−1) and high (69 kg N ha−1 yr−1)). We investigated variation in hydraulic traits (xylem-specific hydraulic conductivity (Ks), native percentage loss of conductivity (PLC) and leaf water potential), xylem anatomy (vessel diameter and density), gas exchange (maximum net photosynthesis rate and stomatal conductance) and carbon reserves (soluble sugars, starch and total nonstructural carbohydrates (NSC)) with different N addition levels. We found that medium N addition significantly increased Ks and vessel diameter compared to control, but accompanied increasing PLC and decreasing leaf water potential, suggesting that N addition results in a greater hydraulic efficiency and higher risk of embolism. N addition promoted photosynthetic capacity via increasing foliar N concentration but did not change stomatal conductance. In addition, we found increase in foliar soluble sugar concentration and decrease in starch concentration with N addition, and positive correlations between hydraulic traits (vessel diameter and PLC) and soluble sugars. These coupled responses of tree hydraulics and carbon metabolism are consistent with a regulatory role of carbohydrates in maintaining hydraulic integrity. Our study provides an important insight into the relationship of plant water transport and carbon dynamics under increasing N deposition.
Chlorophyll fluorescence parameters, leaf traits and foliar chemistry of white oak and red maple trees in urban forest patches
Authors: Sonti Nancy F , Hallett Richard A , Griffin Kevin L , Trammell Tara L E , Sullivan Joe H
Published: September 2020

The provisioning of critical ecosystem services to cities of the eastern USA depends on the health and physiological function of trees in urban areas. Although we know that the urban environment may be stressful for trees planted in highly developed areas, it is not clear that trees in urban forest patches experience the same stressful environmental impacts. In this study, we examine chlorophyll fluorescence parameters, leaf traits, foliar nutrients and stable isotope signatures of urban forest patch trees compared with trees growing at reference forest sites, in order to characterize physiological response of these native tree species to the urban environment of three major cities arranged along a latitudinal gradient (New York, NY; Philadelphia, PA; Baltimore, MD). Overall, white oaks (Quercus alba L.) show more differences in chlorophyll fluorescence parameters and leaf traits by city and site type (urban vs reference) than red maples (Acer rubrum L.). The exceptions were δ13C and δ15N, which did not vary in white oak foliage but were significantly depleted (δ13C) and enriched (δ15N) in urban red maple foliage. Across all sites, red maples had higher thermal tolerance of photosynthesis (Tcrit) than white oaks, suggesting a greater ability to withstand temperature stress from the urban heat island effect and climate change. However, the highest average values of Tcrit were found in the Baltimore urban white oaks, suggesting that species suitability and response to the urban environment varies across a latitudinal gradient. Stomatal pore index (SPI) showed inter-specific differences, with red maple SPI being higher in urban trees, whereas white oak SPI was lower in urban trees. These results demonstrate that differences in native tree physiology occur between urban and reference forest patches, but they are site- and species-specific. Data on local site characteristics and tree species performance over time remain necessary to gain insight about urban woodland ecosystem function.
The cold truth about postcardiac arrest targeted temperature management
Authors: Knippa Sara , Butler Jana , Johnson Lauren , Perman Sarah M.
Published: September 2020

This article provides nurses with up-to-date evidence to empower them in contributing to the 33°C versus 36°C discussion in postcardiac arrest targeted temperature management (TTM). Presented in debate format, this article addresses the pros and cons of various target temperatures, examines the evidence around TTM, and applies it to clinical scenarios.
Fractures in Patients With COVID-19 Infection: Early Prognosis and Management. A Case Series of 20 Patients in a Single Institution in Lombardy, Northern Italy
Authors: Jannelli Eugenio , Castelli Alberto , Ferranti Calderoni Enrico , Annunziata Salvatore , Maccario Gaia , Ivone Alessandro , Pasta Gianluigi , Mosconi Mario
Published: September 2020

Fifty-eight percent of the total infections in Italy of COVID-19 were found in northern Italy, in particular, Lombardy. From February 21, 2020, to March 23, 2020, 20 patients with a fracture and a diagnosis of COVID-19 were hospitalized. Demographic data, COVID-19 symptoms, laboratory and radiographic examinations, and treatment methods were recorded. At 1-month follow-up, patients were assessed with the SF-36 score. This case series includes 20 patients (16 women and 4 men), with an average age of 82.35 years (range 59–95). Eleven patients (55%) had a femur fracture. Fourteen patients (70%) had 3 or more comorbidities or previous pathologies. Three patients with severe comorbidities died during the hospitalization. Thirteen patients (65%) had fever, 18 patients (90%) asthenia, and 17 patients (85%) dyspnea. All patients (100%) were given antibiotic therapy, whereas 16 patients (80%) underwent hydroxychloroquine therapy and 8 (40%) were treated with corticosteroids. Eighteen patients (90%) underwent antithromboembolic prophylaxis. Eighteen patients (90%) had lymphopenia. All 20 patients (100%) required noninvasive mechanical ventilation. High D-dimer and polymerase chain reaction values were found in all patients (100%), whereas lactate dehydrogenase was increased in 18 patients (90%). Patients with fractures, especially in the lower limbs, frequently require hospitalization, making these patients more subjected to the risk of COVID-19 infection. COVID-19 infection therefore does not seem to influence the fracture pattern in the elderly population but can lead to health deterioration with increased mortality. The typical symptoms of COVID-19 disease have not changed when associated with a fracture or trauma. Laboratory data are in line with what is reported in recent studies, whereas a more invasive assisted ventilation is associated with a poor prognosis. Finally, analyzing the data obtained from the SF-36 score, significantly lower values emerged when compared with those reported in the literature.

