bluuebunny/crossref_metadata_2025 huggingface dataset:
Capnographic monitoring reduces hypoxia incidence in older patients undergoing gastrointestinal endoscopy under propofol sedation: study protocol for a multicenter randomized controlled trial
Authors: Lian Qiuyue , Chen Shaoyi , Cheng Xiangyang , Zhang Jie , Yu Weifeng , Zhou Renlong , Su Diansan
Published: March 2023

Background

Hypoxia is a very common adverse event that occurs during gastrointestinal endoscopy under sedation, especially in older patients, owing to limited reservation of heart, brain, lung, and other organs. Prolonged or severe hypoxia can cause ischemia of the coronary artery and permanent nervous system damage, and even result in death. Hence, it is imperative to reduce or prevent hypoxia during gastrointestinal endoscopy under sedation in older patients. Although several oxygen delivery methods would reduce hypoxia during this procedure, early detection of respiratory depression and early administration of intervention would be the best method to reduce or even confirm the hypoxia. Capnographic monitoring is reportedly more sensitive for detecting respiratory depression before the onset of hypoxia than the current clinical routine monitoring of pulse oxygen saturation; however, its effect is controversial. Therefore, in this study, we aimed to improve the safety of gastrointestinal endoscopy under sedation in older patients.

Methods

A multicenter, randomized, single-blind, two-arm parallel-group, controlled with an active comparator, interventional superiority clinical trial will be conducted to evaluate the impact of an additional capnographic monitoring-based intervention on the incidence of hypoxia in older patients. Patients (n = 1800) scheduled for gastrointestinal endoscopy with propofol sedation will be randomly assigned to either a control or interventional arm, wherein standard or capnographic monitoring is implemented, respectively.

Discussion

This study primarily aims to examine whether an additional capnographic monitoring-based intervention can reduce the incidence of hypoxia in older patients during gastrointestinal endoscopy under propofol and sufentanil sedation. The results of this study may extensively impact gastrointestinal endoscopy under sedation and the development of associated guidelines.

Trial registration

ClinicalTrials.gov NCT05030870. Registered on September 1, 2021.
A randomised study of rituximab and belimumab sequential therapy in PR3 ANCA-associated vasculitis (COMBIVAS): design of the study protocol
Authors: McClure Mark E. , Gopaluni Seerapani , Wason James , Henderson Robert B. , Van Maurik Andre , Savage Caroline C.O. , Pusey Charles D. , Salama Alan D. , Lyons Paul A. , Lee Jacinta , Mynard Kim , Jayne David R. , Jones Rachel B. ,   on behalf the COMBIVAS investigators
Published: March 2023

Background

Sequential B cell-targeted immunotherapy with BAFF antagonism (belimumab) and B cell depletion (rituximab) may enhance B cell targeting in ANCA-associated vasculitis (AAV) through several mechanisms.

Methods

Study design: COMBIVAS is a randomised, double-blind, placebo-controlled trial designed to assess the mechanistic effects of sequential therapy of belimumab and rituximab in patients with active PR3 AAV. The recruitment target is 30 patients who meet the criteria for inclusion in the per-protocol analysis. Thirty-six participants have been randomised to one of the two treatment groups in a 1:1 ratio: either rituximab plus belimumab or rituximab plus placebo (both groups with the same tapering corticosteroid regimen), and recruitment is now closed (final patient enrolled April 2021). For each patient, the trial will last for 2 years comprising a 12-month treatment period followed by a 12-month follow-up period.

Participants: Participants have been recruited from five of seven UK trial sites. Eligibility criteria were age ≥ 18 years and a diagnosis of AAV with active disease (newly diagnosed or relapsing disease), along with a concurrent positive test for PR3 ANCA by ELISA.

Interventions: Rituximab 1000 mg was administered by intravenous infusions on day 8 and day 22. Weekly subcutaneous injections of 200 mg belimumab or placebo were initiated a week before rituximab on day 1 and then weekly through to week 51. All participants received a relatively low prednisolone (20 mg/day) starting dose from day 1 followed by a protocol-specified corticosteroid taper aiming for complete cessation by 3 months.

Outcomes: The primary endpoint of this study is time to PR3 ANCA negativity. Key secondary outcomes include change from baseline in naïve, transitional, memory, plasmablast B cell subsets (by flow cytometry) in the blood at months 3, 12, 18 and 24; time to clinical remission; time to relapse; and incidence of serious adverse events. Exploratory biomarker assessments include assessment of B cell receptor clonality, B cell and T cell functional assays, whole blood transcriptomic analysis and urinary lymphocyte and proteomic analysis. Inguinal lymph node and nasal mucosal biopsies have been performed on a subgroup of patients at baseline and month 3.

Discussion

This experimental medicine study provides a unique opportunity to gain detailed insights into the immunological mechanisms of belimumab-rituximab sequential therapy across multiple body compartments in the setting of AAV.

