bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clusterin as a serum biomarker candidate contributes to the lung fibroblasts activation in chronic obstructive pulmonary disease
Authors: Zhang Qiang , Yue Yuanyi , Zheng Rui 
Published: February 2022

Abstract

Background:
Fibrosis in the peripheral airways contributes to airflow limitation in patients with chronic obstructive pulmonary disease (COPD). However, the key proteins involved in its development are still poorly understood. Thus, we aimed to identify the differentially expressed proteins (DEPs) between smoker patients with and without COPD and elucidate the molecular mechanisms involved by investigating the effects of the identified biomarker candidate on lung fibroblasts.

Methods:
The potential DEPs were identified by isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. The messenger RNA and protein levels of clusterin (CLU) in COPD patients and 12% cigarette smoke extract (CSE)-treated human bronchial epithelial cells were determined at the indicated time points. Furthermore, an in vitro COPD model was established via the administration of 8% CSE to normal human lung fibroblasts (NHLFs) at indicated time points. The effects of CSE treatment and CLU silencing on proliferation and activation of lung fibroblasts were analyzed.

Results:
A total of 144 DEPs were identified between COPD patients and normal smokers. The iTRAQ-based proteomics and bioinformatics analyses identified CLU as a serum biomarker candidate. We also discovered that CLU levels were significantly increased (P
< 0.0001) in Global Initiative for Obstructive Lung Disease II, III, and IV patients and correlated (P
< 0.0001) with forced expiratory volume in 1 s (R = −0.7705), residual volume (RV) (R = 0.6281), RV/total lung capacity (R = 0.5454), and computerized tomography emphysema (R = 0.7878). Similarly, CLU levels were significantly increased in CSE-treated cells at indicated time points (P < 0.0001). The CSE treatment significantly inhibited the proliferation, promoted the inflammatory response, differentiation of NHLFs, and collagen matrix deposition, and induced the apoptosis of NHLFs; however, these effects were partially reversed by CLU silencing.

Conclusion:
Our findings suggest that CLU may play significant roles during airway fibrosis in COPD by regulating lung fibroblast activation.
Effect on surgery outcomes owing to the interval between onset of symptoms and surgery of patients with acute type A aortic dissection
Authors: Li Shouming , Wei Duoliang , Wang Zhenhua , Song Han , Cheng Shaopeng , Zhao Xin 
Published: February 2022

Abstract

Background:
This study aimed to identify whether the interval from onset of symptoms to surgery affects the outcomes of surgery in patients with acute type A aortic dissection (AAAD).

Methods:
This study retrospectively examined 249 patients with AAAD who underwent Sun's procedure. All patients were divided into 2 groups, hyperacute and acute, according to the interval from onset of symptoms to surgery. The primary endpoint was all-cause early mortality, and the secondary endpoint was early reoperation.

Results:
The surgery time, cardiopulmonary bypass time, clamp time, and selective cerebral perfusion time were not significantly different between the 2 groups. The intensive care unit length of stay and duration of mechanical ventilation of the 2 groups were 185.50 hours versus 185.00 hours (P = 0.970) and 41.50 hours versus 44.00 hours (P = 0.678), respectively. There were 52 early deaths: 29 in the hyperacute group and 23 in the acute group (21.6% vs. 20.0%, P = 0.751). The incidence of reoperation was 0.7% and 0.9% (P > 0.999), respectively. The incidence rates of postoperative acute heart failure (AHF), acute respiratory failure (ARF), nervous dysfunction, and acute kidney injury were 37.3% versus 25.2% (P = 0.041), 51.5% versus 51.3% (P = 0.976), 13.4% versus 7.0% (P = 0.096), and 37.3% versus 37.4% (P = 0.990), respectively. Multivariable analysis indicated that surgery in the hyperacute phase might be an independent risk factor for AHF (OR: 1.765; 95% CI: 1.021–3.052; P = 0.042).

Conclusion:
Surgery in the hyperacute phase of AAAD was associated with postoperative AHF. Therefore, early medical management or interventional therapy for complications before surgery performed by experienced surgeons is recommended, especially in the hyperacute phase.
24-hour Perfusion of Porcine Myocutaneous Flaps Mitigates Reperfusion Injury: A 7-day Follow-up Study
Authors: Brouwers Kaj , Thijssen Max F. , Kruit Anne Sophie , van Midden Dominique , Koers Erik J. , Zegers Her J.H. , Hummelink Stefan , Ulrich Dietmar J.O. 
Published: February 2022

Background:
Static cold storage is the gold standard of preservation in vascularized composite allotransplantation and allows a preservation time of 4–6 hours. Machine preservation is a promising technique for prolonged preservation; however, studies on extended preservation that compare different preservatives are scarce. This study aims to assess the feasibility of 24-hour acellular perfusion and compares different preservation solutions in a porcine myocutaneous flap replantation model.