Level of Evidence:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Early Orthopaedic Trauma Outcomes in COVID-19 Infected Patients: A Case Series
Authors: Edwards Diep N. , Arguello Alexandra M. , Ponce Brent A. , Spitler Clay A. , Quade Jonathan H.
Published: September 2020

Orthopaedic trauma presents a unique and complex challenge in the initial phase of the coronavirus 2019 (COVID-19) global crisis. Little is currently known about the surgical practices in orthopaedic emergencies in the early days of the COVID-19 outbreak (1). This is a retrospective case series of 10 orthopaedic trauma patients who underwent fracture fixation in March 2020. Of the 10 patients testing COVID-19 positive, there were a total of 16 long bone fractures, 5 pelvic ring fractures, and 1 lumbar burst fracture. There were 7 (70%) males in this cohort. Two (20%) of the COVID-positive patients did not develop fever, leukocytosis, respiratory insufficiency, or positive imaging findings and were younger (average age 25.5 years) with fewer comorbidities (average 0.5) compared with the 8 symptomatic COVID-19–positive patients (56.6 years with 1.88 comorbidities). Advancement of COVID-19 pathogenesis with lung opacities and prolonged intubation occurred in all 5 patients who remained on ventilation postoperatively (range 9 hours–11 days). At the time of most recent follow-up, all patients survived, 1 continues to require ventilation support, 1 remains admitted without ventilation support, and 8 (80%) were discharged to home.

Level of Evidence:

Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
The Association of Inflammatory Cytokines in the Pulmonary Pathophysiology of Respiratory Failure in Critically Ill Patients With Coronavirus Disease 2019
Authors: Stukas Sophie , Hoiland Ryan L. , Cooper Jennifer , Thiara Sonny , Griesdale Donald E. , Thomas Adam D. , Orde Matthew M. , English John C. , Chen Luke Y. C. , Foster Denise , Mitra Anish R. , Romano Kali , Sweet David D. , Ronco Juan J. , Kanji Hussein D. , Chen Yu-Wei R. , Wong Sophia L. , Wellington Cheryl L. , Sekhon Mypinder S.
Published: September 2020

Objectives:

The majority of coronavirus disease 2019 mortality and morbidity is attributable to respiratory failure from severe acute respiratory syndrome coronavirus 2 infection. The pathogenesis underpinning coronavirus disease 2019-induced respiratory failure may be attributable to a dysregulated host immune response. Our objective was to investigate the pathophysiological relationship between proinflammatory cytokines and respiratory failure in severe coronavirus disease 2019.

Design:

Multicenter prospective observational study.

Setting:

ICU.

Patients:

Critically ill patients with coronavirus disease 2019 and noncoronavirus disease 2019 critically ill patients with respiratory failure (ICU control group).

Interventions:

Daily measurement of serum inflammatory cytokines.

Measurements and Main Results:

Demographics, comorbidities, clinical, physiologic, and laboratory data were collected daily. Daily serum samples were drawn for measurements of interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α. Pulmonary outcomes were the ratio of Pao
2/Fio
2 and static lung compliance. Twenty-six patients with coronavirus disease 2019 and 22 ICU controls were enrolled. Of the patients with coronavirus disease 2019, 58% developed acute respiratory distress syndrome, 62% required mechanical ventilation, 12% underwent extracorporeal membrane oxygenation, and 23% died. A negative correlation between interleukin-6 and Pao
2/Fio
2 (rho, –0.531; p = 0.0052) and static lung compliance (rho, –0.579; p = 0.033) was found selectively in the coronavirus disease 2019 group. Diagnosis of acute respiratory distress syndrome was associated with significantly elevated serum interleukin-6 and interleukin-1β on the day of diagnosis.

Conclusions:

The inverse relationship between serum interleukin-6 and Pao
2/Fio
2 and static lung compliance is specific to severe acute respiratory syndrome coronavirus 2 infection in critically ill patients with respiratory failure. Similar observations were not found with interleukin-β or tumor necrosis factor-α.
Clinical Practice Guidelines for Early Mobilization in the ICU: A Systematic Review
Authors: Lang Jenna K. , Paykel Melanie S. , Haines Kimberley J. , Hodgson Carol L.
Published: September 2020

Objectives:

To evaluate the methodological quality and thematic completeness of existing clinical practice guidelines, addressing early mobilization of adults in the ICU.

Data Sources:

Systematic review of Medline, Embase, CINAHL, Cochrane, and grey literature from January 2008 to February 2020.

Study Selection:

Two reviewers independently screened titles and abstracts and then full texts for eligibility. Ten publications were included.

Data Extraction:

A single reviewer extracted data from the included publications and a second reviewer completed cross-checking. Qualitative data were extracted in five categories relating to the key factors influencing delivery of early mobilization to critically ill patients.

