bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomised trial on modulating endogenous fibrinolysis in patients with acute coronary syndrome VaLiDate-R
Authors: Gue Y X , Kanji R , Wellsted D , Srinivasan M , Wyatt S , Gorog D
Published: June 2022

Funding Acknowledgements

Type of funding sources: Private company. Main funding source(s): This study is funded by Bayer PLC, 400 South Oak Way, Green Park, Reading, Berkshire, RG2 6AD.

Background

Impaired endogenous fibrinolysis is novel biomarker that can identify patients with ACS at increased cardiovascular risk. The addition of very low dose rivaroxaban (VLDR) to dual antiplatelet therapy has been shown to reduce cardiovascular events but at a cost of increased bleeding and is therefore not suitable for all-comers. Targeted additional pharmacotherapy with VLDR to improve endogenous fibrinolysis may improve outcomes in high-risk patients, whilst avoiding unnecessary bleeding in low-risk individuals.

Methods and Results

The VaLiDate-R study is an investigator-initiated, randomised, open-label, single centre trial comparing the effect of 3 antithrombotic regimens on endogenous fibrinolysis in 150 patients with ACS. Subjects whose screening blood test shows impaired fibrinolytic status (lysis time >2000s), will be randomised to one of 3 treatment arms in a 1:1:1 ratio: clopidogrel 75 mg daily (Group 1); clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily (Group 2); ticagrelor 90 mg twice daily (Group 3), in addition to aspirin 75 mg daily. Rivaroxaban will be given for 30 days. Fibrinolytic status will be assessed during admission and at 2, 4 and 8 weeks. The primary outcome measure is the change in fibrinolysis time from admission to 4 weeks follow-up, using the Global Thrombosis Test.

Conclusion

If VLDR can improve endogenous fibrinolysis in ACS, future large-scale studies would be required to assess whether targeted use of VLDR in patients with ACS and impaired fibrinolysis can translate into improved clinical outcomes, with reduction in major adverse cardiovascular events in this high-risk cohort.
Single cell profiling of adipose tissue in atherosclerosis
Authors: Thanigai Arasu U , Ord T , Liikkanen J , Kettunen S , Lonnberg T , Palani S , Yla-Herttuala S , Roivainen A , Kaikkonen MU
Published: June 2022

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): Academy of Finland

Sigrid Jusélius Foundation

Adipose tissue influences the physiological and pathological processes in our body by regulating lipid storage and metabolic homeostasis. Extracellular matrix (ECM) is a dynamic and complex assemblage consisting of polysaccharides, proteogylcans and signalling proteins. Though both adipocytes and non- adipose cells of the stromal fraction contribute to ECM maintenance, role of adipose tissue ECM in the disease remains poorly characterised. High fat diet (HFD) and obesity represent major risk factors for atherosclerosis. Our overall aim in this study was to understand HFD induced changes in the adipose tissue during atherosclerosis progression using single cell RNA sequencing (scRNA-seq), to identify the ligands responsible for changes in the expression of ECM components and to characterise the role of ECM protein fibrillin in disease associated tissue changes.

We performed scRNA-seq in the adipose tissue of control mice and atherosclerotic LDLR-/- / ApoB100/100 subjected to 1 (early disease) or 3 months (advanced disease) of HFD. This allowed us to identify 13 different cell types in the adipose tissue of the diseased mice. Among them, we identified mesenchymal cells (MSC) undergoing changes from putatively adipogenic to fibrogenic cells. The differentially expressed genes in the MSC population exhibited functions related to ECM development, maintenance and signalling. We identified Fibrillin-1 (Fbn1) as one of the most prominent up regulated genes and studied the effect of Fbn1 knockout in ApoE-/- Fbn1C1039G+/- mice. The Fbn1 knockout mice model suited our experimental design to study the adipose tissue during atherosclerosis as the mice developed significantly large and unstable plaques characterised by large necrotic core. Our results demonstrated that adipose tissue expresses a new subtype with HFD in Fbn1 knockout mice, which could be associated with insulin resistance and fat accumulation. Fbn1 knockout led to an altered phenotype of MSCs (or adipocytes) in adipose tissue.

Altogether, our analysis provides the first steps toward understanding the role of MSCs in ECM-related changes during atherosclerosis and HFD stimulation.
Whole-genome sequencing analysis and protocol for RNA interference of the endoparasitoid waspAsobara japonica
Authors: Kamiyama Takumi , Shimada-Niwa Yuko , Tanaka Hiroyuki , Katayama Minami , Kuwabara Takayoshi , Mori Hitoha , Kunihisa Akari , Itoh Takehiko , Toyoda Atsushi , Niwa Ryusuke
Published: June 2022

Asobara japonica is an endoparasitic wasp that parasitizes Drosophila flies. It synthesizes various toxic components in the venom gland and injects them into host larvae during oviposition. To identify and characterize these toxic components for enabling parasitism, we performed the whole-genome sequencing (WGS) and devised a protocol for RNA interference (RNAi) with A. japonica. Because it has a parthenogenetic lineage due to Wolbachia infection, we generated a clonal strain from a single wasp to obtain highly homogenous genomic DNA. The WGS analysis revealed that the estimated genome size was 322 Mb with a heterozygosity of 0.132%. We also performed RNA-seq analyses for gene annotation. Based on the qualified WGS platform, we cloned ebony-Aj, which encodes the enzyme N-β-alanyl dopamine synthetase, which is involved in melanin production. The microinjection of double-stranded RNA (dsRNA) targeting ebony-Aj led to body colour changes in adult wasps, phenocopying ebony-Dm mutants. Furthermore, we identified putative venom genes as a target of RNAi, confirming that dsRNA injection-based RNAi specifically suppressed the expression of the target gene in wasp adults. Taken together, our results provide a powerful genetic toolkit for studying the molecular mechanisms of parasitism.
COVID-19 infection complicated with acute pulmonary embolism treated with percutaneous pulmonary artery thrombectomy: a case report
Authors: Petrov Ivo , Stankov Zoran , Dobrev Georgi , Polomski Petar
Published: June 2022

