Interleukin-3 coordinates glial-peripheral immune crosstalk to incite multiple sclerosis.

Glial cells and central nervous system (CNS)-infiltrating leukocytes contribute to multiple sclerosis (MS). However, the networks that govern crosstalk among these ontologically distinct populations remain unclear. Here, we show that, in mice and humans, CNS-resident astrocytes and infiltrating CD44hiCD4+ T cells generated interleukin-3 (IL-3), while microglia and recruited myeloid cells expressed interleukin-3 receptor-ɑ (IL-3Rɑ). Astrocytic and T cell IL-3 elicited an immune migratory and chemotactic program by IL-3Rɑ+ myeloid cells that enhanced CNS immune cell infiltration, exacerbating MS and its preclinical model. Multiregional snRNA-seq of human CNS tissue revealed the appearance of IL3RA-expressing myeloid cells with chemotactic programming in MS plaques. IL3RA expression by plaque myeloid cells and IL-3 amount in the cerebrospinal fluid predicted myeloid and T cell abundance in the CNS and correlated with MS severity. Our findings establish IL-3:IL-3RA as a glial-peripheral immune network that prompts immune cell recruitment to the CNS and worsens MS.

Observed poleward freshwater transport since 1970.

Warming-induced global water cycle changes pose a significant challenge to global ecosystems and human society. However, quantifying historical water cycle change is difficult owing to a dearth of direct observations, particularly over the ocean, where 77% and 85% of global precipitation and evaporation occur, respectively1-3. Air-sea fluxes of freshwater imprint on ocean salinity such that mean salinity is lowest in the warmest and coldest parts of the ocean, and is highest at intermediate temperatures4. Here we track salinity trends in the warm, salty fraction of the ocean, and quantify the observed net poleward transport of freshwater in the Earth system from 1970 to 2014. Over this period, poleward freshwater transport from warm to cold ocean regions has occurred at a rate of 34-62 milli-sverdrups (mSv = 103 m3 s-1), a rate that is not replicated in the current generation of climate models (the Climate Model Intercomparison Project Phase 6 (CMIP6)). In CMIP6 models, surface freshwater flux intensification in warm ocean regions leads to an approximately equivalent change in ocean freshwater content, with little impact from ocean mixing and circulation. Should this partition of processes hold for the real world, the implication is that the historical surface flux amplification is weaker (0.3-4.6%) in CMIP6 compared with observations (3.0-7.4%). These results establish a historical constraint on poleward freshwater transport that will assist in addressing biases in climate models.

Dissection of complement and Fc-receptor-mediated pathomechanisms of autoantibodies to myelin oligodendrocyte glycoprotein.

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) have recently been established to define a new disease entity, MOG-antibody-associated disease (MOGAD), which is clinically overlapping with multiple sclerosis. MOG-specific antibodies (Abs) from patients are pathogenic, but the precise effector mechanisms are currently still unknown and no therapy is approved for MOGAD. Here, we determined the contributions of complement and Fc-receptor (FcR)-mediated effects in the pathogenicity of MOG-Abs. Starting from a recombinant anti-MOG (mAb) with human IgG1 Fc, we established MOG-specific mutant mAbs with differential FcR and C1q binding. We then applied selected mutants of this MOG-mAb in two animal models of experimental autoimmune encephalomyelitis. First, we found MOG-mAb-induced demyelination was mediated by both complement and FcRs about equally. Second, we found that MOG-Abs enhanced activation of cognate MOG-specific T cells in the central nervous system (CNS), which was dependent on FcR-, but not C1q-binding. The identification of complement-dependent and -independent pathomechanisms of MOG-Abs has implications for therapeutic strategies in MOGAD.

Fully magnetically centrifugal left ventricular assist device and long-term outcomes: the ELEVATE registry.