Data Synthesis:

Methodological quality was appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Appraisal of Guidelines for Research and Evaluation II scores for applicability were low. Median quality scores for editorial independence, rigor of development, and stakeholder engagement were also poor. Narrative synthesis of publication content was undertaken. All publications supported implementation of early mobilization. Most documents agreed upon seven topics: 1) early mobilization is safe and may reduce healthcare costs, 2) safety criteria should be provided, 3) a protocolized or structured approach should be used, 4) collaborative teamwork is required, 5) staff require specific skills or experience, 6) patient and family engagement is important, and 7) program evaluation and outcome measurement are a key component of implementation. There was no consensus on dosage and patient selection. The areas of team culture and leadership were poorly addressed.

Conclusions:

Despite significant variation in the methodological quality of clinical practice guidelines for early mobilization, there were important consistencies in recommendations internationally. Future research should address gaps related to patient selection, dosage, team culture, and expertise. Future clinical practice guidelines in this area should focus on engagement of patients and families in the development process and provision of resources to support implementation based on the consideration of known barriers and facilitators.
High-Flow Nasal Cannula Compared With Conventional Oxygen Therapy or Noninvasive Ventilation Immediately Postextubation: A Systematic Review and Meta-Analysis
Authors: Granton David , Chaudhuri Dipayan , Wang Dominic , Einav Sharon , Helviz Yigal , Mauri Tommaso , Mancebo Jordi , Frat Jean-Pierre , Jog Sameer , Hernandez Gonzalo , Maggiore Salvatore M. , Hodgson Carol L. , Jaber Samir , Brochard Laurent , Trivedi Vatsal , Ricard Jean-Damien , Goligher Ewan C. , Burns Karen E. A. , Rochwerg Bram
Published: September 2020

Objectives:

Reintubation after failed extubation is associated with increased mortality and longer hospital length of stay. Noninvasive oxygenation modalities may prevent reintubation. We conducted a systematic review and meta-analysis to determine the safety and efficacy of high-flow nasal cannula after extubation in critically ill adults.

Data Sources:

We searched MEDLINE, EMBASE, and Web of Science.

Study Selection:

We included randomized controlled trials comparing high-flow nasal cannula to other noninvasive methods of oxygen delivery after extubation in critically ill adults.

Data Extraction:

We included the following outcomes: reintubation, postextubation respiratory failure, mortality, use of noninvasive ventilation, ICU and hospital length of stay, complications, and comfort.

Data Synthesis:

We included eight randomized controlled trials (n = 1,594 patients). Compared with conventional oxygen therapy, high-flow nasal cannula decreased reintubation (relative risk, 0.46; 95% CI, 0.30–0.70; moderate certainty) and postextubation respiratory failure (relative risk, 0.52; 95% CI, 0.30–0.91; very low certainty), but had no effect on mortality (relative risk, 0.93; 95% CI, 0.57–1.52; moderate certainty), or ICU length of stay (mean difference, 0.05 d fewer; 95% CI, 0.83 d fewer to 0.73 d more; high certainty). High-flow nasal cannula may decrease use of noninvasive ventilation (relative risk, 0.64; 95% CI, 0.34–1.22; moderate certainty) and hospital length of stay (mean difference, 0.98 d fewer; 95% CI, 2.16 d fewer to 0.21 d more; moderate certainty) compared with conventional oxygen therapy, however, certainty was limited by imprecision. Compared with noninvasive ventilation, high-flow nasal cannula had no effect on reintubation (relative risk, 1.16; 95% CI, 0.86–1.57; low certainty), mortality (relative risk, 1.12; 95% CI, 0.82–1.53; moderate certainty), or postextubation respiratory failure (relative risk, 0.82; 95% CI, 0.48–1.41; very low certainty). High-flow nasal cannula may reduce ICU length of stay (moderate certainty) and hospital length of stay (moderate certainty) compared with noninvasive ventilation.

Conclusions:

High-flow nasal cannula reduces reintubation compared with conventional oxygen therapy, but not compared with noninvasive ventilation after extubation.
Treatment and Mortality of Hemophagocytic Lymphohistiocytosis in Adult Critically Ill Patients: A Systematic Review With Pooled Analysis
Authors: Knaak Cornelia , Schuster Friederike S. , Nyvlt Peter , Spies Claudia , Feinkohl Insa , Beutel Gernot , Schenk Thomas , La Rosée Paul , Janka Gritta , Brunkhorst Frank M. , Keh Didier , Lachmann Gunnar
Published: September 2020

Objectives:

Hemophagocytic lymphohistiocytosis is a cytokine release syndrome caused by uncontrolled immune activation resulting in multiple organ failure and death. In this systematic review, we aimed to analyze triggers, various treatment modalities, and mortality in critically ill adult hemophagocytic lymphohistiocytosis patients.

Data Sources:

MEDLINE database (PubMed) at October 20, 2019.

Study Selection:

Studies and case series of patients greater than or equal to 18 years old, of whom at least one had to be diagnosed with hemophagocytic lymphohistiocytosis and admitted to an ICU.

Data Extraction:

Source data of studies and case series were summarized and analyzed on an individual basis. Multivariable logistic regression analysis was performed adjusting for age, sex, and trigger groups. Each single treatment agent was entered as a dichotomous variable to determine treatments associated with survival, regardless if given alone or in combination.

Data Synthesis:

In total, 661 patients from 65 studies and case series were included. Overall mortality was 57.8%. Infections were the most frequent trigger (49.9%), followed by malignancies (28.0%), autoimmune diseases (12.1%), unknown triggers (9.4%), and drugs (0.6%). Treatment with IV immunoglobulins was associated with improved survival (odds ratio, 0.548; 95% CI, 0.337–0.891; p = 0.015), while treatment with cyclosporine was associated with increased risk of death (odds ratio, 7.571; 95% CI, 3.702–15.483; p < 0.001). Considering different trigger groups separately, same results occurred only for infection-triggered hemophagocytic lymphohistiocytosis. No information was available on disease severity and other confounding factors.