Background

Coronavirus disease 2019 (COVID-19) disease is a highly prothrombotic state. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are observed with increased incidence in patients infected with the severe acute respiratory syndrome coronavirus 2 virus.

Case summary

A 57-year-old male patient with a recent COVID-19 infection complained of leg swelling shortly after his COVID ward discharge. A few days later he was hospitalized with acute massive PE and DVT of his left leg was diagnosed. In another facility, as the first line of treatment, the PE was managed with catheter-directed therapy (CDT) using thrombus defragmentation via 5F (French) Pigtail catheter and supraselective application of 40 mg alteplase. Following the procedure, in addition, 50 mg alteplase was also applied as a 1 hour systemic infusion. Despite the haemodynamic stabilization of the patient, he remained persistently symptomatic and tachycardic. Three days later—in our institution, a second computed tomography pulmoangiography revealed massive thrombotic masses mainly in the left pulmonary artery. Successful percutaneous thrombus aspiration was conducted. The procedure was uneventful with an immediate drop of systolic pulmonary artery pressure from 68 to 47 mmHg and relief of the patient’s symptoms.

Discussion

In the era of the COVID-19 pandemic, physicians have to remain vigilant of its potential thrombotic complications, the most commonly observed being DVT and PE. We demonstrated the efficacy of percutaneous thrombus aspiration in a patient with acute COVID-19-associated PE, after initial CDT with thrombus defragmentation and high-dose tissue plasminogen activator was implemented with a suboptimal result.
Lipid A heterogeneity and its role in the host interactions with pathogenic and commensal bacteria
Authors: Saha Sukumar , Pupo Elder , Zariri Afshin , van der Ley Peter
Published: June 2022

Lipopolysaccharide (LPS) is for most but not all Gram-negative bacteria an essential component of the outer leaflet of the outer membrane. LPS contributes to the integrity of the outer membrane, which acts as an effective permeability barrier to antimicrobial agents and protects against complement-mediated lysis. In commensal and pathogenic bacteria LPS interacts with pattern recognition receptors (e.g LBP, CD14, TLRs) of the innate immune system and thereby plays an important role in determining the immune response of the host. LPS molecules consist of a membrane-anchoring lipid A moiety and the surface-exposed core oligosaccharide and O-antigen polysaccharide. While the basic lipid A structure is conserved among different bacterial species, there is still a huge variation in its details, such as the number, position and chain length of the fatty acids and the decoration of the glucosamine disaccharide with phosphate, phosphoethanolamine or amino sugars. New evidence has emerged over the last few decades on how this lipid A heterogeneity confers distinct benefits to some bacteria because it allows them to modulate host responses in response to changing host environmental factors. Here we give an overview of what is known about the functional consequences of this lipid A structural heterogeneity. In addition, we also summarize new approaches for lipid A extraction, purification and analysis which have enabled analysis of its heterogeneity.
VviAGL11 self-regulates and targets hormone- and secondary metabolism-related genes during seed development
Authors: Amato Alessandra , Cardone Maria Francesca , Ocarez Nallatt , Alagna Fiammetta , Ruperti Benedetto , Fattorini Chiara , Velasco Riccardo , Mejía Nilo , Zenoni Sara , Bergamini Carlo
Published: June 2022

VviAGL11, the Arabidopsis SEEDSTICK homolog, has been proposed to have a causative role in grapevine stenospermocarpy. An association between a mutation in the coding sequence (CDS) and the seedless phenotype was reported, however, no working mechanisms have been demonstrated yet. We performed a deep investigation of the full VviAGL11 gene sequence in a collection of grapevine varieties belonging to several seedlessness classes that revealed three different promoter-CDS combinations. By investigating the expression of the three VviAGL11 alleles, and by evaluating their ability to activate the promoter region, we observed that VviAGL11 self-activates in a specific promoter-CDS combination manner.

Furthermore, by transcriptomic analyses on ovule and developing seeds in seeded and seedless varieties and co-expression approaches, candidate VviAGL11 targets were identified and further validated through luciferase assay and in situ hybridization. We demonstrated that VviAGL11 Wild Type CDS activates Methyl jasmonate esterase and Indole-3-acetate beta-glucosyltransferase, both involved in hormone signaling and Isoflavone reductase, involved in secondary metabolism. The dominant-negative effect of the mutated CDS was also functionally ectopically validated in target induction. VviAGL11 was shown to co-localize with its targets in the outer seed coat integument, supporting its direct involvement in seed development, possibly by orchestrating the crosstalk among MeJA, auxin, and isoflavonoids synthesis.