Trial registration

ClinicalTrials.gov NCT03967925. Registered on May 30, 2019.
Core protocol for the adaptive Platform Trial In COVID-19 Vaccine priming and BOOsting (PICOBOO)
Authors: McLeod C. , Ramsay J , Flanagan K. L. , Plebanski M. , Marshall H. , Dymock M. , Marsh J. , Estcourt M. J. , Wadia U. , Williams P. C. M. , Tjiam M. C. , Blyth C. , Subbarao K. , Nicholson S. , Faust S. , Thornton R. B. , Mckenzie A. , Snelling T. L , Richmond P.
Published: March 2023

Background

The need for coronavirus 2019 (COVID-19) vaccination in different age groups and populations is a subject of great uncertainty and an ongoing global debate. Critical knowledge gaps regarding COVID-19 vaccination include the duration of protection offered by different priming and booster vaccination regimens in different populations, including homologous or heterologous schedules; how vaccination impacts key elements of the immune system; how this is modified by prior or subsequent exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and future variants; and how immune responses correlate with protection against infection and disease, including antibodies and effector and T cell central memory.

Methods

The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, Bayesian, adaptive, randomised controlled platform trial. PICOBOO will expeditiously generate and translate high-quality evidence of the immunogenicity, reactogenicity and cross-protection of different COVID-19 priming and booster vaccination strategies against SARS-CoV-2 and its variants/subvariants, specific to the Australian context. While the platform is designed to be vaccine agnostic, participants will be randomised to one of three vaccines at trial commencement, including Pfizer’s Comirnaty, Moderna’s Spikevax or Novavax’s Nuvaxovid COVID-19 vaccine. The protocol structure specifying PICOBOO is modular and hierarchical. Here, we describe the Core Protocol, which outlines the trial processes applicable to all study participants included in the platform trial.

Discussion

PICOBOO is the first adaptive platform trial evaluating different COVID-19 priming and booster vaccination strategies in Australia, and one of the few established internationally, that is designed to generate high-quality evidence to inform immunisation practice and policy. The modular, hierarchical protocol structure is intended to standardise outcomes, endpoints, data collection and other study processes for nested substudies included in the trial platform and to minimise duplication. It is anticipated that this flexible trial structure will enable investigators to respond with agility to new research questions as they arise, such as the utility of new vaccines (such as bivalent, or SARS-CoV-2 variant-specific vaccines) as they become available for use.

Trial registration

Australian and New Zealand Clinical Trials Registry ACTRN12622000238774. Registered on 10 February 2022.
Impact of corticosteroids on the duration of ventilatory support during severe acute exacerbations of chronic obstructive pulmonary disease in patients in the intensive care unit: a study protocol for a multicentre, randomized, placebo-controlled, double-blind trial
Authors: Ferré Alexis , Thille Arnaud W. , Mekontso-Dessap Armand , Similowski Thomas , Legriel Stéphane , Aegerter Philippe , Demoule Alexandre ,   The Réseau Européen de Recherche en Ventilation Artificielle (REVA) research network
Published: March 2023

Background

Patients who are admitted to the intensive care unit (ICU) for severe acute exacerbations of chronic obstructive pulmonary disease (COPD) have poor outcomes. Although international clinical practice guidelines cautiously recommend the routine use of systemic corticosteroids for COPD exacerbations, data are scarce and inconclusive regarding their benefit for most severe patients who require mechanical ventilation in the ICU. Furthermore, corticosteroids may be associated with an increased risk of infection, ICU-acquired limb weakness, and metabolic disorders.

Methods and analysis

This study is an investigator-initiated, multicentre, randomized, placebo-controlled, double-blind trial comparing systemic corticosteroids to placebo during severe acute exacerbations of COPD in patients who require mechanical ventilation in French ICUs. A total of 440 patients will be randomized 1:1 to methylprednisolone (1 mg/kg) or placebo for 5 days, and stratified according to initial mechanical ventilation (non-invasive or invasive), pneumonia as triggering factor, and recent use of systemic corticosteroids (< 48 h). The primary outcome is the number of ventilator-free days at day 28, defined as the number of days alive and without mechanical invasive and/or non-invasive ventilation between randomization and day 28. Secondary outcomes include non-invasive ventilation (NIV) failure rate, duration of mechanical ventilation (invasive and/or NIV), circulatory support (vasopressor), outcomes related to corticosteroid adverse events (severe hyperglycaemia, gastrointestinal bleeding, uncontrolled arterial hypertension, ICU-acquired weakness, ICU-acquired infections, and delirium), lengths of ICU and hospital stay, ICU and hospital mortality, day 28 and day 90 mortality, number of new exacerbation(s)/hospitalization(s) between hospital discharge and day 90, and dyspnoea and comfort at randomization, ICU discharge, and day 90. Subgroup analyses for the primary outcome are planned according to stratification criteria at randomization.
Enantioseparation, quantification, molecular docking and molecular dynamics study of five β-adrenergic blockers on Lux-Cellulose-2 column
Authors: Saleh Ola Ahmed , Badawey Amr Mohamed , Aboul-Enein Hassan Y. , Fouad Marwa Ahmed
Published: March 2023