Conclusions:

Mortality of hemophagocytic lymphohistiocytosis in the ICU is high. Most common triggers were infections. Results of survival analyses may be biased by treatment indication and disease severity. Future studies prospectively investigating treatment tailored to critically ill hemophagocytic lymphohistiocytosis patients are highly warranted.
Variability in the Physiologic Response to Fluid Bolus in Pediatric Patients Following Cardiac Surgery
Authors: Ranjit Suchitra , Natraj Rajeswari , Kissoon Niranjan , Thiagarajan Ravi , Ramakrishnan Balakrishnan , García M. Ignacio Monge
Published: September 2020

Background:

Fluid boluses aiming to improve the cardiac output and oxygen delivery are commonly administered in children with shock. An increased mean arterial pressure in addition to resolution of tachycardia and improved peripheral perfusion are often monitored as clinical surrogates for improvement in cardiac output. The objective of our study is to describe changes in cardiac index, mean arterial pressure, and their relationship to other indices of cardiovascular performance.

Objective:

The objective of our study is to describe changes in cardiac index, mean arterial pressure, and their relationship to other indices of cardiovascular performance.

Design, Setting, Patients, and Interventions:

We prospectively analyzed hemodynamic data from children in the cardiac ICU who received fluid bolus (10mL/kg of Ringers-Lactate over 30 min) for management of shock and/or hypoperfusion within 12h of cardiac surgery. Cardiac index responders and mean arterial pressure-responders were defined as CI ≥10% and mean arterial pressure ≥10%, respectively. We evaluated the gradient for venous-return (mean systemic filling pressure-central venous pressure), arterial load properties (systemic vascular resistance index and elastance index) and changes in vasopressor support after fluid bolus.

Measurements and Main Results:

Fifty-seven children between 1 month and 16 years (median Risk adjustment after congenital heart surgery Model for Outcome Surveillance in Australia and New Zealand score of 3.8 (interquartile range 3.7–4.6) received fluid bolus. Cardiac index-responsiveness and mean arterial pressure-responsiveness rates were 33% and 56%, respectively. No significant correlation was observed between changes in mean arterial pressure and cardiac index (r = 0.035, p = 0.79). Although the mean systemic filling pressure – central venous pressure and the number of cardiac index-responders after fluid bolus were similar, the arterial load parameters did not change in mean arterial pressure-nonresponders. Forty-three patients (75%) had a change in Vasoactive-Inotrope Score after the fluid bolus, of whom 60% received higher level of vasoactive support.

Conclusions:

The mean arterial pressure response to fluid bolus in cardiac ICU patients was unpredictable with a poor relationship between cardiac index-responsiveness and mean arterial pressure-responsiveness. Because arterial hypotension is frequently a trigger for administering fluids and changes in blood pressure are commonly used for tracking changes in cardiac output, we suggest a cautious and individualized approach to repeat fluid bolus based solely on lack of mean arterial pressure response to the initial fluid, since the implications include decreased arterial tone even if the cardiac index increases.
Serum microRNA expression profiling revealing potential diagnostic biomarkers for lung adenocarcinoma
Authors: Shan Xia , Zhang Lan , Zhu Dan-Xia , Zhou Xin , Zhang Huo , Liu Qing-Xie , Tang Jian-Wei , Wen Wei , Wang Tong-Shan , Zhu Wei , Liu Ping
Published: September 2020

Background

Recent studies have demonstrated that microRNAs (miRNAs) in the blood circulation can serve as promising diagnostic markers for cancers. This four-stage study aimed at finding serum miRNAs as potential biomarkers for lung adenocarcinoma (LA) diagnosis.

Methods

The study was carried out between 2016 and 2017. The Exiqon miRNA qPCR panel (3 LA vs. 1 normal control [NC] pooled serum samples) was used for initial screening to acquire miRNA profiles. Thirty-five dysregulated miRNAs were further evaluated in the training (24 LA vs. 24 NCs) and testing stages (110 LA vs. 110 NCs) using quantitative real-time polymerase chain reaction assays.

Results

Four serum miRNAs (miR-133a-3p, miR-584-5p, miR-10b-5p, and miR-221-3p) were significantly overexpressed in LA patients compared with NCs. The diagnostic value of the four-miRNA panel was validated by an external cohort (36 LA vs. 36 NCs). The areas under the receiver operating characteristic curve of the four-miRNA panel in the training, testing, and external validation stages were 0.734, 0.803, and 0.894 respectively. Meanwhile, the expression level of miR-221-3p was much higher in LA tumor samples than that in the adjacent normal tissues (19 LA vs. 19 NCs). The expression level of miR-10b-5p was also elevated in the serum-derived exosomes samples (18 LA vs. 18 NCs). The expression of miR-133a-3p, miR-584-5p, and miR-10b-5p was significantly elevated in LA patients with epidermal growth factor receptor mutation compared with NCs.