In conclusion, the VviAGL11 expression level depends on the promoter-CDS allelic combination, and this will likely affect its ability to activate important triggers of the seed coat development. The dominant-negative effect of the mutated VviAGL11 CDS on the target genes activation was molecularly validated. A new regulatory mechanism correlating VviAGL11 haplotype assortment and seedlessness class in grapevine is proposed.
Narrating by Doing: A Bridging Concept for Understanding and Informing the Design of Tangible Interfaces for Storytelling
Authors: Sylla Cristina , Gil Maitê , Pereira Íris Susana Pires
Published: June 2022

We present and discuss the concept ‘narrating by doing’ as the process of creating narratives by performing different embodied actions with tangible interfaces for storytelling. We characterize it as a ‘bridging concept’ that can facilitate exchange between theory and design, informing research and design of TUIs for storytelling targeting young children. The concept builds on theories of cognition, learning and narration, specifically drawing upon the following perspectives: Constructionism, Socio-Constructivism, Embodied Cognition, Narratology and The Narrative Practice Hypothesis. Building upon these theoretical foundations, we identify and discuss four ‘design articulations’ (i.e. important parameters that express the qualities of the concept), namely communicative situation, narrative function of the tangible objects, collaborative and embodied actions and the narrator’s position. Finally, we add evidence to the concept and discuss its productiveness by presenting a set of considerations to inform the design of tangible interfaces for storytelling.
The harm of class imbalance corrections for risk prediction models: illustration and simulation using logistic regression
Authors: van den Goorbergh Ruben , van Smeden Maarten , Timmerman Dirk , Van Calster Ben
Published: June 2022

Objective

Methods to correct class imbalance (imbalance between the frequency of outcome events and nonevents) are receiving increasing interest for developing prediction models. We examined the effect of imbalance correction on the performance of logistic regression models.

Material and Methods

Prediction models were developed using standard and penalized (ridge) logistic regression under 4 methods to address class imbalance: no correction, random undersampling, random oversampling, and SMOTE. Model performance was evaluated in terms of discrimination, calibration, and classification. Using Monte Carlo simulations, we studied the impact of training set size, number of predictors, and the outcome event fraction. A case study on prediction modeling for ovarian cancer diagnosis is presented.

Results

The use of random undersampling, random oversampling, or SMOTE yielded poorly calibrated models: the probability to belong to the minority class was strongly overestimated. These methods did not result in higher areas under the ROC curve when compared with models developed without correction for class imbalance. Although imbalance correction improved the balance between sensitivity and specificity, similar results were obtained by shifting the probability threshold instead.

Discussion

Imbalance correction led to models with strong miscalibration without better ability to distinguish between patients with and without the outcome event. The inaccurate probability estimates reduce the clinical utility of the model, because decisions about treatment are ill-informed.

Conclusion

Outcome imbalance is not a problem in itself, imbalance correction may even worsen model performance.
Increased Repellent Effect of DEET on Aedes aegypti (Diptera: Culicidae) Field Population
Authors: Maia Pollyana Conceição Romão , La Corte Roseli , Pires Liandra Brasil , Banfield Lydia , Logan James G , Lima-Camara Tamara Nunes
Published: June 2022

Insecticides and repellents are routinely used in Brazil because of the high rates of arbovirus transmission and the nuisance caused by mosquitoes. However, few studies have assessed the effectiveness of repellents against mosquito populations that have been under exposure to xenobiotics, mainly insecticides and repellents. This study investigated the sensitivity of a field population of Aedes aegypti (Linnaeus, 1762) from a dengue-endemic area under high insecticide pressure to N,N-diethylmethylbenzamide (DEET), the active ingredient in common repellent products. The field (Laranjeiras, Sergipe, Brazil) and laboratory (Rockefeller) populations were characterized for the presence of the Val1016Ile kdr mutation, associated with pyrethroid resistance, and locomotor activity. Repellency bioassays were performed to assess the response of the mosquitoes to human odor by exposing them to 10% DEET applied to the skin in ethanol. Samples from the field population showed higher frequency of the kdr mutation, 21.9% homozygous and 21.9% heterozygous, greater locomotor activity and greater sensitivity to DEET than the laboratory population. These results suggest increased sensitivity to DEET in field populations and a possible interaction between insecticide exposure and sensitivity to DEET.
Considerations and recommendations for assessment of plasma protein binding and drug–drug interactions for siRNA therapeutics
Authors: Humphreys Sara C , Davis John A , Iqbal Sajida , Kamel Amin , Kulmatycki Kenneth , Lao Yanbin , Liu Xiumin , Rodgers John , Snoeys Jan , Vigil Adam , Weng Yan , Wiethoff Christopher M , Wittwer Matthias B
Published: June 2022

At the time of writing, although siRNA therapeutics are approved for human use, no official regulatory guidance specific to this modality is available. In the absence of guidance, preclinical development for siRNA followed a hybrid of the small molecule and biologics guidance documents. However, siRNA differs significantly from small molecules and protein-based biologics in its physicochemical, absorption, distribution, metabolism and excretion properties, and its mechanism of action. Consequently, certain reports typically included in filing packages for small molecule or biologics may benefit from adaption, or even omission, from an siRNA filing. In this white paper, members of the ‘siRNA working group’ in the IQ Consortium compile a list of reports included in approved siRNA filing packages and discuss the relevance of two in vitro reports—the plasma protein binding evaluation and the drug–drug interaction risk assessment—to support siRNA regulatory filings. Publicly available siRNA approval packages and the literature were systematically reviewed to examine the role of siRNA plasma protein binding and drug–drug interactions in understanding pharmacokinetic/pharmacodynamic relationships, safety and translation. The findings are summarized into two decision trees to help guide industry decide when in vitro siRNA plasma protein binding and drug–drug interaction studies are warranted.
Recurrent Skin and Soft Tissue Infection following Breast Reduction Surgery Caused by Gordonia bronchialis: A Case Report
Authors: Davidson Amelia L. , Driscoll Cassandra R. , Luther Vera P. , Katz Adam J.
Published: June 2022