Enantioseparation of five β-adrenergic blockers was studied using two mobile phases on a cellulose tris(3‐chloro‐4‐methylphenylcarbamate) (Lux-Cellulose-2) chiral column in normal phase mode. The first mobile phase composed of n-hexane: ethanol: diethylamine 60: 40: 0.1 by volume has successfully resolved the chromatographic peaks of three pairs of β-adrenergic blockers namely, bisoprolol, carvedilol and atenolol. A mixture of n-hexane: ethanol: diethyl amine 75: 25: 0.1 by volume was used as the second mobile phase to separate the four pairs of enantiomers, metoprolol, carvedilol, nebivolol and atenolol with high resolution values. The mobile phases were pumped at a flow rate 1 mL/min with column temperature 25 °C using a UV detector at 230 nm. Molecular docking simulations of the five pairs of enantiomers was carried out in the cavities of the chiral stationary phase to gain a better understanding of the interaction between analyte enantiomers and chiral stationary phase and to better understand the mechanism of chiral recognition. According to the results, hydrogen bond interactions and π-π- interactions were the main types of interaction involved in the chiral recognition. Molecular dynamics simulation was performed to investigate the solvent effect on the interaction of the five pair of enantiomers in the chiral stationary phase cavity under dynamic conditions.
Rapid screening of secondary aromatic metabolites in Populus trichocarpa leaves
Authors: Harman-Ware Anne E. , Martin Madhavi Z. , Engle Nancy L. , Doeppke Crissa , Tschaplinski Timothy J.
Published: March 2023

Background

High-throughput metabolomics analytical methodology is needed for population-scale studies of bioenergy-relevant feedstocks such as poplar (Populus sp.). Here, the authors report the relative abundance of extractable aromatic metabolites in Populus trichocarpa leaves rapidly estimated using pyrolysis-molecular beam mass spectrometry (py-MBMS). Poplar leaves were analyzed in conjunction with and validated by GC/MS analysis of extracts to determine key spectral features used to build PLS models to predict the relative composition of extractable aromatic metabolites in whole poplar leaves.

Results

The Pearson correlation coefficient for the relative abundance of extractable aromatic metabolites based on ranking between GC/MS analysis and py-MBMS analysis of the Boardman leaf set was 0.86 with R2 = 0.76 using a simplified prediction approach from select ions in MBMS spectra. Metabolites most influential to py-MBMS spectral features in the Clatskanie set included the following compounds: catechol, salicortin, salicyloyl-coumaroyl-glucoside conjugates, α-salicyloylsalicin, tremulacin, as well as other salicylates, trichocarpin, salicylic acid, and various tremuloidin conjugates. Ions in py-MBMS spectra with the highest correlation to the abundance of extractable aromatic metabolites as determined by GC/MS analysis of extracts, included m/z 68, 71, 77, 91, 94, 105, 107, 108, and 122, and were used to develop the simplified prediction approach without PLS models or a priori measurements.

Conclusions

The simplified py-MBMS method is capable of rapidly screening leaf tissue for relative abundance of extractable aromatic secondary metabolites to enable prioritization of samples in large populations requiring comprehensive metabolomics that will ultimately inform plant systems biology models and advance the development of optimized biomass feedstocks for renewable fuels and chemicals.
Unveiling the underlying molecular mechanisms of high lutein production efficiency in Chlorella sorokiniana FZU60 under a mixotrophy/photoautotrophy two-stage strategy by transcriptomic, physiological, and biochemical analyses
Authors: Ma Ruijuan , Zhang Zhen , Fang Hong , Liu Xinyu , Ho Shih-Hsin , Xie Youping , Chen Jianfeng
Published: March 2023

Background

Chlorella sorokinianaFZU60 is a promising lutein producing microalga. A mixotrophy/photoautotrophy two-stage strategy can achieve high biomass concentration at stage 1 and high lutein content at stage 2, leading to excellent lutein production efficiency inC. sorokinianaFZU60. However, the underlying molecular mechanisms are still unclear, restraining the further improvement of lutein production.

Results

In this study, physiological and biochemical analysis revealed that photochemical parameters (Fv/Fm and NPQ) and photosynthetic pigments contents increased during the shift from mixotrophy to photoautotrophy, indicating that photosynthesis and photoprotection enhanced. Furthermore, transcriptomic analysis revealed that the glyoxylate cycle and TCA cycle were suppressed after the shift to photoautotrophy, leading to a decreased cell growth rate. However, the gene expression levels of photosynthesis, CO2fixation, autophagy, and lutein biosynthesis were upregulated at the photoautotrophy stage, demonstrating that microalgal cells could obtain more precursor to synthesize lutein for enhancing photosynthesis and reducing reactive oxygen species.

Conclusions

The findings help to elucidate the molecular mechanisms for high lutein production efficiency ofC. sorokinianaFZU60 under the mixotrophy/photoautotrophy strategy, identify key functional genes responsible for lutein biosynthesis, and shed light on further improvement of lutein production by genetic or metabolic engineering in future studies.
Range of metastrongylids (superfamily Metastrongyloidea) of public health and veterinary concern present in livers of the endemic lizard Gallotia galloti of Tenerife, Canary Islands, Spain
Authors: Izquierdo-Rodriguez Elena , Anettová Lucia , Hrazdilová Kristýna , Foronda Pilar , Modrý David
Published: March 2023

Background

Endemic lizards of the genus Gallotia are of high ecological value to the terrestrial ecosystem of the archipelago of the Canary Islands, being potent seed spreaders as well as an important component of the diet of other vertebrates. The endemic lizard Gallotiagalloti in Tenerife has recently been reported to be a paratenic host of Angiostrongyluscantonensis, an invasive metastrongylid with zoonotic potential that is associated with rats as definitive hosts. However, microscopic examination of G.galloti tissue samples also revealed the presence of other metastrongylid larvae inside granulomas on the liver of this reptile. The aim of this study was to investigate the presence of helminths other than A.cantonensis in tissues of G.galloti from Tenerife.