Methods:
Six harvested bilateral myocutaneous flaps of three Dutch Landrace pigs were perfused hypothermically for 24 hours with University of Wisconsin machine perfusion solution (UW-MPS; n = 2) or histidine-tryptophan-ketoglutarate solution (HTK; n = 2) or preserved on ice for 4 hours (n = 2) before orthotopic replantation. Animals were observed for 7 days after replantation. Skeletal muscle injury was assessed by biochemical markers during perfusion, and muscle biopsies were analyzed for ischemia reperfusion injury directly after preservation and at 1, 3, and 7 days after replantation.

Results:
Markers of muscle damage varied during perfusion, but decreased overall in both perfusion groups. Flap weight increased 60% and 97% in the HTK-perfused flaps, compared with -6% and -7% in the UW-MPS-perfused flaps after 24 hours. Histopathologic evaluation demonstrated decreased muscle damage in flaps perfused with HTK compared with the UW-MPS-perfused flaps at 1 week after replantation.

Conclusions:
Machine perfusion of myocutaneous flaps for 24 hours with subsequent replantation is feasible, but warrants further research. Perfusion with HTK solution seemed to result in better histological outcomes 7 days after reperfusion compared with UW-MPS.
Polymeric Drug Delivery Devices: Role in Cornea and External Disease
Authors: Roy Aravind , Krishna Venuganti Venkata V. , Chauhan Shreya S. , Garg Prashant 
Published: February 2022

Abstract:The field of ophthalmic drug delivery is undergoing rapid changes not only in the evolution of pharmacologic agents but also in the novel drug delivery vehicles. The ocular surface has limitations to drug penetration because of the presence of tight junctions between basal epithelial cells, which limits the amount of drug that can be absorbed after topical instillation. In addition, nasolacrimal drainage reduces the precorneal residence time significantly. Contact lenses (CLs) have been considered as possible carriers for topical medications because they reside on the ocular surface for a sufficient length of time, and pharmacologic agents may be copolymerized with hydrogels allowing controlled drug diffusion. This strategy reduces the frequency of dosage while improving compliance. Modification of drug delivery vehicles is essential to allow sustained release of the drug from a polymeric complex, facilitate stability and residence time of the drug on the precorneal tear film, and improve penetration into biologic membranes. This review focuses on updates in CL-based and non-CL–based strategies in ophthalmic drug delivery.
Management of Keratoconus With Corneal Rigid Gas-Permeable Contact Lenses
Authors: Itoi Motozumi , Itoi Motohiro 
Published: February 2022

Abstract:
Vision correction using a corneal rigid gas-permeable contact lens, which is relatively safe, easy to replace, and economical, is still the basis of the management for keratoconus. For eyes with keratoconus, two fitting strategies have traditionally been used in Japan: apical touch fitting with spherical lenses and parallel fitting with multicurve lenses. These two techniques have different success rates depending on the type and severity of keratoconus. Therefore, it is important to classify eyes with keratoconus into four types according to the shape of the cornea and select the prescription techniques according to this classification. If the corneal GPs prescribed by these fitting methods cannot be used because of mechanical irritation to the corneal epithelium, the “piggyback lens system” is an effective option. Furthermore, proper lens care must be instructed to patients to prevent contact lens-related complications and maintain visual function. If these fittings and introductions can be performed properly, corneal GPs can safely provide effective and comfortable vision for many patients with keratoconus, even for those with severe keratoconus.
Posterior Ankle Impingement Syndrome Clinical Features Are Not Associated With Imaging Findings in Elite Ballet Dancers and Athletes
Authors: Baillie Peta , Ferrar Katia , Cook Jill , Smith Peter , Lam Jason , Mayes Susan 
Published: February 2022

Objective:
To assess the association between clinical features and magnetic resonance imaging (MRI) findings in posterior ankle impingement syndrome (PAIS) and to compare the prevalence of imaging findings between participants with and without a clinical diagnosis of PAIS.