Conclusion

The study established a four-miRNA signature in serum that could improve the diagnostic capability of LA.
The Role of Testosterone in Patients With Heart Failure: A Systematic Review
Authors: Park SoEun , Gale Stormi E. , Watson Kristin
Published: September 2020

The consequences of heart failure (HF) remain high despite treatment advances. Deficiency of the anabolic axes is common in HF and is associated with an increased risk of death and worsening functional status. Exogenous testosterone use has been shown to decrease vascular resistance and improve cardiac output. The objective of this systematic review was to assess the efficacy (mortality, hospitalization, cardiac function, and quality of life) and safety of testosterone in HF patients. The Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines were followed. Four electronic databases were searched from inception until November 30, 2019. The initial search yielded 1308 articles, and 10 randomized controlled trials with exogenous testosterone in patients with HF were included after exclusion criteria were applied. One study evaluated the impact of testosterone on mortality and HF hospitalization; no difference was observed compared with placebo. In 5 studies, testosterone use was associated with an improvement in walking distance. In 1 of the 2 studies that evaluated functional status, New York Heart Association class was improved. In 2 out of 4 studies, quality of life was improved with therapy. When reported, testosterone use was not associated with an increase in side effects. Overall, testosterone use has not been shown to reduce the risk of death or HF hospitalization, with inconsistent evidence on the impact of therapy on quality of life. Additional trials are needed before testosterone can be recommended. Patients with HF should receive guideline-directed medical therapy with the assurance that patients are receiving maximum tolerated doses.
Double Genetic Hit: Fragile X Syndrome and Partial Deletion of Protein Patched Homolog 1 Antisense as Cause of Severe Autism Spectrum Disorder
Authors: Saldarriaga Wilmar , Payán-Gómez César , González-Teshima Laura Yuriko , Rosa Lina , Tassone Flora , Hagerman Randi J.
Published: September 2020

Background:

Fragile X syndrome (FXS) is an X-linked genetic disorder caused by the absence of the fragile X mental retardation 1 protein. FXS is the most common inherited cause of intellectual disability and autism spectrum disorder (ASD). Approximately 60% of subjects with FXS present with ASD, and 2% to 4% of individuals diagnosed with ASD have FXS. Most individuals with ASD have a genetic disorder, so detailed molecular testing of individuals with ASD is medically indicated. Deletions of the protein patched homolog 1 antisense (PTCHD1-AS) gene have been associated with ASD. Here, we describe, for the first time, a boy with FXS because of a point mutation in the FMR1 gene and autism, and the latter comorbidity of ASD is likely because of a deletion of PTCHD1-AS. Thus, the observed phenotype of FXS with severe autism symptoms is likely caused by a double hit of genetic mutations.

Case Presentation:

The case is a 5-year-old boy with phenotypic characteristics of FXS. The psychological assessment based on parent report and the Autism Diagnostic Observation Schedule, Second Edition identified severe difficulties on every item of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnostic criteria for ASD, with language impairment, anxiety, attention, and affective problems. Exome sequencing identified a de novo pathogenic variant in the FMR1 gene c.229delT (p.Cys77Alafs*5) and, coupled with comparative genomic hybridization, also diagnosed a maternally inherited partial deletion of the PTCHD1-AS gene.

Conclusion:

Fragile X syndrome presents with clinical features in virtually all affected men, predominantly intellectual disability. However, there are other comorbidities present in a subset of patients, including ASD. We propose that the variable expressivity in FXS could be partially explained by the additive effect of a second genetic mutation that increases the individual susceptibility to the unique phenotypic findings, as is the case of the patient described here.
Impact of Regression to the Mean on the Synthetic Control Method
Authors: Illenberger Nicholas A. , Small Dylan S. , Shaw Pamela A.
Published: September 2020

To make informed policy recommendations from observational panel data, researchers must consider the effects of confounding and temporal variability in outcome variables. Difference-in-difference methods allow for estimation of treatment effects under the parallel trends assumption. To justify this assumption, methods for matching based on covariates, outcome levels, and outcome trends—such as the synthetic control approach—have been proposed. While these tools can reduce bias and variability in some settings, we show that certain applications can introduce regression to the mean (RTM) bias into estimates of the treatment effect. Through simulations, we show RTM bias can lead to inflated type I error rates and bias toward the null in typical policy evaluation settings. We develop a novel correction for RTM bias that allows for valid inference and show how this correction can be used in a sensitivity analysis. We apply our proposed sensitivity analysis to reanalyze data concerning the effects of California’s Proposition 99, a large-scale tobacco control program, on statewide smoking rates.
Prognostic Value of NT-Pro Brain Natriuretic Peptide During Exercise Recovery in Ischemic Heart Failure of Reduced, Midrange, and Preserved Ejection Fraction
Authors: Djordjevic Tea , Arena Ross , Guazzi Marco , Popovic Dejana
Published: September 2020

Background:

Ischemic heart disease is a leading cause of heart failure (HF), which continues to carry a high mortality despite considerable improvements in diagnosis and treatment. N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) measured at rest is a recognized diagnostic and prognostic marker of HF of reduced ejection fraction (HFrEF); however, its value in patients with HF of midranged/preserved ejection fraction (HFmrEF/HFpEF) is not well established. We examined the prognostic value of NT-pro-BNP during recovery from exercise in patients with ischemic HF (IHF) of any ejection fraction.