Methods

A multiplex-nested PCR targeting the internal transcribed spacer 1 was designed that enabled the species-specific detection of A.cantonensis, Angiostrongylusvasorum, Aelurostrongylusabstrusus, Crenosomastriatum and Crenosomavulpis. Liver samples from 39 G.galloti were analysed.

Results

Five metastrongylids were detected: A.cantonensis (15.4% of samples analysed), A.vasorum (5.1%), Ae.abstrusus (30.8%), C.striatum (30.8%) and undetermined metastrongylid sequences (12.8%). Co-infection was highly prevalent among the lizards which tested positive.

Conclusions

The study provides a new specific tool for the simultaneous detection of a range of metastrongylids of veterinary importance as well as new data on the circulation of metastrongylids in an ecosystem dominated by lizards.

Graphical Abstract
Insecticidal activity of Simparica and Simparica Trio against Aedes aegypti in dogs
Authors: Geurden Thomas , Chapin Sara , McCall John W. , Mansour Abdelmoneim , Mahabir Sean P. , Kryda Kristina , McTier Tom
Published: March 2023

Background

Aedes aegypti is one of the main species responsible for the transmission of mosquito-borne pathogens worldwide. The isoxazoline Sarolaner has excellent efficacy as an acaricide against ticks and mites and as an insecticide against fleas, and potential efficacy against other insects.

Methods

In each of two laboratory studies, 24 dogs were randomly allocated (n = 8/group) to an untreated control group, a Simparica-treated group (at the minimum dose of 2.0 mg/kg sarolaner), or a Simparica Trio-treated group (at the minimum dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel), based on pre-treatment mosquito counts. Treatments were administered orally once on day 0. Each dog was exposed to 50 unfed female adult A. aegypti mosquitoes for 1 h on days 1, 7, 14, 21, 28 and 35. After each exposure, mosquitoes were counted for each dog and characterized as live, moribund or dead, and as fed or unfed. Dead mosquitoes were counted and removed at 12, 24 and 48 h post-exposure in study 1 and at 24, 48, 72, 96 and 120 h post-exposure in study 2. In study 2, mosquito eggs were collected from 72 h post-exposure until 120 h post-exposure. Insecticidal efficacy was calculated based on the reduction of the arithmetic mean live fed-mosquito counts in each of the treated groups versus the untreated control group for every timepoint post-exposure.

Results

Adequate challenge was demonstrated in both studies, with arithmetic mean live fed-mosquito counts ranging from 35.5 to 45.0 for the untreated group. Mean mosquito counts for dogs treated with Simparica and Simparica Trio were significantly (P < 0.0001) reduced within 48 h after exposure on all study days. In study 1, Simparica treatment provided ≥ 96.8% reduction in the arithmetic mean live fed-mosquito counts for 28 days, and Simparica Trio treatment provided ≥ 90.3% reduction for 21 days. In study 2, Simparica treatment provided ≥ 99.4% reduction for 35 days (from 48 h onwards), and Simparica Trio treatment provided ≥ 97.8% reduction for 28 days (from 72 h onwards).

Conclusions

Both studies demonstrated that a single oral dose of Simparica or Simparica Trio provides high efficacy against mosquitoes in dogs within 24–72 h after exposure for an entire month.

Graphical Abstract
Pharmacogenomic profiling reveals molecular features of chemotherapy resistance in IDH wild-type primary glioblastoma
Authors: Nam Yoonhee , Koo Harim , Yang Yingxi , Shin Sang , Zhu Zhihan , Kim Donggeon , Cho Hee Jin , Mu Quanhua , Choi Seung Won , Sa Jason K. , Seo Yun Jee , Kim Yejin , Lee Kyoungmin , Oh Jeong-Woo , Kwon Yong-Jun , Park Woong-Yang , Kong Doo-Sik , Seol Ho Jun , Lee Jung-Il , Park Chul-Kee , Lee Hye Won , Yoon Yeup , Wang Jiguang
Published: March 2023

Background

Although temozolomide (TMZ) has been used as a standard adjuvant chemotherapeutic agent for primary glioblastoma (GBM), treating isocitrate dehydrogenase wild-type (IDH-wt) cases remains challenging due to intrinsic and acquired drug resistance. Therefore, elucidation of the molecular mechanisms of TMZ resistance is critical for its precision application.

Methods

We stratified 69 primary IDH-wt GBM patients into TMZ-resistant (n= 29) and sensitive (n= 40) groups, using TMZ screening of the corresponding patient-derived glioma stem-like cells (GSCs). Genomic and transcriptomic features were then examined to identify TMZ-associated molecular alterations. Subsequently, we developed a machine learning (ML) model to predict TMZ response from combined signatures. Moreover, TMZ response in multisector samples (52 tumor sectors from 18 cases) was evaluated to validate findings and investigate the impact of intra-tumoral heterogeneity on TMZ efficacy.