BACKGROUND AND AIMS: HeartMate 3 (HM3) is a fully magnetically levitated continuous flow left ventricular assist device, which received CE marking in 2015. The ELEVATE Registry was initiated to collect real-world outcomes in patients treated with HM3 post-CE Mark approval. METHODS: A total of 540 subjects implanted at 26 centres between March 2015 and February 2017 were included in this registry. Of these, 463 received the device as a primary implant (primary implant cohort, PIC), 19 as a pump exchange (pump exchange cohort), and in 58 patients, only anonymized survival data were collected (anonymized cohort, AC). Patients in the PIC contributed to the baseline demographics, survival, adverse events, quality of life (QoL) (EuroQoL-5 Dimensions-5 Levels visual analogue scale), and functional capacity (6 min walk distance) assessments, while patients in the AC contributed only to survival. RESULTS: Primary implant cohort patients had a mean age of 56 years and were predominantly male (89%) with 48% ischaemic aetiology. The majority of subjects was designated bridge to transplant (66%) and had INTERMACS Profiles 1-3 (70%). At baseline, the subjects had poor functional capacity (104 ± 140 m) and impaired QoL (35 ± 19 points). The overall survival rate of the PIC was 63.3% and survival free of stroke was 58.1% at 5 years. Significant improvements in functional capacity and QoL were observed and maintained for 5 years (301 ± 131 m and 64 ± 20 points, respectively). CONCLUSIONS: Real-world data from the ELEVATE registry demonstrate an overall survival rate for primary implants of 63.3%. In the PIC, reductions in adverse events for patients in the extended follow-up and improved QoL and functional capacity were observed at 5 years in this patient population with advanced heart failure.

Ingesting yeast extract causes excitation of neurogenic and myogenic colonic motor patterns in the rat.

Fermented foods play a significant role in the human diet for their natural, highly nutritious and healthy attributes. Our aim was to study the effect of yeast extract, a fermented substance extracted from natural yeast, on colonic motility to better understand its potential therapeutic role. A yeast extract was given to rats by gavage for 3 days, and myogenic and neurogenic components of colonic motility were studied using spatiotemporal maps made from video recordings of the whole colon ex vivo. A control group received saline gavages. The yeast extract caused excitation of the musculature by increasing the propagation length and duration of long-distance contractions, the major propulsive activity of the rat colon. The yeast extract also evoked rhythmic propulsive motor complexes (RPMCs) which were antegrade in the proximal and mid-colon and retrograde in the distal colon. RPMC activity was evoked by distention-induced neural activity, but it was myogenic in nature since we showed it to be generated by bethanechol in the presence of tetrodotoxin. In conclusion, ingestion of yeast extract stimulates rat colon motility by exciting neurogenic and myogenic control mechanisms.

Single-cell transcriptomics reveal distinctive patterns of fibroblast activation in heart failure with preserved ejection fraction.

Inflammation, fibrosis and metabolic stress critically promote heart failure with preserved ejection fraction (HFpEF). Exposure to high-fat diet and nitric oxide synthase inhibitor N[w]-nitro-l-arginine methyl ester (L-NAME) recapitulate features of HFpEF in mice. To identify disease-specific traits during adverse remodeling, we profiled interstitial cells in early murine HFpEF using single-cell RNAseq (scRNAseq). Diastolic dysfunction and perivascular fibrosis were accompanied by an activation of cardiac fibroblast and macrophage subsets. Integration of fibroblasts from HFpEF with two murine models for heart failure with reduced ejection fraction (HFrEF) identified a catalog of conserved fibroblast phenotypes across mouse models. Moreover, HFpEF-specific characteristics included induced metabolic, hypoxic and inflammatory transcription factors and pathways, including enhanced expression of Angiopoietin-like 4 (Angptl4) next to basement membrane compounds, such as collagen IV (Col4a1). Fibroblast activation was further dissected into transcriptional and compositional shifts and thereby highly responsive cell states for each HF model were identified. In contrast to HFrEF, where myofibroblast and matrifibrocyte activation were crucial features, we found that these cell states played a subsidiary role in early HFpEF. These disease-specific fibroblast signatures were corroborated in human myocardial bulk transcriptomes. Furthermore, we identified a potential cross-talk between macrophages and fibroblasts via SPP1 and TNFɑ with estimated fibroblast target genes including Col4a1 and Angptl4. Treatment with recombinant ANGPTL4 ameliorated the murine HFpEF phenotype and diastolic dysfunction by reducing collagen IV deposition from fibroblasts in vivo and in vitro. In line, ANGPTL4, was elevated in plasma samples of HFpEF patients and particularly high levels associated with a preserved global-longitudinal strain. Taken together, our study provides a comprehensive characterization of molecular fibroblast activation patterns in murine HFpEF, as well as the identification of Angiopoietin-like 4 as central mechanistic regulator with protective effects.

Prevalence of type II endoleak after elective endovascular aneurysm repair with polytetrafluoroethylene- or polyester-based endografts.

