Osteoprotegerin Expression in Liver is Induced by IL13 through TGFβ

Cell Physiol Biochem. 2022 Jan 22;56(1):28-38. doi: 10.33594/000000492.


BACKGROUND/AIMS: Osteoprotegerin (OPG) is a profibrotic mediator produced by myofibro-blasts under influence of transforming growth factor β (TGFβ). Its expression in experimental models of liver fibrosis correlates well with disease severity and treatment responses. The regulation of OPG in liver tissue is largely unknown and we therefore set out to elucidate which growth factors/interleukins associated with fibrosis induce OPG and through which pathways.

METHODS: Precision-cut liver slices of wild type and STAT6-deficient mice and 3T3 fibroblasts were used to investigate the effects of TGFβ, interleukin (IL) 13 (IL13), IL1β, and platelet-derived growth factor BB (PDGF-BB) on expression of OPG. OPG protein was measure by ELISA, whereas OPG mRNA and expression of other relevant genes was measured by qPCR.

RESULTS: In addition to TGFβ, only IL13 and not PDGF-BB or IL1β could induce OPG expression in 3T3 fibroblasts and liver slices. This IL13-dependent induction was not shown in liver slices of STAT6-deficient mice and when wild type slices were cotreated with TGFβ receptor 1 kinase inhibitor galunisertib, STAT6 inhibitor AS1517499, or AP1 inhibitor T5224. This suggests that the OPG-inducing effect of IL13 is mediated through IL13 receptor α1-activation and subsequent STAT6-dependent upregulation of IL13 receptor α2, which in turn activates AP1 and induces production of TGFβ and subsequent production of OPG.

CONCLUSION: We have shown that IL13 induces OPG release by liver tissue through a TGFβ-dependent pathway involving both the α1 and the α2 receptor of IL13 and transcription factors STAT6 and AP1. OPG may therefore be a novel target for the treatment liver fibrosis as it is mechanistically linked to two important regulators of fibrosis in liver, namely IL13 and TGFβ1.

PMID:35060690 | DOI:10.33594/000000492

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Diagnostic Testing for Sepsis: A Systematic Review of Economic Evaluations

Antibiotics (Basel). 2021 Dec 27;11(1):27. doi: 10.3390/antibiotics11010027.


INTRODUCTION: Sepsis is a serious and expensive healthcare problem, when caused by a multidrug-resistant (MDR) bacteria mortality and costs increase. A reduction in the time until the start of treatment improves clinical results. The objective is to perform a systematic review of economic evaluations to analyze the cost-effectiveness of diagnostic methods in sepsis and to draw lessons on the methods used to incorporate antimicrobial resistance (AMR) in these studies.

MATERIAL AND METHODS: the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and the Consolidated Health Economic Evaluation Reporting standards (CHEERS) checklist was used to extract the information from the texts.

RESULTS: A total of 16 articles were found. A decision model was performed in 14. We found two ways to handle resistance while modelling: the test could identify infections caused by a resistant pathogen or resistance-related inputs, or outcomes were included (the incidence of AMR in sepsis patients, antibiotic use, and infection caused by resistant bacterial pathogens).

CONCLUSION: Using a diagnostic technique to detect sepsis early on is more cost-effective than standard care. Setting a direct relationship between the implementation of a testing strategy and the reduction of AMR cases, we made several assumptions about the efficacy of antibiotics and the length-of-stay of patients.

PMID:35052904 | DOI:10.3390/antibiotics11010027

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Spatial and Temporal Gene Function Studies in Rodents: Towards Gene-Based Therapies for Autism Spectrum Disorder

Genes (Basel). 2021 Dec 23;13(1):28. doi: 10.3390/genes13010028.


Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is characterized by differences in social interaction, repetitive behaviors, restricted interests, and sensory differences beginning early in life. Especially sensory symptoms are highly correlated with the severity of other behavioral differences. ASD is a highly heterogeneous condition on multiple levels, including clinical presentation, genetics, and developmental trajectories. Over a thousand genes have been implicated in ASD. This has facilitated the generation of more than two hundred genetic mouse models that are contributing to understanding the biological underpinnings of ASD. Since the first symptoms already arise during early life, it is especially important to identify both spatial and temporal gene functions in relation to the ASD phenotype. To further decompose the heterogeneity, ASD-related genes can be divided into different subgroups based on common functions, such as genes involved in synaptic function. Furthermore, finding common biological processes that are modulated by this subgroup of genes is essential for possible patient stratification and the development of personalized early treatments. Here, we review the current knowledge on behavioral rodent models of synaptic dysfunction by focusing on behavioral phenotypes, spatial and temporal gene function, and molecular targets that could lead to new targeted gene-based therapy.

PMID:35052369 | DOI:10.3390/genes13010028

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Process Evaluation of Lumbar Interbody Fusion Surgeries in Five Dutch Hospitals: A Qualitative Analysis

Medicina (Kaunas). 2022 Jan 9;58(1):99. doi: 10.3390/medicina58010099.


Background and Objectives: Only limited qualitative research concerning instrumented spine surgeries has been published, despite the increasing number of these surgeries and the evident importance of qualitative analysis of the processes surrounding these complex interventions. Current qualitative research is mainly limited to the experiences, emotions and expectations of patients. Insight into the full process, including experiences from the perspective of informal caregivers and healthcare professionals, remains scarce. Materials and Methods: Data were gathered by means of semi-structured face-to-face interviews. In total, there were 27 participants, including 11 patients, 7 informal caregivers and 9 healthcare professionals. The interview process was audiotaped, and each interview was transcribed verbatim. To systematically analyse the gathered data, software for qualitative analysis (NVivo) was used. After immersion in the raw data of transcripts and field notes, a list of broad categories for organising the data into meaningful clusters for analysis was developed. All interviews were coded by the first author, and 25% was independently assessed by the second author. Results: The results of our study describe several promoting and limiting factors concerning the process of lumbar fusion surgery from the perspective of patients, informal caregivers and healthcare providers. The most frequently mentioned promoting factors were: information and opportunities to ask questions during consultations; multidisciplinary consultations; good communication and guidance during hospitalization; and follow-up appointments. The most frequently mentioned limiting factors were: lack of educational material; lack of guidance and communication prior to, during and after hospitalisation. Conclusion: Overall, participants were satisfied with the current healthcare-process in lumbar fusion surgery. However, we found that lack of educational material and guidance during the process led to insecurity about complaints, surgery and recovery. To improve the process of lumbar interbody fusion and to increase patient satisfaction, healthcare providers should focus on guiding and educating patients and informal caregivers about the pre-operative trajectory, the surgery and the recovery. From the healthcare providers’ perspective, the process could be improved by multidisciplinary consultations and a dedicated spine team in the operation room. Although this study focusses on lumbar fusion surgery, results could be translated to other fields of spine surgery and surgery in general.

PMID:35056407 | DOI:10.3390/medicina58010099

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Galectin-9 Triggers Neutrophil-Mediated Anticancer Immunity

Biomedicines. 2021 Dec 29;10(1):66. doi: 10.3390/biomedicines10010066.


In earlier studies, galectin-9 (Gal-9) was identified as a multifaceted player in both adaptive and innate immunity. Further, Gal-9 had direct cytotoxic and tumor-selective activity towards cancer cell lines of various origins. In the current study, we identified that treatment with Gal-9 triggered pronounced membrane alterations in cancer cells. Specifically, phosphatidyl serine (PS) was rapidly externalized, and the anti-phagocytic regulator, CD47, was downregulated within minutes. In line with this, treatment of mixed neutrophil/tumor cell cultures with Gal-9 triggered trogocytosis and augmented antibody-dependent cellular phagocytosis of cancer cells. Interestingly, this pro-trogocytic effect was also due to the Gal-9-mediated activation of neutrophils with upregulation of adhesion markers and mobilization of gelatinase, secretory, and specific granules. These activation events were accompanied by a decrease in cancer cell adhesion in mixed cultures of leukocytes and cancer cells. Further, prominent cytotoxicity was detected when leukocytes were mixed with pre-adhered cancer cells, which was abrogated when neutrophils were depleted. Taken together, Gal-9 treatment potently activated neutrophil-mediated anticancer immunity, resulting in the elimination of epithelial cancer cells.