Methods:

Patients (n = 213) with HF (123 HFrEF, 90 HFmrEF/HFpEF) underwent cardiopulmonary exercise testing. Doppler echocardiography was used to estimate resting pulmonary artery systolic pressure (PASP) and tricuspid annular plane systolic excursion (TAPSE). NT-pro-BNP was determined at rest, peak exercise, and after 1 min of exercise recovery.

Results:

Patients with HFrEF had higher plasma levels of NT-pro-BNP at rest, peak exercise, and recovery than those with HFmrEF/HFpEF (984 ± 865 vs 780 ± 805; 1012 ± 956 vs 845 ± 895; 990 ± 1013 vs 808 ± 884 pg/mL; P < .01, respectively), whereas ΔNT-pro-BNP peak/rest and ΔNT-pro-BNP recovery/peak were similar (60 ± 100 vs 50 ± 96; −25 ± 38 vs −20 ± 41 pg/mL, P > .05). During the tracking period (22.4 ± 20.3 mo), 34 patients died, 2 underwent cardiac transplantation, and 3 had left ventricular assist device implantation. In a multivariate regression model, only NT-pro-BNP during exercise recovery and TAPSE/PASP were retained in the regression for the prediction of adverse events (χ2 = 11.4, P <.001).

Conclusions:

NT-pro-BNP value during exercise recovery may be a robust predictor of adverse events in patients with IHF across a wide range of ejection fraction.
Identification of Patients With COPD in a Cardiac Rehabilitation Setting
Authors: Ozemek Cemal , Arena Ross , Rouleau Codie R. , Campbell Tavis S. , Hauer Trina , Wilton Stephen B. , Stone James , Laddu Deepika , Williamson Tamara M. , Liu Hongwei , Austford Leslie D. , Roman Michael A. , Aggarwal Sandeep
Published: September 2020

Purpose:

To examine the feasibility of screening for chronic obstructive pulmonary disease (COPD) in an outpatient cardiac rehabilitation (CR) setting and to evaluate the detection rate of COPD using a targeted screening protocol.

Methods:

A total of 95 patients (62.5 ± 10.0 yr; men, n = 77), >40-yr old with a history of smoking were included in the study sample. Each participant answered the 5-item Canadian Lung Health Test (CLHT) questionnaire assessing symptoms such as coughing, phlegm, wheezing, shortness of breath, and frequent colds. Endorsing ≥1 item was indicative of potential COPD and warranted pulmonary function testing (PFT) and/or spirometry to diagnose or rule out COPD.

Results:

The CLHT questionnaire identified 44 patients at risk for COPD, with an average of 1.9 ± 1.2 items endorsed. Of the patients who underwent PFT, 6 new cases of mild COPD were diagnosed, resulting in a true positive rate with CLHT screening of 19% and a false-positive rate of 81%.

Conclusions:

Implementing the CLHT to patients referred to CR correctly identified COPD in <20% of cases. Using the CLHT to screen for COPD prior to starting CR may not be optimal, due to disparities between true- and false-positive rates.
Differences in Comorbid Conditions Among Older Adult Participants in Cardiac Rehabilitation
Authors: Cahill Benjamin J. , Allsup Kelly , Delligatti Amanda , Althouse Andrew D. , Forman Daniel E.
Published: September 2020

Purpose:

Most older adults eligible for cardiac rehabilitation (CR) do not participate or participate with low frequency, although it is a standard of care for patients with cardiovascular disease (CVD). Identifying the barriers to older adult participation is key in improving CR efficacy.

Methods:

A range of patient characteristics was analyzed in relation to on-site frequency of participation in a CR program by older adult patients. These characteristics included demographics and indications for referral, as well as CVD and non-CVD diagnoses. The prevalence of these characteristics was compared among three patient cohorts, ranging from high contact frequency to minimal contact frequency of on-site participation in CR.

Results:

Among the three participation frequency cohorts, no differences were noted in demographic factors, indications for referral, or CVD diagnoses. However, patients with hearing impairment (OR = 4.15: 95% CI, 1.32-13.08) or visual impairment (OR = 4.11: 95% CI, 1.46-11.59) at time of enrollment were more likely to be found in the minimal contact cohorts than the moderate or high contact frequency cohorts.

Conclusions:

Whereas differences in CVD had little bearing on frequency of CR participation in older patients, differences in hearing and visual impairment varied significantly. Patients with hearing and vision impairments attended less frequently. Sensory impairment has previously been demonstrated to impact health care utilization by older adults, but is rarely considered in the treatment of CVD or CR. As sensory impairments are extremely prevalent among geriatric patients, further study of these potential barriers to care might open possibilities for older adult participation in CR.
New Surgical Approach for Secondary Intraocular Lens Implantation Using an Artificial Bag with Optic Capture in Patients with Intraocular Lens Dislocation
Authors: Yoo Woong-Sun , Cho Yong-Wun , Park Mi-Hwa , Kang Hyun-Ji , Kim Seong-Jae
Published: September 2020

Purpose:

We present a newly developed approach to secondary intraocular lens (IOL) implantation, which uses an artificial bag with optic capture (i.e., ABC technique) in patients with IOL dislocation.

Methods:

This is a retrospective, noncomparative, and interventional case series that reveals the results of secondary IOL implantation using an artificial bag with optic capture in four cases of IOL dislocation. All patients underwent the abovementioned surgery and were followed up for at least 6 months.

Results:

The best-corrected visual acuity of patients ranged from 20/30 to 20/20. The IOL of all patients showed no tilting or decentration with normal intraocular pressure.