The expanding knowledge of the breast microbiome and its constituents necessitates understanding of how it plays into human disease. Consideration of how to identify novel organisms in breast tissue is a topic of hot debate. We report a case of a 26-year-old woman with repeat incisional break-down and sanguinopurulent drainage who required repeat incision and drainage procedures after bilateral breast reduction. Cultures revealed no growth until 4 months postoperation when matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) revealed Gordonia bronchialis, a fastidious, slow-growing organism. To date, there are fewer than 30 reported cases of G. bronchialis infections and only one with breast involvement. Our patient required 6 weeks of amoxicillin-clavulanate therapy and frequent follow-up for symptom resolution. This case demonstrates the need for additional microbiologic data in patients with delayed, persistent infections after breast surgery.
Psychological Contributions to Symptom Provocation Testing After Concussion
Authors: Terpstra Alex R. , Louie Dennis R. , Iverson Grant L. , Yeates Keith Owen , Picon Edwina , Leddy John J. , Silverberg Noah D.
Published: June 2022

Objective:

Following concussion, symptoms such as headache, dizziness, and fatigue may transiently worsen or reemerge with increased exertion or activity. Standardized tests have been developed to assess symptom increases following aerobic, cognitive, or vestibular/oculomotor challenge. Although neurophysiological mechanisms are proposed to underlie symptom increases following exertion, psychological factors such as anxiety and misinterpretation of normal bodily sensations may also play a role. In this study, we examined the contribution of psychological factors to symptom provocation testing outcomes.

Setting:

Two outpatient concussion clinics in British Columbia, Canada.

Participants:

Adults with persistent symptoms following concussion (N = 79; 62% women).

Design:

In a single session, participants completed self-report questionnaires measuring the psychological factors of interest and underwent symptom provocation testing including aerobic (Buffalo Concussion Bike Test; BCBT), cognitive (National Institutes of Health Toolbox-Cognition Battery; NIHTB-CB), and vestibular/oculomotor (Vestibular/Ocular Motor Screening for Concussion; VOMS) challenge.

Main Measures:

Psychological factors of interest included premorbid and current anxiety (Generalized Anxiety Disorder-7; GAD-7), catastrophizing (Pain Catastrophizing Scale-Adapted; PCS-A), fear avoidance behavior (Fear Avoidance Behavior after Traumatic Brain Injury; FAB-TBI), and somatization (Patient Health Questionnaire-15; PHQ-15). Our primary outcome variables were self-reported symptom change during each symptom provocation test.

Results:

We found that current anxiety (B = 0.034; 95% CI = 0.003, 0.065), symptom catastrophizing (B = 0.013; 95% CI = 0.000, 0.026), fear avoidance behavior (B = 0.029; 95% CI = 0.008, 0.050), and somatization (B = 0.041; 95% CI = 0.007, 0.075) were associated with increased symptoms during the VOMS in univariate models adjusted for time postinjury but not in a multivariable model that included all covariates. The psychological variables of interest were not significantly related to symptom change during the BCBT or NIHTB-CB.

Conclusion:

Our findings suggest that symptom provocation test failure should be interpreted with caution because it might indicate psychological maladjustment rather than lingering brain injury or incomplete neurophysiological recovery.
Stroke Family Caregiver Life Changes From the COVID-19 Pandemic
Authors: Miller Elaine T. , Stacy Kelly E. , Bakas Tamilyn
Published: June 2022

BACKGROUND: Stroke family caregivers were already struggling with unmet needs and changes in their own lives from providing care. The COVID-19 pandemic added further stress and disruption to their lives. The purpose of this study was to describe life changes in 17 stroke family caregivers specifically resulting from the COVID-19 pandemic. METHODS: This study was conducted as a secondary data analysis from an ongoing randomized controlled clinical trial testing feasibility of the Telehealth Assessment and Skill-Building Kit (TASK III). Using a multimethod design, both quantitative and qualitative data were analyzed to determine caregiver life changes. Quantitative ratings regarding life changes were obtained using 17 items adapted specifically for COVID-19 from the Bakas Caregiving Outcomes Scale. Rigorous content analysis procedures for the qualitative data were guided by a start list of codes based on the 17 items, with additional themes possible. Representative quotes were selected based on author consensus. RESULTS: Findings revealed both negative and positive life changes from the COVID-19 pandemic. Negative life changes included such things as disrupted daily routines, limited access to healthcare providers and resources (eg, food, masks, hand sanitizers), reduced family and social contact and activities, decreased emotional well-being, and problems with performing caregiving activities for the survivor. Positive life changes were increased use of the Internet and videoconferencing, closer relationships with friends, and learning how to access needed resources in new ways. CONCLUSION: Stroke family caregivers experienced both negative and positive life changes specifically as a result of the COVID-19 pandemic. Responses further indicated that COVID-19 affected most caregivers in different ways and an individualized approach is needed in dealing with caregiver life changes.
Relationship between C-reactive protein/albumin ratio and dipper/nondipper pattern in normotensive individuals
Authors: Kayikçioğlu Hatice , Akbuğa Kürşat
Published: June 2022

Objective

Nondipper blood pressure pattern plays an important role in cardiovascular events even in normotensive individuals. The relationship between CRP (C-reactive protein)/albumin ratio (CAR), a valuable marker of inflammation and cardiovascular diseases, has been studied for a long time. We aimed to investigate the relationship between CAR and dipper/nondipper pattern in normotensive subjects.