PMID:35052746 | DOI:10.3390/biomedicines10010066

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Simultaneous Exposure of Different Nanoparticles Influences Cell Uptake

Pharmaceutics. 2022 Jan 6;14(1):136. doi: 10.3390/pharmaceutics14010136.


Drug delivery using nano-sized carriers holds tremendous potential for curing a range of diseases. The internalisation of nanoparticles by cells, however, remains poorly understood, restricting the possibility for optimising entrance into target cells, avoiding off-target cells and evading clearance. The majority of nanoparticle cell uptake studies have been performed in the presence of only the particle of interest; here, we instead report measurements of uptake when the cells are exposed to two different types of nanoparticles at the same time. We used carboxylated polystyrene nanoparticles of two different sizes as a model system and exposed them to HeLa cells in the presence of a biomolecular corona. Using flow cytometry, we quantify the uptake at both average and individual cell level. Consistent with previous literature, we show that uptake of the larger particles is impeded in the presence of competing smaller particles and, conversely, that uptake of the smaller particles is promoted by competing larger particles. While the mechanism(s) underlying these observations remain(s) undetermined, we are partly able to restrain the likely possibilities. In the future, these effects could conceivably be used to enhance uptake of nano-sized particles used for drug delivery, by administering two different types of particles at the same time.

PMID:35057032 | DOI:10.3390/pharmaceutics14010136

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Ceftriaxone for the Treatment of Chronic Bacterial Prostatitis: A Case Series and Literature Review

Antibiotics (Basel). 2022 Jan 11;11(1):83. doi: 10.3390/antibiotics11010083.


Chronic bacterial prostatitis is increasingly difficult to treat due to rising antimicrobial resistance limiting oral treatment options. In this case series, 11 men with CBP (including patients with urological comorbidities) due to multi-resistant E. coli were treated with once-daily ceftriaxone intravenously for 6 weeks. Nine patients were clinically cured at 3 months follow up. No early withdrawal of medication due to side effects occurred. A literature review was conducted to describe the prostate pharmacokinetics of ceftriaxone and its use in prostatic infection. In conclusion, ceftriaxone can be considered an appropriate treatment of chronic bacterial prostatitis.

PMID:35052960 | DOI:10.3390/antibiotics11010083

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Receptor Specificity Engineering of TNF Superfamily Ligands

Pharmaceutics. 2022 Jan 13;14(1):181. doi: 10.3390/pharmaceutics14010181.


The tumor necrosis factor (TNF) ligand family has nine ligands that show promiscuity in binding multiple receptors. As different receptors transduce into diverse pathways, the study on the functional role of natural ligands is very complex. In this review, we discuss the TNF ligands engineering for receptor specificity and summarize the performance of the ligand variants in vivo and in vitro. Those variants have an increased binding affinity to specific receptors to enhance the cell signal conduction and have reduced side effects due to a lowered binding to untargeted receptors. Refining receptor specificity is a promising research strategy for improving the application of multi-receptor ligands. Further, the settled variants also provide experimental guidance for engineering receptor specificity on other proteins with multiple receptors.

PMID:35057080 | DOI:10.3390/pharmaceutics14010181

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The Implementation of TNFRSF Co-Stimulatory Domains in CAR-T Cells for Optimal Functional Activity

Cancers (Basel). 2022 Jan 8;14(2):299. doi: 10.3390/cancers14020299.