Results

In vitro TMZ sensitivity of patient-derived GSCs classified patients into groups with different survival outcomes (P= 1.12e−4 for progression-free survival (PFS) and 3.63e−4 for overall survival (OS)). Moreover, we found that elevated gene expression ofEGR4,PAPPA,LRRC3, andANXA3was associated to intrinsic TMZ resistance. In addition, other features such as 5-aminolevulinic acid negative, mesenchymal/proneural expression subtypes, and hypermutation phenomena were prone to promote TMZ resistance. In contrast, concurrent copy-number-alteration inPTEN,EGFR, andCDKN2A/Bwas more frequent in TMZ-sensitive samples (Fisher’s exactP= 0.0102), subsequently consolidated by multi-sector sequencing analyses. Integrating all features, we trained a ML tool to segregate TMZ-resistant and sensitive groups. Notably, our method segregated IDH-wt GBM patients from The Cancer Genome Atlas (TCGA) into two groups with divergent survival outcomes (P= 4.58e−4 for PFS and 3.66e−4 for OS). Furthermore, we showed a highly heterogeneous TMZ-response pattern within each GBM patient using in vitro TMZ screening and genomic characterization of multisector GSCs. Lastly, the prediction model that evaluates the TMZ efficacy for primary IDH-wt GBMs was developed into a webserver for public usage (http://www.wang-lab-hkust.com:3838/TMZEP).

Conclusions

We identified molecular characteristics associated to TMZ sensitivity, and illustrate the potential clinical value of a ML model trained from pharmacogenomic profiling of patient-derived GSC against IDH-wt GBMs.
Automated prioritization of sick newborns for whole genome sequencing using clinical natural language processing and machine learning
Authors: Peterson Bennet , Hernandez Edgar Javier , Hobbs Charlotte , Malone Jenkins Sabrina , Moore Barry , Rosales Edwin , Zoucha Samuel , Sanford Erica , Bainbridge Matthew N. , Frise Erwin , Oriol Albert , Brunelli Luca , Kingsmore Stephen F. , Yandell Mark
Published: March 2023

Background

Rapidly and efficiently identifying critically ill infants for whole genome sequencing (WGS) is a costly and challenging task currently performed by scarce, highly trained experts and is a major bottleneck for application of WGS in the NICU. There is a dire need for automated means to prioritize patients for WGS.

Methods

Institutional databases of electronic health records (EHRs) are logical starting points for identifying patients with undiagnosed Mendelian diseases. We have developed automated means to prioritize patients for rapid and whole genome sequencing (rWGS and WGS) directly from clinical notes. Our approach combines a clinical natural language processing (CNLP) workflow with a machine learning-based prioritization tool named Mendelian Phenotype Search Engine (MPSE).

Results

MPSE accurately and robustly identified NICU patients selected for WGS by clinical experts from Rady Children’s Hospital in San Diego (AUC 0.86) and the University of Utah (AUC 0.85). In addition to effectively identifying patients for WGS, MPSE scores also strongly prioritize diagnostic cases over non-diagnostic cases, with projected diagnostic yields exceeding 50% throughout the first and second quartiles of score-ranked patients.

Conclusions

Our results indicate that an automated pipeline for selecting acutely ill infants in neonatal intensive care units (NICU) for WGS can meet or exceed diagnostic yields obtained through current selection procedures, which require time-consuming manual review of clinical notes and histories by specialized personnel.
Response to “Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany”
Authors: Zhou Avery , Babiker Fatima , Philip Andrew M. , Anesi Stephen D. , Foster C. Stephen
Published: March 2023

We have read the article entitled “Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany” by Heiligenhaus et al. While we appreciate the work conducted by the authors, we have several comments we would like to address. First, the follow-up interval of 2 years is too short to conclude that the clinical course between two chronic pathologies is not significantly different. Second, remission status was determined by uveitis inactivity during the 2-year follow-up visit without any mention of flare frequency or length of remission, which is not a reliable measure of uveitis control. Third, ANA-positive idiopathic anterior uveitis is not a classification with a distinct clinical phenotype, and additional reports of serologic investigations would have been helpful.
Fecal microbiota from MRL/lpr mice exacerbates pristane-induced lupus
Authors: Yi Xiaoqing , Huang Cancan , Huang Chuyi , Zhao Ming , Lu Qianjin
Published: March 2023

Background

The roles of gut microbiota in the pathogenesis of SLE have been receiving much attention during recent years. However, it remains unknown how fecal microbiota transplantation (FMT) and microbial metabolites affect immune responses and lupus progression.

Methods

We transferred fecal microbiota from MRL/lpr (Lpr) mice and MRL/Mpj (Mpj) mice or PBS to pristane-induced lupus mice and observed disease development. We also screened gut microbiota and metabolite spectrums of pristane-induced lupus mice with FMT via 16S rRNA sequencing, metagenomic sequencing, and metabolomics, followed by correlation analysis.

Results

FMT from MRL/lpr mice promoted the pathogenesis of pristane-induced lupus and affected immune cell profiles in the intestine, particularly the plasma cells. The structure and composition of microbial communities in the gut of the FMT-Lpr mice were different from those of the FMT-Mpj mice and FMT-PBS mice. The abundances of specific microbes such as prevotella taxa were predominantly elevated in the gut microbiome of the FMT-Lpr mice, which were positively associated with functional pathways such as cyanoamino acid metabolism. Differential metabolites such as valine and L-isoleucine were identified with varied abundances among the three groups. The abundance alterations of the prevotella taxa may affect the phenotypic changes such as proteinuria levels in the pristane-induced lupus mice.