Methods

A total of 78 dipper and 78 nondipper participants, based on ambulatory blood pressure monitoring (ABPM), were retrospectively included in our study. CAR and other parameters of all participants were collected from blood samples taken at the time of monitoring.

Results

CAR was significantly higher in the nondipper group than dipper group (P= 0.001). CAR was negatively and significantly correlated with nocturnal SBP fall ratio and nocturnal DBP fall ratio (P< 0.001). CRP/albumin ratio was found significantly and independently associated with the nondipper pattern (P= 0.002).

Conclusion

We found that normotensive individuals with nondipping pattern tend to have increased CAR. Increased inflammatory response could contribute to increase in the atherosclerotic risk in nondippers compared with dippers even in a normotensive profile.
Sex difference in blood pressure response to orthostatic stress: effects of transcutaneous electrical nerve stimulation
Authors: Gomes Erika Alvarenga Corrêa , Rodrigues Gabriel Dias , Oliveira André Luiz Musmanno Branco , Velasco Larissa Lírio , Soares Pedro Paulo da Silva , Nóbrega Antonio Claudio Lucas da , Toledo-Arruda Alessandra Choqueta
Published: June 2022

Objective

We investigated sex differences in blood pressure (BP) response to transcutaneous electrical nerve stimulation (TENS) during orthostatic stress (ORT).

Methods

Seventeen healthy young adults (males = 9; females = 8) underwent TENS or SHAM stimulus applied in the cervicothoracic region for 30 min in the supine position followed by 10 min in the orthostatic position. Electrocardiogram and BP were continuously recorded at rest and during ORT. Stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were calculated from the BP signal.

Results

Orthostatic challenge decreased BP similarly for both sexes during ORT, a deeper drop in CO and a slight increase in heart rate were found in women compared with men (P = 0.03 and 0.05, respectively). TENS evoked a pronounced fall in SBP in men compared with the SHAM condition (P < 0.05). TENS has no effect on SBP in women compared with the SHAM condition.

Conclusion

This finding suggests a possible modulatory effect by one cervicothoracic TENS session on sympathetic tonus in healthy men.
Regulatory T cells, damage-associated molecular patterns, and myeloid-derived suppressor cells in bronchoalveolar lavage fluid interlinked with chronic obstructive pulmonary disease severity
Authors: Brajer-Luftmann Beata , Kaczmarek Mariusz , Nowicka Agata , Stelmach-Mardas Marta , Wyrzykiewicz Magdalena , Yasar Senan , Piorunek Tomasz , Sikora Jan , Batura-Gabryel Halina
Published: June 2022

The role of regulatory T cells (Tregs), damage-associated molecular patterns (DAMPs), and myeloid-derived suppressor cells (MDSCs) in the mechanism of innate and adaptive immune responses in chronic obstructive pulmonary disease (COPD) is not well understood.

Evaluating the presence of Tregs in the bronchoalveolar lavage fluid (BALF) and peripheral blood in patients with COPD, and assessment of the relationship between Tregs, MDSCs, and DAMPs as factors activating innate and adaptive immune responses. Description of the association between immune and clinical parameters in COPD.

Thirty-one patients with COPD were enrolled. Clinical parameters (forced expiratory volume in one second [FEV1], forced vital capacity, total lung capacity [TLC], diffusion capacity of carbon monoxide, and B-BMI, O-obstruction, D-dyspnea, E-exercise [BODE]) were assessed. Tregs and MDSCs were investigated in the BALF and blood using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry. The levels of defensin (DEF2), galectin-1 (Gal-1), galectin-3 (Gal-3), galectin-9 (Gal-9), heat shock protein-27 (HSP27), and surfactant protein A were assessed via sandwich enzyme-linked immunosorbent assay.

The percentage of Tregs was significantly higher in the blood than in the BALF, in contrast to the mean fluorescence intensity of forkhead box P3 (FoxP3). Significant associations were observed between Tregs and HSP27 (r = 0.39), Gal-1 (r = 0.55), Gal-9 (r = −0.46), and MDSCs (r = −0.50), and between FoxP3 and Gal-1 (r = −0.42), Gal-3 (r = −0.39), and MDSCs (r = −0.43). Tregs and clinical parameters, including FEV1%pred (r = 0.39), residual volume (RV)%pred (r = −0.56), TLC%pred (r = −0.55), RV/TLC (r = −0.50), arterial oxygen saturation (r = −0.38), and arterial oxygen pressure (r = −0.39) were significantly correlated. FoxP3 was significantly interlinked with RV/TLC (r = −0.52), arterial oxygen pressure (r = 0.42), and BODE index (r = −0.57).