The Tumor Necrosis Factor Receptor Superfamily (TNFRSF) is a large and important immunoregulatory family that provides crucial co-stimulatory signals to many if not all immune effector cells. Each co-stimulatory TNFRSF member has a distinct expression profile and a unique functional impact on various types of cells and at different stages of the immune response. Correspondingly, exploiting TNFRSF-mediated signaling for cancer immunotherapy has been a major field of interest, with various therapeutic TNFRSF-exploiting anti-cancer approaches such as 4-1BB and CD27 agonistic antibodies being evaluated (pre)clinically. A further application of TNFRSF signaling is the incorporation of the intracellular co-stimulatory domain of a TNFRSF into so-called Chimeric Antigen Receptor (CAR) constructs for CAR-T cell therapy, the most prominent example of which is the 4-1BB co-stimulatory domain included in the clinically approved product Kymriah. In fact, CAR-T cell function can be clearly influenced by the unique co-stimulatory features of members of the TNFRSF. Here, we review a select group of TNFRSF members (4-1BB, OX40, CD27, CD40, HVEM, and GITR) that have gained prominence as co-stimulatory domains in CAR-T cell therapy and illustrate the unique features that each confers to CAR-T cells.

PMID:35053463 | DOI:10.3390/cancers14020299

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Drug Targeting and Nanomedicine: Lessons Learned from Liver Targeting and Opportunities for Drug Innovation

Pharmaceutics. 2022 Jan 17;14(1):217. doi: 10.3390/pharmaceutics14010217.


Drug targeting and nanomedicine are different strategies for improving the delivery of drugs to their target. Several antibodies, immuno-drug conjugates and nanomedicines are already approved and used in clinics, demonstrating the potential of such approaches, including the recent examples of the DNA- and RNA-based vaccines against COVID-19 infections. Nevertheless, targeting remains a major challenge in drug delivery and different aspects of how these objects are processed at organism and cell level still remain unclear, hampering the further development of efficient targeted drugs. In this review, we compare properties and advantages of smaller targeted drug constructs on the one hand, and larger nanomedicines carrying higher drug payload on the other hand. With examples from ongoing research in our Department and experiences from drug delivery to liver fibrosis, we illustrate opportunities in drug targeting and nanomedicine and current challenges that the field needs to address in order to further improve their success.

PMID:35057111 | DOI:10.3390/pharmaceutics14010217

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Risk for Pelvic Metastasis and Role of Pelvic Lymphadenectomy in Node-Positive Vulvar Cancer-Results from the AGO-VOP.2 QS Vulva Study

Cancers (Basel). 2022 Jan 14;14(2):418. doi: 10.3390/cancers14020418.


The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b.

PMID:35053582 | DOI:10.3390/cancers14020418

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Mild traumatic brain injury in elderly patients receiving direct oral anticoagulants: A systematic review and meta-analysis

J Neurotrauma. 2022 Jan 21. doi: 10.1089/neu.2021.0435. Online ahead of print.


To conduct a systematic review and meta-analysis of studies reporting on the risk of traumatic intracranial hemorrhage (tICH), the course of tICH, its treatment and mortality rates in elderly mild traumatic brain injury (mTBI) patients using direct oral anticoagulants (DOACs). We consulted PubMed and Embase for relevant cohort and case-control studies with a control group. Two authors independently selected studies, assessed methodological quality and extracted outcome data. Estimates were pooled with the Mantel-Haenszel random-effects method. We identified 16 articles comprising 3671 elderly mTBI patients, 1344 of which were using DOACs. The use of DOACs was associated with a reduced risk of tICH compared to the use of vitamin K antagonists (VKAs) (Odds Ratio (OR): 0.44, 95% confidence interval (CI): 0.29-0.65, I2=22%) and a similar risk compared to the use of antiplatelet therapy (APT) (OR: 0.98, 95% CI: 0.39-2.44, I2=0%). Reversal agent use and neurosurgical intervention rate were lower in patients using DOACs compared to patients using VKAs (OR: 0.10, 95% CI: 0.06-0.16, I2=0% and OR: 0.37, 95% CI: 0.21-0.67, I2=0% respectively). There was no significant difference in neurosurgical intervention rate between patients that used DOACs versus patients that used APT (OR: 0.58, 95% CI: 0.15-2.21, I2=41%) or no antithrombotic therapy (ATT) (OR: 0.76 95%, CI: 0.20-2.86, I2=23%). ICH progression, risk of delayed ICH (dICH) and traumatic brain injury (TBI)-related in hospital mortality was comparable among treatment groups. The present study indicates that elderly patients using DOACs have a lower risk of adverse outcome compared to patients using VKAs and a similar risk compared to patients using APT after mTBI.

