bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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.
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

ABSTRACT:

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.
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.