The interaction between innate and adaptive immune responses in patients with COPD was confirmed. The expression of Tregs in BALF may have prognostic value in patients with COPD. The conversion of immune responses to clinical parameters appears to be associated with disease severity.
Case report: pathological complete response in an IIIB non-small cell lung cancer patient after preoperative neoadjuvant nivolumab therapy combined with chemotherapy
Authors: Li Luzhen , Chen Ting , Lai Huiqin , Zhang Ao , Zhao Xianhui , Wu Jiaming , Hong Huisi , Wu Lexia , Lin Sihong , Wang Kexin , Zhang Huatang , Fang Cantu
Published: June 2022

Rationale:

For locally advanced non-small cell lung cancer (NSCLC), the neoadjuvant therapy strategy of preoperative nivolumab combined with chemotherapy has great potential, especially for locally advanced NSCLC which are initially unresectable. They may be cured after neoadjuvant immunotherapy, and this may become a new direction of treatment. We hope that this representative medical record and literature review can provide some assistance for clinicians using immune checkpoint inhibitors to treat lung cancer.

Patient concerns:

A 50-year-old male patient was admitted to Zhongshan Hospital of Traditional Chinese Medicine on April 27, 2020 due to “coughing for more than one month.”. The patient had nothing of note in either his medical history or that of his family, and no history of smoking.

Diagnosis:

The diagnosis was cT4N2M0IIIB stage right lower lung NSCLC with right hilar and mediastinal lymph node metastasis. The stage was inoperable stage IIIB NSCLC, but the patient had a strong willingness for doing surgery.

Interventions:

The patient received 3 rounds of the neoadjuvant nivolumab therapy combined with TP (paclitaxel plus cisplatin) regimen, on 5-14-21, 06-07-21 and 07-07-21.

Outcomes:

The tumor's area shrunk. Then the patient underwent thoracoscopic radical resection of the cancer in the right upper lung and postoperative pathology achieved pathological complete response (pCR)

Lessons:

In this case, combined with the wishes of the patient and the latest research results, we confirmed pCR by radical surgery after 3 rounds of the neoadjuvant nivolumab therapy combined with chemotherapy. This may be a modality to cure more lung cancer patients in the future.
Korean medicine registry of herbal medicine for weight loss
Authors: Ko Mi Mi , Kim Bo-Young , Son Mi Ju , Jegal Kyung Hwan , Chung Won-Seok , Kim Sungha
Published: June 2022

Introduction:

In South Korea, the prevalence of obesity has continuously increased over the last decade, and the burden of social and economic costs has also increased immensely. The purpose of this study is to investigate the clinical characteristics and current status of patients receiving herbal medicine (HM) treatment for weight loss in Korean medicine (KM) by constructing a multi-institutional prospective registry.

Methods and analysis:

This is a prospective, observational, multi-center registry, including patients visiting the KM clinics in South Korea for weight loss. This study will collaborate with 15 KM clinics and recruit patients into the registry between October 2021 and October 2022. The study population will include patients visiting the KM clinics for weight loss. A total of 1000 eligible patients visiting the KM clinics for weight loss who decide to undergo HM treatment will be enrolled in the registry. After enrollment, we will collect the individual characteristics of each patient, such as body mass index, body composition test, liver and kidney function tests, and information on prescribed HM. We will also record the adverse events at each visit.

Discussion:

This study is the first prospective, multicenter registry of HM for weight loss in KM clinics. The results of this registry may show the current status of patients who receive HM treatments for weight loss and provide evidence for reasonable decision-making on KM healthcare policy for obese patients in the future.
Outcomes of guideline-based medical therapy in patients with acute heart failure and reduced left ventricular ejection fraction
Authors: Jan Reem K. , Alsheikh-Ali Alawi , Mulla Arif Al , Sulaiman Kadhim , Panduranga Prashanth , Al-Mahmeed Wael , Bazargani Nooshin , Al-Suwaidi Jassim , Al-Jarallah Mohammed , Al-Motarreb Ahmed , Salam Amar , Al-Zakwani Ibrahim
Published: June 2022

This study aimed to report on the use, predictors and outcomes of guideline-based medical therapy (GBMT) in patients with acute heart failure (HF) with reduced ejection fraction of <40% (HFrEF), from seven countries in the Arabian Gulf.

Patients with acute HFrEF (N = 2680), aged 18 years or older, and hospitalized February–November 2012 were recruited and data were collected post discharge at 3 months (n = 2477) and 1 year (n = 2418). The use and doses of GBMT were evaluated as per European, American and Canadian HF guidelines. Analyses were performed using multivariate logistic regression. This study was registered at clinicaltrials.gov (NCT01467973).

The majority of patients were on dual (39%) and triple (39%) GBMT modalities, 14% received one GBMT medication, while 7.2% were not on any GBMT medications. On admission, 80% of patients were on renin-angiotensin system (RAS) blockers, 75% on b-blockers and 56% on mineralocorticoid receptor antagonists (MRAs), with a small proportion of these patients were taking target doses (RAS blockers 13%, b-blockers 7.3%, MRAs 14%). Patients taking triple GBMT were younger (P < .001), less likely to have comorbidities such as diabetes mellitus (P < .001) and CKD/dialysis (P < .001), less likely to receive in-hospital invasive treatments (P < .001), and more likely to be treated by a cardiologist (P < .001), than patients on a single medication. Patients taking triple GBMT showed significantly reduced all-cause mortality both at 3-months (P = .048), and at 12-months (P = .003), compared to patients taking no GBMT.