PMID:35057639 | DOI:10.1089/neu.2021.0435

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Health Literacy and Change in Health-Related Quality of Life in Dialysed Patients

Int J Environ Res Public Health. 2022 Jan 6;19(2):620. doi: 10.3390/ijerph19020620.


Health-related quality of life (HRQoL) is likely to deteriorate with the progression of chronic kidney disease (CKD). This change may be worsened by low health literacy (HL). We performed a longitudinal study at over 20 dialysis clinics in Slovakia (n = 413; mean age = 64.8 years; males = 58.4%). We assessed the association of three HL groups with a change in HRQoL over two years using binary logistic regression adjusted for type of vascular access, dialysis effectiveness, comorbidity, age and gender. We found that patients with low HL had poorer HRQoL at baseline in comparison to high-HL patients. We did not find significant associations of lower HL with the deterioration of mental or physical HRQoL after two years. In the adjusted model, patients with lower HL were not more likely to have deteriorated physical (low-HL patients: odds ratio/95% confidence interval: 0.99/0.53-1.84; moderate-HL patients: 0.97/0.55-1.73) or mental HRQoL (low-HL patients: 1.00/0.53-1.87; moderate-HL patients: 0.95/0.53-1.70) in comparison to high-HL patients. The HRQoL of lower-HL patients is worse at baseline but develops similarly to that of high-HL patients during dialysis treatment. Their relative HRQoL, thus, does not worsen further, but it does not improve either. Tailoring care to their needs may help to decrease the burden of low HL in dialysed patients.

PMID:35055440 | DOI:10.3390/ijerph19020620

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Spatiotemporal prediction of vancomycin-resistant Enterococcus colonisation

BMC Infect Dis. 2022 Jan 20;22(1):67. doi: 10.1186/s12879-022-07043-9.


BACKGROUND: Vancomycin-resistant enterococci (VRE) is the cause of severe patient health and monetary burdens. Antibiotic use is a confounding effect to predict VRE in patients, but the antibiotic use of patients who may have frequented the same ward as the patient in question is often neglected. This study investigates how patient movements between hospital wards and their antibiotic use can explain the colonisation of patients with VRE.

METHODS: Intrahospital patient movements, antibiotic use and PCR screening data were used from a hospital in the Netherlands. The PageRank algorithm was used to calculate two daily centrality measures based on the spatiotemporal graph to summarise the flow of patients and antibiotics at the ward level. A decision tree model was used to determine a simple set of rules to estimate the daily probability of patient VRE colonisation for each hospital ward. The model performance was improved using a random forest model and compared using 30% test sample.

RESULTS: Centrality covariates summarising the flow of patients and their antibiotic use between hospital wards can be used to predict the daily colonisation of VRE at the hospital ward level. The decision tree model produced a simple set of rules that can be used to determine the daily probability of patient VRE colonisation for each hospital ward. An acceptable area under the ROC curve (AUC) of 0.755 was achieved using the decision tree model and an excellent AUC of 0.883 by the random forest model on the test set. These results confirms that the random forest model performs better than a single decision tree for all levels of model sensitivity and specificity on data not used to estimate the models.