OBJECTIVE: Type II endoleak is the most frequent complication after endovascular abdominal aneurysm repair. Polytetrafluoroethylene and polyester (PE) are the two most commonly used graft materials in endovascular aneurysm repair (EVAR) devices. Biological properties of the material might influence the appearance and persistence of type II endoleak (T2EL). Therefore, the aim of this study was to evaluate potential differences in the prevalence of T2EL after EVAR between polytetrafluoroethylene (PTFE) and PE endografts in patients electively treated for an infrarenal abdominal aortic aneurysm. METHODS: A single-center, retrospective, observational study was conducted between January 2011 and January 2022. Preoperative, procedural, and follow-up data were derived from electronic health records. Imaging included computed tomography scans, and/or duplex ultrasound examination. The primary end point was the prevalence of T2EL diagnosed within 1 year after EVAR. Secondary end points included the prevalence of T2EL throughout follow-up, early (≤30 days) and late (>30 days) T2EL, the rate of T2EL disappearance during the follow-up period, the prevalence of type I and III endoleak, and T2EL-related reinterventions. RESULTS: Follow-up was available for 394 patients, 245 in the PE and 149 in the PTFE group. The prevalence of T2EL diagnosed within 1 year after endovascular repair was 11.8% in the PE group and 21.5% in the PTFE group (P = .010). There was no significant difference in early (≤30 days) and late (>30 days) T2EL between groups (P = .270 and P = .311). There was no difference in the freedom from endoleak type II reinterventions between groups (P = .877). CONCLUSIONS: The prevalence of T2EL after elective EVAR is significantly higher with the use of PTFE-based endografts compared with PE-based endografts. This difference is mostly based on T2EL diagnosed after 30 days of follow-up.

An international, expert-based, Delphi consensus document on controversial issues in the management of abdominal aortic aneurysms.

OBJECTIVE: As a result of conflicting, inadequate or controversial data in the literature, several issues concerning the management of patients with abdominal aortic aneurysms (AAAs) remain unanswered. The aim of this international, expert-based Delphi consensus document was to provide some guidance for clinicians on these controversial topics. METHODS: A three-round Delphi consensus document was produced with 44 experts on 6 prespecified topics regarding the management of AAAs. All answers were provided anonymously. The response rate for each round was 100%. RESULTS: Most participants (42 of 44 [95.4%]) agreed that a minimum case volume per year is essential (or probably essential) for a center to offer open or endovascular AAA repair (EVAR). Furthermore, 33 of 44 (75.0%) believed that AAA screening programs are (probably) still clinically effective and cost effective. Additionally, most panelists (36 of 44 [81.9%]) voted that surveillance after EVAR should be (or should probably be) lifelong. Finally, 35 of 44 participants (79.7%) thought that women smokers should (or should probably/possibly) be considered for screening at 65 years of age, similar to men. No consensus was achieved regarding lowering the threshold for AAA repair and the need for deep venous thrombosis prophylaxis in patients undergoing EVAR. CONCLUSIONS: This expert-based Delphi consensus document provides guidance for clinicians regarding specific unresolved issues. Consensus could not be achieved on some topics, highlighting the need for further research in those areas.

Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis.

BACKGROUND: We aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS). METHODS: A total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman's r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods. RESULTS: Median (IQR) age of patients was 52.9 (46.4-58.5) years, and 58 (41.1%) were men. Median follow-up time was 9.1 (7.0-12.6) years. Only 8 (5.7%) patients received treatment during follow-up. sNfL and sGFAP levels were moderately correlated (r=0.43) and both weakly correlated with sCHI3L1 levels (r=0.19 and r=0.17, respectively). In multivariable analyses, levels of the three biomarkers were associated with EDSS changes across all time periods. However, when analysis was restricted to non-inflammatory patients according to clinical and radiological parameters (n=64), only sCHI3L1 levels remained associated with future EDSS change. CONCLUSIONS: Levels of sNfL, sGFAP and sCHI3L1 are prognostic biomarkers associated with disability progression in patients with PPMS, being CHI3L1 findings less dependent on the inflammatory component associated with disease progression.

Cytomegalovirus immune responses are associated with lower serum NfL and disability accumulation risk at multiple sclerosis onset.

BACKGROUND: Infection by cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) play a prognostic role in multiple sclerosis (MS). OBJECTIVES: To explore whether humoral immune responses to HCMV and EBV at disease onset were associated with changes in serum and cerebrospinal fluid (CSF) levels of inflammatory and neurodegeneration biomarkers. METHODS: Ninety-eight MS patients with a median follow-up of 20 years were included in the study. The levels of a panel of nine biomarkers were measured in serum (N = 60) and CSF (N = 61) samples of patients at the time of the first demyelinating event. RESULTS: Immune responses to HCMV inversely correlated with serum neurofilament light chain (sNfL) levels (rho = -0.367; p = 0.039). sNfL levels were reduced in patients with high immune responses to HCMV (p = 0.006). Elevated sNfL levels were associated with higher risk of Expanded Disability Status Scale (EDSS) 3.0 (p = 0.016), 4.0 (p = 0.009) and 6.0 (p = 0.003), and with higher risk of developing secondary progressive MS (p = 0.003) and to receive treatment (p = 0.032). Serum soluble CD21 levels were increased in patients with high immune responses to EBV nuclear antigen 1 (p = 0.020). CONCLUSIONS: High immune responses to HCMV are associated with limited disease progression and central nervous system (CNS) injury in MS patients. These findings reinforce the protective role of HCMV infection in MS.