Conclusion:

We believe that this method produces satisfactory results and will be especially beneficial to retinal surgeons for the management of patients with IOL dislocation.
Eye Banking: One Cornea for Multiple Recipients
Authors: Gadhvi Kunal A. , Coco Giulia , Pagano Luca , Kaye Stephen B. , Ferrari Stefano , Levis Hannah J. , Parekh Mohit , Romano Vito
Published: September 2020

Purpose:

Corneal transplantation is the most frequently performed transplant procedure. In much of the world, the demand for donor tissue heavily outstrips supply. With developments within lamellar corneal graft surgery, the use of split corneal donor tissue to increase donor tissue supply seems a pragmatic solution to reduce the supply and demand mismatch. This is especially important with tissue supply expected to be affected by the COVID-19 pandemic.

Methods:

A literature review of techniques was performed, enabling multiple transplants to be derived from a single donor and simulation of a model to quantify the number of corneas potentially saved.

Results:

Studies on splitting corneal donor tissue have demonstrated that up to 5 recipients may benefit from 1 donor scleral button. The impact of splitting donor tissue may provide a saving of up to 25.3% of donor graft tissue.

Conclusions:

Splitting and preparing the donor tissue within an eye bank will improve tissue validation and donor tissue availability and may increase surgeon efficiency.
Do Patients With Keratoconus Have Minimal Disease Knowledge?
Authors: Baenninger Philipp B. , Bachmann Lucas M. , Ritzmann Markus , Blaser Frank , Gatzioufas Zisis , Alder Marco , Handzic Armin , Iselin Katja , Kaufmann Claude , Thiel Michael A.
Published: September 2020

Purpose:

To assess whether Swiss adult citizens diagnosed with keratoconus have the minimal knowledge that a corneal specialist would expect they should have.

Methods:

Experts defined the “minimal keratoconus knowledge” (MKK) with respect to definition, risk factors, symptoms, and possible treatment options of keratoconus. A survey was performed in 167 patients with keratoconus [mean age 38.8 years (SD 13.9), 77.7% male] in 5 specialized institutions. Of each participant, salient clinical characteristics, highest educational level, paramedical background, and specific health experience with keratoconus in the social surrounding were obtained. We calculated the proportion of MKK and examined whether patients with higher education and greater disease experience would perform better than those from other groups in multivariate analyses.

Results:

No single citizen reached 100% MKK. The mean MKK was 35.2%, and the range was 0% to 76.2%. Participants with a university degree had only a moderately higher MKK [+8.7% (95% confidence interval: 4.4–13.0); P < 0.001]. Per age decile, the MKK declined by 3.1% (95% confidence interval: 1.2–4.9), P = 0.002. Disease duration, severity of keratoconus in Kmax values, and history of surgical treatment did not significantly increase MKK. Surprisingly, MKK was also lower in patients with a paramedical background [−6.3% (−14.1 to 1.4); P = 0.107].

Conclusions:

This sample of Swiss patients with keratoconus did not know more than a third of the MKK. We found a little difference within various subgroups. There is a substantial mismatch between caregivers' expectations of patients' knowledge and patients' active knowledge regarding their condition. This may lead to an inefficient care delivery and misunderstandings.
Descemet Stripping Endothelial Keratoplasty Outcomes in Patients With Rheumatoid Arthritis
Authors: Cinar Yasin , Delvadia Bela , Sahin Alparslan , Hammersmith Kristin M. , Nagra Parveen K. , Rapuano Christopher J. , Syed Zeba A.
Published: September 2020

Purpose:

To review the graft and visual outcomes in a series of patients with rheumatoid arthritis (RA) who underwent Descemet stripping endothelial keratoplasty (DSEK).

Methods:

In this case series, the electronic medical records at Wills Eye Hospital were queried for cases of patients with RA who underwent DSEK between January 1, 2009 and September 1, 2018. Charts were reviewed to obtain demographic data, medical history, ocular history, surgical variables, graft survival, and visual acuity outcomes.

Results:

During the study period, 22 transplants performed in 18 eyes of 15 patients with RA were eligible for inclusion. The mean age at the time of initial DSEK was 70.5 ± 11.1 years (range 46–87). The mean follow-up time for the included eyes was 4.89 ± 2.71 years (range 1.95–10.39). The overall estimated graft survival was 8.26 ± 0.81 years with a 5-year survival rate of 88.9%. A significant improvement from preoperative best corrected visual acuity (logarithm of the minimum angle of resolution 0.84, approximately 20/140) to the most recent follow-up (logarithm of the minimum angle of resolution 0.29, approximately 20/40) was noted (P < 0.001).

Conclusions:

In our case series, patients with a history of RA underwent successful DSEK with excellent graft survival rates and visual acuity outcomes. Well-controlled RA should therefore not be considered a deterrent to performing DSEK.
Descemet Membrane Endothelial Keratoplasty in Children
Authors: Pereira Nicolas Cesário , Pereira Gomes José Álvaro , Tonin Camile , Verardo Fabiana Orondjian , Felippe Rodolpho Sueiro , dos Santos Forseto Adriana
Published: September 2020

Purpose:

To describe the outcomes of Descemet membrane endothelial keratoplasty (DMEK) performed in amblyopic aged (younger than 8 years) children.