CONCLUSION: This study showed how the movements of patients inside hospitals and their use of antibiotics could predict the colonisation of patients with VRE at the ward level. Two daily centrality measures were proposed to summarise the flow of patients and antibiotics at the ward level. An early warning system for VRE can be developed to test and further develop infection prevention plans and outbreak strategies using these results.

PMID:35057734 | DOI:10.1186/s12879-022-07043-9

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A Multinational Longitudinal Study Incorporating Intensive Methods to Examine Caregiver Experiences in the Context of Chronic Health Conditions: Protocol of the ENTWINE-iCohort

Int J Environ Res Public Health. 2022 Jan 12;19(2):821. doi: 10.3390/ijerph19020821.


Informal caregivers are those who provide unpaid care to a relative or friend with a chronic illness, disability or other long-lasting health or care need. Providing informal care in the context of chronic health conditions presents a significant global challenge. Examination of the determinants of informal caregivers’ behaviour, especially in terms of motivations and willingness to provide/receive care, is crucial to understanding the nature of caregiver and care recipient experiences. A large group of international researchers have co-operated to execute the ENTWINE iCohort-a multinational, transdisciplinary, longitudinal study incorporating intensive methods to examine caregiver experiences in the context of chronic health conditions. The aim of ENTWINE-iCohort is to investigate the broad spectrum of factors, i.e., cultural, personal, geographical, relational, psychological, and economic that may affect motivations, willingness to provide or receive care, among diverse groups of informal caregivers and their care recipients, in different countries that have different care systems. Study questionnaires will be disseminated on-line in nine countries: Germany, Greece, Ireland, Italy, Israel, the Netherlands, Poland, Sweden, and the UK. Cross-sectional and longitudinal multivariate analysis, including intensive longitudinal and dyadic data analysis will be applied to examine the relative contribution of the above factors to caregiver or care recipient wellbeing.

PMID:35055644 | DOI:10.3390/ijerph19020821

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Influence of the interventionist’s experience on outcomes of endovascular thrombectomy in acute ischemic stroke: results from the MR CLEAN Registry

J Neurointerv Surg. 2022 Jan 20:neurintsurg-2021-018295. doi: 10.1136/neurintsurg-2021-018295. Online ahead of print.


BACKGROUND: The relationship between the interventionist’s experience and outcomes of endovascular thrombectomy (EVT) for acute ischemic stroke of the anterior circulation, is unclear.

OBJECTIVE: To assess the effect of the interventionist’s level of experience on clinical, imaging, and workflow outcomes. Secondly, to determine which of the three experience definitions is most strongly associated with these outcome measures.

METHODS: We analysed data from 2700 patients, included in the MR CLEAN Registry. We defined interventionist’s experience as the number of procedures performed in the year preceding the intervention (EXPfreq), total number of procedures performed (EXPno), and years of experience (EXPyears). Our outcomes were the baseline-adjusted National Institutes of Health Stroke Scale (NIHSS) score at 24-48 hours post-EVT, recanalization (extended Thrombolysis in Cerebral Infarction (eTICI) score ≥2B), and procedural duration. We used multilevel regression models with interventionists as random intercept. For EXPfreq and EXPno results were expressed per 10 procedures.

RESULTS: Increased EXPfreq was associated with lower 24-48 hour NIHSS scores (adjusted (a)β:-0.46, 95% CI -0.70 to -0.21). EXPno and EXPyears were not associated with short-term neurological outcomes. Increased EXPfreq and EXPno were both associated with recanalization (aOR=1.20, 95% CI 1.11 to 1.31 and aOR=1.08, 95% CI 1.04 to 1.12, respectively), and increased EXPfreq, EXPno, and EXPyears were all associated with shorter procedure times (aβ:-3.08, 95% CI-4.32 to -1.84; aβ:-1.34, 95% CI-1.84 to -0.85; and aβ:-0.79, 95% CI-1.45 to -0.13, respectively).