Design:
Case-control study.

Setting:
Elite ballet and sport.

Participants:
Eighty-two male (54%) and female participants comprising ballet dancers (n = 43), cricket fast bowlers (n = 24), and football (soccer) players (n = 15).

Independent Variables:
Clinical: posterior ankle pain on body chart, passive plantarflexion pain provocation test. Patient-reported outcome measures: Oslo Sports Trauma Research Center Overuse Injury Questionnaire, Foot and Ankle Ability Measure Sports subscale.

Main Outcome Measures:
Imaging findings including posterior ankle bone marrow edema, os trigonum (± bone marrow edema, and increased signal at synchondrosis), Stieda process (± bone marrow edema), talocrural and subtalar joint effusion–synovitis size, flexor hallucis longus tendinopathy, and tenosynovitis identified as present or absent on 3.0-Tesla MRI.

Results:
Imaging findings were not associated with posterior ankle pain or a positive ankle plantarflexion pain provocation test. Imaging findings were not associated with patient-reported outcome measures. Imaging findings did not differ between PAIS-positive and PAIS-negative groups. Os trigonum and Stieda process were prevalent despite clinical status.

Conclusions:
The lack of association between imaging findings and clinical features questions the role of imaging in PAIS. Clinicians should rely primarily on clinical assessment in the diagnosis and management of patients with PAIS.
Performance and long-term consistency of five Galliform 68Ge/68Ga generators used for clinical Ga-68 preparations over a 4 year period
Authors: Sammartano Antonino , Migliari Silvia , Scarlattei Maura , Baldari Giorgio , Serreli Giulio , Lazzara Chiara , Garau Ludovico , Ghetti Caterina , Ruffini Livia 
Published: February 2022

Background
Gallium-68 is a positron emitter for PET applications that can be produced without cyclotron by a germanium (Ge-68) chloride/gallium (Ga-68) chloride generator. Short half-life (67.71 min) of Ga-68, matching pharmacokinetic properties of small biomolecules, facilitates isotope utilization in compounding radiopharmaceuticals for PET imaging. The increasing cost of good manufacturing practice-compliant generators has strengthened the need for radionuclide efficient use by planning specific radiopharmaceutical sessions during the week, careful maintenance of the generator and achievement of high labeling yield and radiochemical purity (RCP) of the radiolabeled molecules.

Methods
The aim of this study was to evaluate the annual performance of five consecutive 68Ge/68Ga generators used for small-scale preparations of 68Ga-radiopharmaceuticals. To assess the long-term efficiency of isotope production we measured the weekly elution yield. To assess process efficiency we measured elution yield, labeling yield and RCP of four radiopharmaceutical preparations (68Ga-DOTATOC, 68Ga-PSMA-HBED-CC, 68Ga-PENTIXAFOR and 68Ga-DOTATATE).

Results
The annual mean elution yield of the generators was 74.7%, higher than that indicated by the manufacturer, and it never went below 65%. The Ge-68 level in the final products was under the detection limits in all the produced batches (mean value 0.0000048%). The RCP of radiopharmaceuticals determined by high-performance liquid chromatography was 98 ± 0.22%. The mean yield of radiolabelling was 64.68, 68.71, 57 and 63.68% for 68Ga-DOTATOC, 68Ga-PSMA-HBED-CC, 68GaPENTIXAFOR and 68Ga-DOTATATE.

Conclusion
The ability to prepare in the hospital radiopharmacy high-purity and pharmaceutically acceptable 68Ga-radiolabeled probes on a routine basis facilitates patient access to precision imaging for clinical and research aims.
Perianal Crohn Disease Is More Common in Children and Is Associated With Complicated Disease Course Despite Higher Utilization of Biologics
Authors: Atia Ohad , Focht Gili , Lujan Rona , Ledder Oren , Greenfeld Shira , Kariv Revital , Dotan Iris , Yanai Henit , Gabay Hagit , Balicer Ran , Haklai Ziona , Nevo Daniel , Turner Dan 
Published: February 2022