Triple GBMT prescribing and dosing in patients with HFrEF were suboptimal in the Arabian Gulf. Further studies are required to investigate GBMT utilization and dosing in the outpatient setting.
Enhanced recovery in elderly patients undergoing pancreatic resection
Authors: Scarsi Susanna , Martin David , Halkic Nermin , Demartines Nicolas , Roulin Didier
Published: June 2022

Enhanced recovery after surgery (ERAS) pathway for pancreas has demonstrated its value in clinical practice. However, there is a lack of specific evidence about its application in elderly patients. The aim of the present study was to assess the impact of age on compliance and postoperative outcomes. Patients ≥70 years old that underwent pancreatic resection within an ERAS pathway between 2012 and 2018 were included, and divided into three groups: 70–74, 75–79, and ≥80 years old. Compliance with ERAS items, length of stay, mortality, and complications were analyzed. 114 patients were included: 49, 37, and 28 patients aged 70–74, 75–79, and ≥80 years, respectively. Overall compliance to ERAS items between groups was not different (66%, 66%, and 62%, P = .201). No significant difference was observed in terms of median length of stay (14, 17, and 17 days, P = .717), overall complications (67%, 78%, and 71%, P = .529), major complications (26%, 32%, and 39%, P = .507), or mortality (0%, 3%, and 4%, P = .448) with increasing age. Application of an ERAS pathway is feasible in elderly patients with pancreatic resection. Increasing age was neither associated with poorer compliance nor worse postoperative outcomes.
Protocol and Outcome Evaluation of Comprehensive Outpatient Treatment of Adolescent Rumination Syndrome
Authors: Lamparyk Katherine , Stephens Taylor N.
Published: June 2022

Objectives:

Rumination syndrome (RS) is an increasingly recognized functional gastrointestinal condition with limited treatment research. Current treatment recommendations emphasize diaphragmatic breathing (DB), despite limited outcomes, and the most robust results have originated from inpatient treatment models. This paper described the protocol for Comprehensive Behavioral Treatment for Rumination Syndrome (CBT-R) utilized in an outpatient setting and evaluation of preliminary outcomes.

Methods:

The CBT-R protocol is described in detail, grounded in behavioral theory and phased treatment approach to symptom elimination. The treatment is evaluated via a retrospective case series design of pediatric patients (aged 8–18) with a primary diagnosis of RS treated in an outpatient setting by a pediatric psychologist.

Results:

Twenty-eight patients met inclusion criteria and are included in intent-to-treat analysis, with 23 patients evaluated for outcomes (47.8% female, Mage = 14.3; SD = 2.8). Sample included 17.4% with comorbid psychiatric diagnosis and 43.5% with comorbid medical diagnoses. Outcome results demonstrate improvement for a majority of patients (87.0%), with most demonstrating complete resolution of symptoms (73.9%). Treatment length varied significantly, ranging from 1 to 22 visits (M = 4.8, SD = 5.4) and was complicated by necessary admission or supplemental nutrition in 21.7% of patients. Psychological factors were related to poor treatment outcomes and longer treatment duration.

Conclusions:

CBT-R results in positive treatment outcomes for majority of patients, with most patients demonstrating complete resolution of symptoms, providing a superior outpatient treatment option for some pediatric patients. Sample characteristics challenge previous understanding of RS as female dominated and with high levels of psychiatric comorbidity.
Improved 30-Day Heart Failure Readmissions Following Implementation of an Advanced Cardiovascular Education (ACE) Academy
Authors: Oliver Beth , Travis Arlene , Hughes Ellen , Condrat Lindsay , Ullman Jennifer , Cohen Bevin , Cartwright Frances
Published: June 2022

Background:

Heart failure readmissions are common, though some are preventable through evidence-based management.

Local Problem:

Despite outperforming national benchmarks for 30-day readmissions, compliance with an evidence-based institutional heart failure management pathway was inconsistent. The purpose of this project was to reduce 30-day heart failure readmission rates through an educational intervention and an electronic health record (EHR) redesign.

Methods:

The cardiac services nursing leadership team conducted an education and documentation needs assessment to identify knowledge gaps and practical barriers to effective utilization of evidence-based interventions for heart failure management.

Interventions:

This intervention included an Advanced Cardiovascular Education (ACE) Academy and an EHR workflow redesign for clinical and supportive nursing staff.

Results:

The 30-day heart failure readmission rates reduced immediately following the intervention, and rates continued to decrease over a 3-year follow-up.

Conclusions:

Even among hospitals outperforming national benchmarks, 30-day heart failure readmissions can be reduced and sustained with enhanced education and EHR redesign.
SARS-CoV–Related Pandemic Outbreaks and Mental Disorder Risk
Authors: Deng Xiangling , He Mengyang , Zhang Jinhe , Huang Jinchang , Luo Minjing , Zhang Zhixin , Niu Wenquan
Published: June 2022