CONCLUSIONS: Higher levels of interventionist’s experience are associated with better outcomes after EVT, in particular when experience is defined as the number of patients treated in the preceding year. Every 20 procedures more per year is associated with approximately one NIHSS score point decrease, an increased probability for recanalization (aOR=1.44), and a 6-minute shorter procedure time.

PMID:35058316 | DOI:10.1136/neurintsurg-2021-018295

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Growing up with a Chronically Ill Family Member-The Impact on and Support Needs of Young Adult Carers: A Scoping Review

Int J Environ Res Public Health. 2022 Jan 13;19(2):855. doi: 10.3390/ijerph19020855.


This scoping review provides an overview of the impact of growing up with a chronically ill family member on young adults (18-25 years old), and their specific needs. Young adults represent an important life stage involving a transition to adulthood, during which individuals’ family situations can affect their future. We searched relevant studies following the guideline of Arskey and O’Mailley’s methodological framework and the PRISMA statement guidelines for scoping reviews in PubMed, PsychInfo and reference lists to identify articles for inclusion. Studies from 2005 to 2020 were included in this review. Of the 12 studies, six qualitative studies, five quantitative studies and one mixed method study were included. Eight studies discussed the impact, including consequences at a physical and mental level, at their personal development and future perspectives, but also positive effects, such as being capable of organizing their lives. Four studies discussed the needs of young adult carers, including emotional needs, support needs with regard to stimulating autonomy (arising from internal conflicts) and developing their own identity, and the concerned attitude of involved professionals. An unambiguous definition of the target group and further well-designed research are needed to improve clarity about the role of support, so that future professionals can adequately address the needs and wishes of young adults who grow up with an ill family member.

PMID:35055678 | DOI:10.3390/ijerph19020855

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Barriers and facilitators for systematically registering adverse drug reactions in electronic health records: a qualitative study with Dutch healthcare professionals

Expert Opin Drug Saf. 2022 Jan 21. doi: 10.1080/14740338.2022.2020756. Online ahead of print.


BACKGROUND: Systematically registering ADRs in electronic health records (EHRs) likely contribute to patient safety as it enables the exchange of drug safety data. Currently, ADRs registrations by healthcare professionals (HCPs) is suboptimal. This study aimed to identify barriers and facilitators perceived by HCPs to register ADRs systematically in EHRs.

RESEARCH DESIGN AND METHODS: A qualitative study with individual interviews was conducted among specialist physicians and hospital pharmacists from 10 different Dutch hospitals. A semi-structured interview guide was used to identify experienced barriers and facilitators for systematically registering ADRs. Data was analysed following thematic analysis. Themes within barriers and facilitators were aligned with the Capability-Opportunity-Motivation-Behaviour (COM-B) framework.

RESULTS: In total, 16 HCPs were interviewed. Identified barriers were: lack of knowledge to recognize ADRs, time constraints, inadequate IT system, lack of support, stuck in routine, and not recognizing the importance of registering ADRs. Identified facilitators were: enhanced knowledge and awareness of ADRs, functional IT systems, expanding accountability for registration, and motivation towards registering.

CONCLUSIONS: Barriers and facilitators for registering spanned all aspects of the COM-B model and occurred in individual, social and environmental domains. Addressing these aspects could improve the registration of ADRs and may contribute to patient safety.

PMID:35060443 | DOI:10.1080/14740338.2022.2020756

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Sex differences in proteomic correlates of coronary microvascular dysfunction among patients with heart failure and preserved ejection fraction

Eur J Heart Fail. 2022 Jan 21. doi: 10.1002/ejhf.2435. Online ahead of print.


BACKGROUND: Little information is available on sex differences in coronary microvascular dysfunction (CMD) in heart failure with preserved ejection fraction (HFpEF). We investigated sex-specific proteomic profiles associated with CMD in patients with HFpEF.