Conclusion

These findings further confirm that gut microbiota play an important role in the pathogenesis of lupus. Thus, altering the gut microbiome may provide a novel way to treat lupus.
Clinical characteristics of rheumatoid arthritis patients with interstitial lung disease: baseline data of a single-center prospective cohort
Authors: Kim Hyoungyoung , Cho Soo-Kyung , Song Yeo-Jin , Kang Juyeon , Jeong Seung-A , Kim Hye Won , Choi Chan-Bum , Kim Tae-Hwan , Jun Jae-Bum , Bae Sang-Cheol , Yoo Dae-Hyun , Lee Hyun , Park Dong Won , Sohn Jang Won , Yoon Ho Joo , Hong Su Jin , Yoo Seung-Jin , Choi Yo Won , Lee Youkyung , Kim Sang Heon , Sung Yoon-Kyoung
Published: March 2023

Background

To introduce a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features in comparison with RA patients without ILD.

Methods

Using a multidisciplinary collaborative approach, a single-center cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 were used to compare the clinical features of RA patients without ILD (RA-non ILD). Multivariable logistic regression analysis was used to identify factors associated with ILD in RA patients.

Results

Among 148 RA-ILD and 410 RA-non ILD patients, participants in the RA-ILD group were older (65.8 ± 9.9 vs. 58.0 ± 10.4 years, P < 0.001) and included more males (35.8% vs. 14.6%, P < 0.001) than in the RA-non ILD group. The RA-ILD group had a higher proportion of late-onset RA patients (age ≥ 60 years) than in the comparator group (43.9% vs. 14.2%, P < 0.001). Multivariable logistic regression analysis showed that higher age at RA onset (OR 1.056, 95% CI 1.021–1.091), higher body mass index (BMI; OR 1.65, 95% CI 1.036–2.629), smoking history (OR 2.484, 95% CI 1.071–5.764), and oral glucocorticoid use (OR 3.562, 95% CI 2.160–5.874) were associated with ILD in RA patients, whereas methotrexate use was less likely to be associated with ILD (OR 0.253, 95% CI 0.155–0.412).

Conclusions

Higher age at RA onset, smoking history, and higher BMI were associated with the presence of ILD among RA patients. Oral glucocorticoids were more frequently used whereas methotrexate was less likely to be used in RA-ILD patients.
Utility of hand-held ultrasound for image acquisition and interpretation by trained Kenyan providers
Authors: Wanjiku Grace , Dreizler Lindsay , Wu Shirley , Baird Janette , Wachira Benjamin
Published: March 2023

Background

Point-of-care ultrasound (POCUS) plays a prominent role in the timely recognition and management of multiple medical, surgical, and obstetric conditions. A POCUS training program for primary healthcare providers in rural Kenya was developed in 2013. A significant challenge to this program is the acquisition of reasonably priced ultrasound machines with adequate image quality and the ability to transmit images for remote review. The goal of this study is to compare the utility of a smartphone-connected, hand-held ultrasound with a traditional ultrasound device for image acquisition and interpretation by trained healthcare providers in Kenya.

Methods

This study took place during a routine re-training and testing session for healthcare providers who had already received POCUS training. The testing session involved a locally validated Observed Structured Clinical Exam (OSCE) that assessed trainees’ skills in performing the Extended Focused Assessment with Sonography for Trauma (E-FAST) and focused obstetric exams. Each trainee performed the OSCE twice, once using a smartphone-connected hand-held ultrasound and once using their notebook ultrasound model.

Results

Five trainees obtained a total of 120 images and were scored on image quality and interpretation. Overall E-FAST imaging quality scores were significantly higher for the notebook ultrasound compared to the hand-held ultrasound but there was no significant difference in image interpretation. Overall focused obstetric image quality and image interpretation scores were the same for both ultrasound systems. When separated into individual E-FAST and focused obstetric views, there were no statistically significant differences in the image quality or image interpretation scores between the two ultrasound systems. Images obtained using the hand-held ultrasound were uploaded to the associated cloud storage using a local 3G-cell phone network. Upload times were 2–3 min.

Conclusion

Among POCUS trainees in rural Kenya, the hand-held ultrasound was found to be non-inferior to the traditional notebook ultrasound for focused obstetric image quality, focused obstetric image interpretation, and E-FAST image interpretation. However, hand-held ultrasound use was found to be inferior for E-FAST image quality. These differences were not observed when evaluating each E-FAST and focused obstetric views separately. The hand-held ultrasound allowed for rapid image transmission for remote review.
Start spreading the news: a deliberate approach to POCUS program development and implementation
Authors: Gaudreau-Simard Mathilde , Kilabuk Elaine , Halman Samantha , Wooller Krista , Woo Michael Y. , Arntfield Robert , Ma Irene , Forster Alan J.
Published: March 2023

While there is an expanding body of literature on Point-of-Care Ultrasound (POCUS) pedagogy, administrative elements that are necessary for the widespread adoption of POCUS in the clinical environment have received little attention. In this short communication, we seek to address this gap by sharing our institutional experience with POCUS program development and implementation. The five pillars of our program, selected to tackle local barriers to POCUS uptake, are education, workflow, patient safety, research, and sustainability. Our program logic model outlines the inputs, activities, and outputs of our program. Finally, key indicators for the monitoring of program implementation efforts are presented. Though designed for our local context, this approach may readily be adapted toward other clinical environments. We encourage others leading the integration of POCUS at their centers to adopt this approach not only to achieve sustainable change but also to ensure that quality safeguards are in place.
Inter-observer and intra-observer variability in ultrasound assessment of gastric content and volume in critically ill patients receiving enteral nutrition
Authors: Ruiz Ávila Héctor Andrés , Espinosa Almanza Carmelo José , Fuentes Barreiro Cindy Yohana
Published: March 2023

Background

The assessment of gastric content and volume using bedside ultrasound (US) has become a useful tool in emergency departments, anesthesiology departments and inpatient wards, as it provides a rapid and dynamic assessment of the gastric content of patients, which, allows making decisions regarding the risk of regurgitation or the need to adjust the strategy used to induce general anesthesia in patients with a full stomach. This assessment consists of two evaluations: a qualitative one, in which the status of the antrum, in terms of gastric content, is classified into three categories (empty, liquid content and full), and a quantitative one, where gastric volume is estimated. The objective of this study was to estimate the intra-observer and inter-observer agreement in ultrasound assessment of gastric content and volume in critically ill patients receiving enteral nutrition.