This study aimed to quantify the association between exposure to pandemic outbreaks and psychological health via a comprehensive meta-analysis. Literature retrieval, study selection, and data extraction were completed independently and in duplicate. Effect-size estimates were expressed as odds ratio (OR) with 95% confidence interval (CI). Data from 22 articles, involving 40,900 persons, were meta-analyzed. Overall analyses revealed a significant association of exposing to SARS-CoV–related pandemics with human mental health (OR, 1.32; 95% CI, 1.24–1.40; p < 0.001). Subgroup analyses showed that anxiety (OR, 1.37; 95% CI, 1.19–1.58; p < 0.001), depression (OR, 1.28; 95% CI, 1.15–1.42; p < 0.001), posttraumatic stress (OR, 1.36; 95% CI, 1.17–1.58; p < 0.001), and psychological distress (OR, 1.25; 95% CI, 1.11–1.40; p < 0.001) were all obviously related to pandemic diseases. In the context of infectious disease outbreaks, the mental health of general populations is clearly vulnerable. Therefore, all of us, especially health care workers, need special attention and psychological counseling to overcome pandemic together.
Clinical Course in Patients With Melancholic and Nonmelancholic Bipolar Depression
Authors: Martino Diego J. , Valerio Marina P. , Lomastro Julieta , Igoa Ana
Published: June 2022

The aim of the current study was to compare the longitudinal clinical course of patients with a history of melancholic and nonmelancholic bipolar depression. Seventy-seven euthymic outpatients with bipolar disorder were categorized as melancholic or nonmelancholic through the clinician-rated Sydney Melancholia Prototype Index. Clinical course was assessed for a period longer than 48 months by time spent ill, density of affective episodes, severity and duration of depressive episodes, and time to depressive recurrence. The mean follow-up time was 69.05 months. Patients with melancholic depressions had more severe and longer depressive episodes during follow-up, whereas patients with nonmelancholic depressions had a shorter time to depressive recurrence and more subsyndromal depressive symptoms and affective instability. These findings highlight the heterogeneity inherent to the current construct of bipolar depression and position melancholia as an interesting target for comparison with nonmelancholic depressions in other external validators in the field of bipolar disorder.
New Screening Strategy Combining Anal Papanicolaou and Human Papillomavirus Tests for Human Papillomavirus–Related Anal Cancer: A Prospective, Single-Center Study
Authors: Pisano Luigi , Grandi Vieri , Tiradritti Luana , Zuccati Giuliano , Caminati Filippo , Giani Iacopo , Bisanzi Simonetta , Matucci Marzia , Carozzi Francesca , Pimpinelli Nicola , Elbetti Claudio
Published: June 2022

Background

The objective of this study was to evaluate the performance of a combined approach of liquid-based anal cytology and human papillomavirus (HPV) testing in predicting patients who should undergo high-resolution anoscopy for the early detection of anal cancer and anal intraepithelial neoplasia (AIN)-2+.

Methods

We conducted a prospective single-center quality improvement study. We consecutively enrolled men who had sex with men (MSM) attending our sexually transmitted disease clinic to undergo anal Papanicolaou (Pap) and HPV tests. All patients with an abnormal anal Pap test result and/or positive HPV test result underwent high-resolution anoscopy.

Results

We enrolled 217 MSM, 80 HIV-positive patients, and 137 HIV-negative patients. Cytology showed a sensitivity of 100%, a specificity of 64.1%, an accuracy of 66.7%, a positive predictive value (PPV) of 15.7%, and a negative predictive value (NPV) of 100% for the detection of AIN-2+. The high-risk (HR)-HPV test showed sensitivity, specificity, accuracy, PPV, and NPV of 100%, 36.4%, 40%, 9.4%, and 100%, respectively. The combination of abnormal cytology with identification of infection by at least 1 HR-HPV strain on the HPV test had a sensitivity of 100%, a specificity of 73%, an accuracy of 74.6%, a PPV of 19.1%, and an NPV of 100%.

Conclusion

Anal HR-HPV testing, complementary to cytology, improves the diagnostic accuracy of screening for anal cancer.
“Malignant Mesenchymoma” Revisited
Authors: Yu Sanhong , Hornick Jason L.
Published: June 2022

Leiomyosarcoma (LMS) is the most common sarcoma in adults. Rarely, LMS dedifferentiates into an undifferentiated sarcoma. Very few cases of LMS with heterologous osteosarcomatous differentiation (OS) have been reported. The purpose of this study was to evaluate the clinicopathologic features of LMS with OS. Of 5570 LMS cases diagnosed from 2006 to 2022, 15 cases (0.2%) of LMS with OS were identified, affecting 13 females and 2 males; ages ranged from 32 to 66 years (median: 53 y). Ten tumors arose in the uterus, 2 in the retroperitoneum, and 1 each in the mesentery, mediastinum, and rectum. Primary tumors ranged from 7 to 20 cm (mean: 16 cm). The LMS components showed conventional spindle cell morphology in most cases; 3 cases showed marked pleomorphism; 3 cases contained an epithelioid component; and 1 case showed myxoid features. In 5 cases OS was identified in the primary tumor, whereas in 10 cases OS was first detected in metastases. One metastatic and 2 primary LMS showed both OS and chondrosarcomatous differentiation. Prominent osteoclastic giant cells were seen in the OS components in 11 cases. Mitotic activity ranged from 17 to 61/10 HPF with tumor necrosis in 10 cases. Twelve patients developed metastases; sites included lungs, diaphragm, kidney, adrenal glands, colon, small intestine, liver, bone, and pancreas. At last follow-up, 8 patients had died of disease, and 4 patients were alive with metastases. The interval between OS and death ranged from 3 weeks to 18 months (median: 6.5 mo). Development of OS in LMS is exceptionally rare. This form of heterologous differentiation may occur in both primary tumors and metastases. LMS with OS is highly aggressive with poor outcomes. Awareness of this phenomenon is important to avoid misdiagnosis as osteosarcoma.