High-sensitive troponin T, suPAR and Beta-2-microglobulin changes in concentration during hemodialysis.

Hemodialysis (HD) patients are at high risk of cardiovascular disease and death. Reliable biomarkers for risk stratification and detection of acute myocardial infarction (AMI) are therefore pivotal. Cardiac troponins (cTn) are the preferred biomarkers for AMI. It remains unclear, if cTn concentrations changes as a consequence of HD treatment itself during dialysis. In this study, cTn was compared with soluble urokinase plasminogen activator receptor (suPAR) and Beta-2-microglobulin (B2M). We performed a prospective study including 17 HD patients measuring high-sensitive cardiac troponin t (hs-cTnT), suPAR and B2M before and after a dialysis session and verified the results in a random subgroup of eight patients from the group by repeating their measurements before and after a dialysis session 15 weeks later. Biomarker concentrations after dialysis were adjusted according to hemodilution or concentration according to the hemoglobin concentration. The average hs-cTnT concentration decreased significantly by -9.9% after dialysis (95% CI: -13.6% to -6.2%). The average (paired) difference were - 6.7 ng/L (p = 0.0104) after dialysis comparing 25 HD treatment occasions. SuPAR was not significantly influenced by dialysis. B2M decreased by -58% after HD as an expected result from the molecular size of the biomarker. The hs-cTnT in average decreased by -9.9% after dialysis. This is a diagnostic challenge since the current guidelines suggest a 20% change in hs-cTnT in patients with acute myocardial infarction. Larger prospective studies investigating the different factors influencing hs-cTnT after HD are warranted. Adjusting biomarker concentrations according to hemodilution or concentration using the hemoglobin concentration, should be considered in future studies to determine more exact changes in concentrations of cTnT and other relevant biomarkers.

A scoping review of post-earthquake healthcare for vulnerable groups of the 2023 Turkey-Syria earthquakes.

BACKGROUND: Identifying healthcare services and also strengthening the healthcare systems to effectively deliver them in the aftermath of large-scale disasters like the 2023 Turkey-Syria earthquakes, especially for vulnerable groups cannot be emphasized enough. This study aimed at identifying the interventions undertaken or proposed for addressing the health needs or challenges of vulnerable groups immediately after the occurrence of the 2023 Turkey-Syria earthquakes, as well as for prioritizing their healthcare service delivery in the post-Turkey-Syria earthquake. METHODS: In this scoping review compiled with the five steps of the Arksey and O'Malley framework, five databases, including PubMed, Science Direct, Web of Science, OVID, and Google Scholar, were searched for studies published between March and April 2023 in line with the eligibility criteria. Interventions for enhancing post-earthquake healthcare services (PEHS) were grouped into seven (7) categories, adopted from previous guidelines and studies. Each one was assigned a default score of a value equal to one (1), which, in the end, was summed up. RESULTS: Of the 115 total records initially screened, 29 articles were eligible for review. Different interventions they reported either undertaken or proposed to address the healthcare needs and challenges, especially faced by the most vulnerable groups in the aftermath of the Turkey-Syria earthquakes, were categorized into 7 PEHS. They were ranked with their scores as follows: humanitarian health relief (25); medical care (17); mental health and psychosocial support (10); health promotion, education, and awareness (9); disease surveillance and prevention (7); disability rehabilitation (7); and sexual and reproductive health (5). CONCLUSION: Since there are no proper guidelines or recommendations about the specific or most significant PEHS to prioritize for vulnerable groups after the occurrence of large-scale earthquakes, this scoping review provides some insights that can help inform healthcare service delivery and prioritization for vulnerable groups in the post-2023 Turkey-Syria earthquakes and other similar disasters.

Impact of an enhanced recovery after surgery program integrating cardiopulmonary rehabilitation on post-operative prognosis of patients treated with CABG: protocol of the ERAS-CaRe randomized controlled trial.