Results

A total of 41 patients were included and each examiner performed 64 gastric US (n = 128). Participants’ average age was 56.5 years (SD ± 12.6) and 63.4% were men. Regarding the qualitative evaluation of the antrum, in supine position both examiners classified the gastric content as grade 0 in 1 gastric US (1.5%), grade 1 in 4 gastric US (6.2%) and grade 2 in 59 (92.1%). Regarding intra-observer variability in the measurement of the area of the antrum, Lin's concordance correlation coefficient (CCC), the difference of means between measurements and the 95% limits of agreement of Bland and Altman values were 0.95 (95% CI 0.940–0.977), − 0.47 cm2 (SD ± 1.64) and − 3.70 cm2 to 2.75 cm2, respectively, in EC1, and 0.94 (95% CI 0.922–0.973), − 0.18 cm2 (SD ± 2.18) and − 4.47 cm2 to 4.09 cm2 in EC2. Concerning to inter-observer variability (EC1 vs EC2) in the measurement of the area of the antrum and of gastric volume, the following CCC, mean difference between measurements and 95% limits of agreement of Bland and Altman values were obtained: measurement of the area of the antrum: 0.84 (95% CI 0.778–0.911), − 0.86 cm2 (SD ± 3.38) and − 7.50 cm2 to 5.78 cm2; gastric volume measurement: 0.84 (95% CI 0.782–0.913), − 12.3 mL (SD ± 49.2) and − 108.8 mL to 84.0 mL.

Conclusions

The assessment of gastric content and volume using bedside US in critically ill patients on mechanical ventilation and receiving enteral nutrition showed a good intra and inter-rater reliability. Most of the patients included in the study had a high risk of pulmonary aspiration, since, according to the results of the gastric US evaluation, they had gastric volumes > 1.5 mL/kg.
Association of triglyceride-glucose index with atherosclerotic cardiovascular disease and mortality among familial hypercholesterolemia patients
Authors: Wen Jun , Pan Qi , Du Lei-Lei , Song Jing-Jing , Liu Yu-Peng , Meng Xiang-Bin , Zhang Kuo , Gao Jun , Shao Chun-Li , Wang Wen-Yao , Zhou Hao , Tang Yi-Da
Published: March 2023

Background

Familial hypercholesterolemia (FH) is an inherited metabolic disorder with a high level of low-density lipoprotein cholesterol and the worse prognosis. The triglyceride-glucose (TyG) index, an emerging tool to reflect insulin resistance (IR), is positively associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) in healthy individuals, but the value of TyG index has never been evaluated in FH patients. This study aimed to determine the association between the TyG index and glucose metabolic indicators, insulin resistance (IR) status, the risk of ASCVD and mortality among FH patients.

Methods

Data from National Health and Nutrition Examination Survey (NHANES) 1999–2018 were utilized. 941 FH individuals with TyG index information were included and categorized into three groups: < 8.5, 8.5–9.0, and > 9.0. Spearman correlation analysis was used to test the association of TyG index and various established glucose metabolism-related indicators. Logistic and Cox regression analysis were used to assess the association of TyG index with ASCVD and mortality. The possible nonlinear relationships between TyG index and the all-cause or cardiovascular death were further evaluated on a continuous scale with restricted cubic spline (RCS) curves.

Results

TyG index was positively associated with fasting glucose, HbA1c, fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) index (all p < 0.001). The risk of ASCVD increased by 74% with every 1 unit increase of TyG index (95%CI: 1.15–2.63, p = 0.01). During the median 114-month follow-up, 151 all-cause death and 57 cardiovascular death were recorded. Strong U/J-shaped relations were observed according to the RCS results (p = 0.0083 and 0.0046 for all-cause and cardiovascular death). A higher TyG index was independently associated with both all-cause death and cardiovascular death. Results remained similar among FH patients with IR (HOMA-IR ≥ 2.69). Moreover, addition of TyG index showed helpful discrimination of both survival from all-cause death and cardiovascular death (p < 0.05).

Conclusion

TyG index was applicable to reflect glucose metabolism status in FH adults, and a high TyG index was an independent risk factor of both ASCVD and mortality.
Association between antidepressant use and liver fibrosis in patients with type 2 diabetes: a population based study
Authors: Shi Lin , Jia Fangyuan
Published: March 2023

Background

The prevalence of liver fibrosis among diabetic patients is increasing rapidly. Our study aims at exploring the relationship between antidepressant use and liver fibrosis in diabetic patients.