Methods:

This is a single-center retrospective study, including 11 eyes (7 congenital hereditary endothelial dystrophy and 4 congenital glaucoma) of 6 children in amblyopic age undergoing DMEK by a single surgeon (N.C.P.) at Sorocaba Eye Hospital from December 2015 to November 2017. Best spectacle-corrected visual acuity, biomicroscopy, pachymetry, endothelial cell density, and complications were evaluated.

Results:

No intraoperative complications occurred. Graft detachment occurred in 1 eye (9.1%) and was successfully managed with rebubbling. No primary graft failure or pupillary block was observed. All pachymetric measurements improved, and the corneal edema clinically resolved in all eyes within 2 weeks after the procedure. At the last follow-up (mean 30 months), best spectacle-corrected visual acuity was ≥20/40 in 7 (77.8%) of 9 eyes from patients cooperative enough to assess vision. All children began visual stimulation therapy and amblyopic treatment within 1 month of surgery, and all grafts remained clear until the last follow-up. The mean preoperative donor endothelial cell density was 2588 ± 236 cells/mm2, which decreased to 1726 ± 292 cells/mm2 2 years after surgery, yielding a 33% reduction (P < 0.001). No immunologic graft reaction, secondary graft failure, or cataracts were observed during the follow-up period.

Conclusions:

In this series, DMEK was performed to successfully treat endothelial dysfunction in children. However, the procedure is more challenging, and more studies with more patients and longer follow-up are needed to confirm the superiority of DMEK in treating endothelial dysfunction in children.
Potential hypotensive effects of Umezu polyphenols: a 14-week community-based, double-masked and placebo-controlled trial
Authors: Takemura Shigeki , Yoshimasu Kouichi , Tsuno Kanami , Kuroda Mototsugu , Kishida Kunihiro , Mitani Takahiko , Miyashita Kazuhisa
Published: September 2020

Objective

To evaluate blood pressure (BP)-lowering effects of Umezu polyphenols, polyphenols contained in Japanese plums, in a community-based sample by double-masked and placebo-controlled design.

Methods

Seventy-two Japanese community-dwellers who were interested in prevention or control of their BP (preferably high-normal BP or grade I hypertension) but without antihypertensive medication were randomized into Umezu polyphenols or placebo groups. Each subject took 800 mg/day of Umezu polyphenols or placebo for 12 weeks, followed by a 2-week washout period. Their home and office BP were monitored for 14 weeks in a double-masked manner. We analyzed 56 subjects who met the inclusion criteria.

Results

Home BP increased gradually in both the groups during the intervention period, while diastolic office BP insignificantly decreased in the intervention group. During the washout period, home systolic BP in the morning elevated only in the intervention group.

Conclusions

The study failed to collect consistent evidence of a clear persistent hypotensive effect of Umezu polyphenols.
The Effects of Market Competition on Cardiologists’ Adoption of Transcatheter Aortic Valve Replacement
Authors: Groeneveld Peter W. , Yang Lin , Segal Andrea G. , Karaca-Mandic Pinar , Kanter Genevieve P.
Published: September 2020

Background:

For decades, the prevailing assumption regarding the diffusion of high-cost medical technologies has been that competitive markets favor more aggressive adoption of new treatments by health care providers (ie, the “Medical Arms Race”). However, novel regulations governing the adoption of transcatheter aortic valve replacement (TAVR) may have disrupted this paradigm when TAVR was introduced.

Objective:

The objective of this study was to assess the relationship between the market concentration of physician group practices and the adoption of TAVR in its first years of use.

Research Design:

This was a retrospective cohort study.

Subjects:

Physician group practices (n=5116) providing interventional cardiology services in the United States from May 1, 2012, to December 31, 2014.

Measures:

The first use of TAVR as indicated by a fee-for-service Medicare claim. Covariates including characteristics of the physician groups (ie, case volume, hospital affiliation, mean patient risk) as well as county-level and market-level characteristics.

Results:

By the close of 2014, 9.3% of practices had adopted TAVR. Cox proportional hazards models revealed a hazard ratio of 1.26 (95% confidence interval: 1.16–1.37, P<0.001) per 1000 point increase in the physician group practice Herfindahl-Hirschman Index, indicating each 1000 point increase in group practice Herfindahl-Hirschman Index was associated with a 26% relative increase in the rate of TAVR adoption.

Conclusions:

Adoption of TAVR by physician groups in concentrated markets was potentially a consequence of the unique regulations governing TAVR reimbursement, which favored the adoption of TAVR by physician groups with greater market power. These findings have important implications for how future regulations may shape patterns of technology adoption.
The Effects of a Stress Management Group Education Program on Symptoms of Depression, Anxiety, and Stress in People With Comorbid Diabetes and Chronic and/or Recurrent Foot and Ankle Complications
Authors: Lu Annie D. , Bonder-Smith Sheila , Li Xiaochun
Published: September 2020

BACKGROUND:

Individuals with diabetic foot and ankle complications are at heightened risk for depression, anxiety, and stress.

PURPOSE:

This study evaluated the effect of a stress management group education (SMGE) program in this population.

METHODS:

The 21-question Depression Anxiety Stress Scales and the Problem Areas in Diabetes scale were administered prior to, upon completion of, and at approximately 6 weeks after the program.

RESULTS:

Twenty-five patients from an urban diabetic foot and ankle center completed the study.

CONCLUSION:

The SMGE program demonstrated decreased levels of anxiety, depression, and diabetes problem areas for our study population.