ABSTRACTBackground and Objectives:Both perianal and pediatric‐onset Crohn disease (CD) disease are associated with complicated disease course and higher drug utilization. we aimed to explore the differences between pediatric and adult‐onset perianal CD and their disease course.Methods:We included all patients with newly diagnosed CD from 2005 to 2019 at two Israeli Health Maintenance Organizations, covering 78% of the population. A combination of ICD‐9 codes, radiology and procedures was used to define fistulizing perianal CD (PCD) and its severity according to the association with simple and complex perianal disease.Results:A total of 12,905 patients were included (2186 [17%] pediatric‐onset, 10,719 [83%] adults), with a median follow‐up of 7.8 years. PCD was diagnosed in 1530 (12%) patients, with higher incidence in children (308 [14%] children vs 1222 adults [11%]; P < 0.001). Children had higher incidence of severe PCD (141/308 [47%] vs 433/1222 [35%]; P < 0.001). At 5 years, children with PCD were more likely than adults to be treated with biologics (212 [69%] vs 515 [42%]; odds ratio [OR] 2.6 [95% confidence interval (CI) 1.6–4.0]; P < 0.001) and immunomodulators (238 [74%] vs 643 [53%]; OR 2.8 [95% CI 2.1–3.6]; P < 0.001). PCD in children was still associated with poorer disease outcomes as shown for surgeries (36 [12%] vs 93 [8%]; P = 0.02) and steroid‐dependency (52 [17%] vs 156 [13%]; P < 0.001). Multivariable modeling indicated that the severity of PCD is a stronger predictor of disease course than age.Conclusion:PCD is more common in pediatric‐onset CD and is associated with higher drug utilization and worse disease outcomes, in large due to higher rate of severe PCD in children.
Spanish National Registry of Paediatric Coeliac Disease
Authors: Pérez Solís David , Cilleruelo Pascual Ma Luz , Ochoa Sangrador Carlos , García Burriel Jose Ignacio , Sánchez‐Valverde Visus Félix , Eizaguirre Arocena Francisco Javier , Garcia Calatayud Salvador , Martinez‐Ojinaga Nodal Eva , Donat Aliaga Ester , Barrio Torres Josefa , Castillejo de Villasante Gemma , Miranda Cid Ma del Carmen , Torres Peral Ricardo , Vecino Lopez Raquel , Juste Ruiz Mercedes , Armas Ramos Honorio , Barros Garcia Patricia , Leis Trabazo Rosaura , Solaguren Alberdi Rosa , Salazar Quero José Carlos , Garcia Romero Ruth , Ortigosa del Clastillo Luis , Peña Quintana Luis , Urruzuno Telleria Pedro , Codoñer Franch Pilar , Garcia Casales Zuriñe , Masiques Mas Maria Lluïsa , Galicia Poblet Gonzalo , Martinez Costa Cecilia , Balmaseda Serrano Elena , Polanco Allué Isabel , Ribes Koninck Carmen , Román Riechmann Enriqueta ,   Coeliac Disease Working Group of the Spanish Gastroenterology, Hepatology, Paediatric Nutrition Society (SEGHNP)
Published: February 2022

ABSTRACTObjectives:Over the last several decades, there has been a tendency towards a predominance of less symptomatic forms of coeliac disease (CD) and an increase in the patient age at diagnosis. This study aimed to assess the clinical presentation and diagnostic process of paediatric CD in Spain.Methods:A nationwide prospective, observational, multicentre registry of new paediatric CD cases was conducted from January 2011 to June 2017. The data regarding demographic variables, type of birth, breast‐feeding history, family history of CD, symptoms, height and weight, associated conditions, serological markers, human leukocyte antigen (HLA) phenotype, and histopathological findings were collected.Results:In total, 4838 cases (61% girls) from 73 centres were registered. The median age at diagnosis was 4 years. Gastrointestinal symptoms were detected in 71.4% of the patients, and diarrhoea was the most frequent symptom (45.9%). The most common clinical presentation was the classical form (65.1%) whereas 9.8% ofthe patients were asymptomatic. There was a trend towards an increase in the age at diagnosis, proportion of asymptomatic CD cases, and usage of anti‐deamidated gliadin peptide antibodies and HLA typing for CD diagnosis. There was, however, a decreasing trend in the proportion of patients undergoing biopsies. Some of these significant trend changes may reflect the effects of the 2012 ESPGHAN diagnosis guidelines.Conclusions:Paediatric CD in Spain is evolving in the same direction as in the rest of Europe, although classical CD remains the most common presentation form, and the age at diagnosis remains relatively low.
Preload Dependence Fails to Predict Hemodynamic Instability During a Fluid Removal Challenge in Children*
Authors: Jacquet-Lagrèze Matthias , Acker Amélie , Hentzen Julie , Didier Capucine , De Lamer Sabine , Chardonnal Laurent , Bouhamri Noureddine , Portran Philippe , Schweizer Rémi , Lilot Marc , Fellahi Jean-Luc 
Published: February 2022