METHODS: Using the prospective multinational PROMIS-HFpEF study (Prevalence of Microvascular Dysfunction in HFpEF; n = 182; 54.6% women), we compared clinical and biomarker correlates of CMD (defined as coronary flow reserve [CFR] <2.5) between men and women with HFpEF. We used lasso penalised regression to analyse 242 biomarkers from high-throughput proximity extension assays, adjusting for age, body mass index, creatinine, smoking and study site.

RESULTS: The prevalence of CMD was similarly high in men and women with HFpEF (77 vs. 70%; p = 0.27). Proteomic correlates of CFR differed by sex, with 10 vs. 16 non-overlapping biomarkers independently associated with CFR in men vs. women respectively. In men, proteomic correlates of CFR included chemokine ligand 20, brain natriuretic peptide, proteinase 3, transglutaminase 2, pregnancy-associated plasma protein A and tumor necrosis factor receptor superfamily member 14. Among women, the strongest proteomic correlates with CFR were insulin-like growth factor-binding protein 1, phage shock protein D, CUB domain-containing protein 1, prostasin, decorin, FMS-like tyrosine kinase 3, ligandgrowth/differentiation factor 15, spondin-1, delta/notch-like EGF-related receptor and tumor necrosis factor receptor superfamily member 13B. Pathway analyses suggested that CMD was related to the inflammation-mediated chemokine and cytokine signalling pathway among men with HFpEF, and the P13-kinase and TGF-beta signalling pathway among women with HFpEF.

CONCLUSION: While the prevalence of CMD among men and women with HFpEF is similar, the drivers of microvascular dysfunction may differ by sex. The current inflammatory paradigm of CMD in HFpEF potentially predominates in men, while derangement in ventricular remodeling and fibrosis may play a more important role in women. This article is protected by copyright. All rights reserved.

PMID:35060248 | DOI:10.1002/ejhf.2435

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How does the Untire App alleviate Cancer-Related Fatigue?A Longitudinal Mediation Analysis

Psychooncology. 2022 Jan 20. doi: 10.1002/pon.5886. Online ahead of print.


OBJECTIVE: A waiting-list randomized controlled trial (RCT) supported the effectiveness of the multimodal Untire app in reducing cancer-related fatigue (CRF) in cancer patients and survivors. However, little is known about the causal mechanisms of different app components through which the intervention effect was achieved. We aim to examine whether specifically targeted factors (i.e., fatigue catastrophizing, depression, mindfulness, sleep, and physical activity) mediated the intervention effects of the Untire app on fatigue outcomes.

METHODS: 799 persons with CRF were randomized (2:1) into intervention (n=519) and waiting-list control (n=280) groups. Self-report data on the primary outcome fatigue severity and interference and the abovementioned potential mediators were collected at baseline and 12-weeks. Participants who completed the 12-week assessment were included in the analyses (intervention=159; control=176). We performed longitudinal multi-categorical multiple mediation analysis using PROCESS macro to examine whether the potential mediators explained the overall intervention effects.

RESULTS: Improvements in fatigue catastrophizing (bootstrap 95% CI (-.110; -.011)), depression (bootstrap 95% CI (-.082; -.004)), and mindfulness (bootstrap 95% CI (-.082; -.002)), significantly mediated the intervention effect on fatigue severity, whereas sleep quality (bootstrap 95% CI (-.081; .009)), sleep disturbance (bootstrap 95% CI (-.038; .029)), and physical activity (bootstrap 95% CI (-.068; .000)) did not. Similar associations were found for fatigue interference.

CONCLUSIONS: Untire app access reduces fatigue severity and interference mainly by decreasing fatigue catastrophizing, depression, and by increasing mindfulness. Supporting these psychological mechanisms is crucial for reducing fatigue among cancer patients and survivors. This article is protected by copyright. All rights reserved.

PMID:35060222 | DOI:10.1002/pon.5886

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