Methods

We conducted this cross-sectional study through the cycle of National Health and Nutrition Examination Survey (NHANES) 2017–2018. The study population were consisted of patients with type 2 diabetes and reliable vibration-controlled transient elastography (VCTE) results. The presence of liver fibrosis and steatosis were assessed by the median values of liver stiffness measurement (LSM) and controlled attenuation parameter (CAP), respectively. Antidepressants included selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and serotonin antagonists and reuptake inhibitors (SARIs). Patients with evidence of viral hepatitis and significant alcohol consumption were excluded. Logistic regression analysis was performed to evaluate the association between antidepressant use and both steatosis and significant (≥ F3) liver fibrosis after adjustment for potential confounders.

Results

Our study population consisted of 340 women and 414 men, of whom 87 women(61.3%) and 55(38.7%) men received antidepressants. The most commonly used antidepressants were SSNIs(48.6%), SNRIs(22.5%) and TCAs(12.7%), followed by SARIs(10.6%) and other antidepressants(5.6%). 165 participants had significant liver fibrosis by VCTE, with a weighted overall prevalence of 24%(95% CI 19.2–29.5). In addition, 510 patients had evidence of hepatic steatosis by VCTE with a weighted overall prevalence of 75.4%(95% CI 69.2–80.7). After adjusting confounders, no significant association was observed between antidepressant use and significant liver fibrosis or cirrhosis.

Conclusions

In conclusion, in this cross-sectional study, we found that antidepressant drugs was not associated with liver fibrosis and cirrhosis in patients with type 2 diabetes in a nationwide population.
Age- and sex-specific differences in the association of serum osteocalcin and cardiometabolic risk factors in type 2 diabetes
Authors: Li Wei , Wang Yan , Dong Jie , Di Ruiqing , Liu Xiaojun , Liu Shengyun
Published: March 2023

Background

Serum osteocalcin levels are closely related to metabolic syndrome and cardiovascular disease. This study aimed to investigate the relationship between serum osteocalcin levels and cardiometabolic risk factors in patients with type 2 diabetes (T2D) according to age and sex.

Methods

This cross-sectional study included 1500 patients with T2D (991 men and 509 women) aged ≥ 18 years old. The age- and sex-specific disparities in glycemic and lipid control, as well as cardiometabolic risk factors were evaluated.

Results

The levels of serum osteocalcin were significantly higher in women aged > 50 years compared with women aged ≤ 50 years (15.6 ± 6.5 ng/mL vs. 11.3 ± 4.5 ng/mL, p < 0.0001). However, this was lower in men aged > 50 years than men aged ≤ 50 years (12.2 ± 4.2 ng/mL vs. 12.9 ± 4.3 ng/mL, p = 0.0081). We performed correlation analyses of serum osteocalcin and cardiometabolic parameters. Serum osteocalcin concentrations were negative associated with FBG and HbA1c levels in women and men ≤ 50 years old, but not in men aged > 50 years old. Serum osteocalcin were negatively correlated with TG and positively correlated with HDL-C and LDL-C only in men aged ≤ 50 years. In binary logistic regression analysis, serum osteocalcin levels were associated with multiple cardiovascular risk factors, as follows: overweight/obese (odds ratio [OR], 0.944; 95% confidence interval [CI], 0.9–0.991, p = 0.02) in men aged > 50 years; high HbA1C and high FBG in women and men aged ≤ 50 years, but not in men aged > 50 years; after adjustment for confounding factors, high TG (OR, 0.905; 95% CI 0.865–0.947, p < 0.0001), metabolic syndrome (OR, 0.914; 95% CI 0.874–0.956, p < 0.0001), and low high-density lipoprotein cholesterol (OR, 0.933; 95% CI, 0.893–0.975, p = 0.002) were seen in men aged ≤ 50 years only.

Conclusions

Serum osteocalcin level has significant relationships with cardiometabolic risk factors and several age- and sex-related differences in patients with T2D. Decreased serum osteocalcin levels are associated with a worse cardiometabolic risk profile.
Association of skeletal muscle mass and its change with diabetes occurrence: a population-based cohort study
Authors: Xu Yiting , Hu Tingting , Shen Yun , Wang Yufei , Bao Yuqian , Ma Xiaojing
Published: March 2023

Background

Low muscle mass likely results in reduced capacity for glucose disposal, leading to a significant but under-appreciated contribution to increasing the risk of diabetes. But few prospective studies have investigated the association between the loss of muscle mass and the occurrence of diabetes. We aimed to investigate whether short-term changes in muscle mass affect the incidence of diabetes in a Chinese population.

Methods

This study included 1275 individuals without evident diabetes at baseline. In the baseline and re-examination, individuals completed the risk factors survey and underwent body composition measurement. Muscle mass index was defined as the percentage skeletal muscle mass, which was measured by an automatic bioelectric analyzer.

Results

After a median follow-up of 2.1 years, 142 individuals developed diabetes (11.1%). There was an inverse association between basal skeletal muscle mass index and the risk of diabetes in participants with impaired glucose regulation but not in those with normal glucose tolerance. Multivariate-adjusted hazard ratios for the risk of developing diabetes were 0.85 (95% CI: 0.74–0.98) and 1.15 (95% CI: 0.98–1.34), respectively. Furthermore, Cox regression analysis revealed that a two-year change in skeletal muscle mass was also inversely associated with the incidence of diabetes in both participants with normal glucose tolerance and with impaired glucose regulation (HR: 0.76, 95% CI: 0.65–0.89; HR: 0.81, 95% CI: 0.71–0.91).

Conclusions

These findings emphasized the importance of early detection and control of muscle mass loss for the prevention of diabetes.