OBJECTIVES:
Fluid overload increases morbidity and mortality in PICU patients. Active fluid removal improves the prognosis but may worsen organ dysfunction. Preload dependence in adults does predict hemodynamic instability induced by a fluid removal challenge (FRC). We sought to investigate the diagnostic accuracy of dynamic and static markers of preload in predicting hemodynamic instability and reduction of stroke volume during an FRC in children. We followed the Standards for Reporting of Diagnostic Accuracy statement to design conduct and report this study.

DESIGN:
Prospective noninterventional cohort study.

SETTINGS:
From June 2017 to April 2019 in a pediatric cardiac ICU in a tertiary hospital.

PATIENTS:
Patients 8 years old or younger, with symptoms of fluid overload after cardiac surgery, were studied.

INTERVENTIONS:
We confirmed preload dependence by echocardiography before and during a calibrated abdominal compression test. We then performed a challenge to remove 10-mL/kg fluid in less than 120 minutes with an infusion of diuretics. Hemodynamic instability was defined as a decrease of 10% of mean arterial pressure.

MEASUREMENT AND MAIN RESULTS:
We compared patients showing hemodynamic instability with patients remaining stable, and we built receiver operative characteristic (ROC) curves. Among 58 patients studied, 10 showed hemodynamic instability. The area under the ROC curve was 0.55 for the preload dependence test (95% CI, 0.34–0.75). Using a threshold of 10% increase in stroke volume index (SVi) during calibrated abdominal compression, the specificity was 0.30 (95% CI, 0.00–0.60) and the sensitivity was 0.77 (95% CI, 0.65–0.88). Mean arterial pressure variation and SVi variation were not correlated during fluid removal; r = 0.19; 95% CI –0.07 to 0.43; p = 0.139.

CONCLUSIONS:
Preload dependence is not accurate to predict hemodynamic instability during an FRC. Our data do not support a reduction in intravascular volume being mainly responsible for the reduction in arterial pressure during an FRC in children.
Racial and Ethnic Differences in Inpatient Palliative Care for Pediatric Stem Cell Transplant Patients*
Authors: McKee Maya N. , Palama Brett K. , Hall Matt , LaBelle James L. , Bohr Nicole L. , Hoehn K. Sarah 
Published: February 2022

OBJECTIVES:
Racial/ethnic disparities in utilizing inpatient palliative care services are well documented in the adult literature. However, the impact of racial/ethnic disparities in the context of pediatric palliative care is less well understood even in high-acuity patient populations such as stem cell transplant patients. We investigated racial/ethnic differences in the utilization of inpatient palliative care consultations (IPCCs) for pediatric stem cell transplant patients.

STUDY DESIGN:
A retrospective cohort study was conducted using the Pediatric Health Information System database. A generalized linear mixed effects model was developed to assess demographic and clinical characteristics associated with the likelihood of receiving IPCC.

SETTING:
Thirty-eight tertiary pediatric hospitals in the United States.

PATIENTS:
Pediatric patients undergoing stem cell transplantation for any indication from January 2017 to December 2019.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Of the 1,193 inpatient encounters studied, 12% (n = 143) included a palliative care consult. IPCC rates varied across hospitals with a median rate of 5.97% (interquartile range, 0.00–20.71). In multivariable analyses, Hispanic/Latinx patients were 59% less likely to receive IPCC compared with non-Hispanic White patients (odds ratio [OR], 0.41; 95% CI, 0.21–0.78). This difference persisted after adjusting for all other sociodemographic and clinical factors. In terms of the other clinical characteristics, having a malignant condition and mechanical ventilation were associated with significantly increased odds of receiving IPCC for the entire cohort (OR Malignancy: 1.93; 95% CI: 1.07-3.51; OR Mechanical Ventilation: 2.37; 95% CI: 1.36-4.13). The remainder of the variables were not found to be significantly associated with IPCC.

CONCLUSIONS:
Racial and ethnic differences exist in the likelihood of receiving palliative care consultations among hospitalized pediatric stem cell transplant recipients. Evaluating the impact of systemic racism and social determinants on palliative care medicine as well as standardizing early integration of IPCC may potentially mitigate disparities in this population.