BACKGROUND: Coronary artery bypass grafting is associated with a high occurrence of postoperative cardiopulmonary complications. Preliminary evidence suggested that enhanced recovery after surgery can effectively reduce the occurrence of postoperative cardiopulmonary complications. However, enhanced recovery after surgery with systematic integration of cardiopulmonary rehabilitation (ERAS-CaRe) into for Coronary artery bypass grafting has not been evaluated so far. We thus design the ERAS-CaRe randomized-controlled trial to evaluate possible superiority of embedding cardiopulmonary rehabilitation in ERAS over ERAS alone as well as to investigate effects of differential timing of cardiopulmonary rehabilitation within enhanced recovery after surgery (pre-, post-, perio-operative) on post-operative cardiopulmonary complications following Coronary artery bypass grafting surgery. METHODS: ERAS-CaRe is a pragmatic, randomized-controlled, parallel four-arm, clinical trial. Three hundred sixty patients scheduled for Coronary artery bypass grafting in two Chinese hospitals will be grouped randomly into (i) Standard enhanced recovery after surgery or (ii) pre-operative ERAS-CaRe or (iii) post-operative ERAS-CaRe or (iv) perio-operative ERAS-CaRe. Primary outcome is the occurrence of cardiopulmonary complications at 10 days after Coronary artery bypass grafting. Secondary outcomes include the occurrence of other individual complications including cardiac, pulmonary, stroke, acute kidney injury, gastrointestinal event, ICU delirium rate, reintubation rate, early drainage tube removal rate, unplanned revascularization rate, all-cause mortality, ICU readmission rate, plasma concentration of myocardial infarction-related key biomarkers etc. DISCUSSION: The trial is designed to evaluate the hypothesis that a cardiopulmonary rehabilitation based enhanced recovery after surgery program reduces the occurrence of cardiopulmonary complications following Coronary artery bypass grafting and to determine optimal timing of cardiopulmonary rehabilitation within enhanced recovery after surgery. The project will contribute to increasing the currently limited knowledge base in the field as well as devising clinical recommendations. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trials Registry on 25 August 2023 (ChiCTR2300075125; date recorded: 25/8/2023, https://www.chictr.org.cn/ ).

Effectiveness of a socioecological model-guided, smart device-based, self-management-oriented lifestyle intervention in community residents: protocol for a cluster-randomized controlled trial.

BACKGROUND: Healthy lifestyles are crucial for preventing chronic diseases. Nonetheless, approximately 90% of Chinese community residents regularly engage in at least one unhealthy lifestyle. Mobile smart devices-based health interventions (mHealth) that incorporate theoretical frameworks regarding behavioral change in interaction with the environment may provide an appealing and cost-effective approach for promoting sustainable adaptations of healthier lifestyles. We designed a randomized controlled trial (RCT) to evaluate the effectiveness of a socioecological model-guided, smart device-based, and self-management-oriented lifestyles (3SLIFE) intervention, to promote healthy lifestyles among Chinese community residents. METHODS: This two-arm, parallel, cluster-RCT with a 6-month intervention and 6-month follow-up period foresees to randomize a total of 20 communities/villages from 4 townships in a 1:1 ratio to either intervention or control. Within these communities, a total of at least 256 community residents will be enrolled. The experimental group will receive a multi-level intervention based on the socioecological model supplemented with a multi-dimensional empowerment approach. The control group will receive information only. The primary outcome is the reduction of modifiable unhealthy lifestyles at six months, including smoking, excess alcohol consumption, physical inactivity, unbalanced diet, and overweight/obesity. A reduction by one unhealthy behavior measured with the Healthy Lifestyle Index Score (HLIS) will be considered favorable. Secondary outcomes include reduction of specific unhealthy lifestyles at 3 months, 9 months, and 12 months, and mental health outcomes such as depression measured with PHQ-9, social outcomes such as social support measured with the modified Multidimensional Scale of Perceived Social Support, clinical outcomes such as obesity, and biomedical outcomes such as the development of gut microbiota. Data will be analyzed with mixed effects generalized linear models with family and link function determined by outcome distribution and accounting for clustering of participants in communities. DISCUSSION: This study will provide evidence concerning the effect of a mHealth intervention that incorporates a behavioral change theoretical framework on cultivating and maintaining healthy lifestyles in community residents. The study will provide insights into research on and application of similar mHealth intervention strategies to promote healthy lifestyles in community populations and settings. TRIAL REGISTRATION NUMBER: ChiCTR2300070575. Date of registration: April 17, 2023. https://www.chictr.org.cn/index.aspx .

Effectiveness of Rehabilitation Interventions in Individuals With Emerging Virtual Respiratory Tract Infectious Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: Assessing rehabilitation effectiveness for persistent symptoms post-infection with emerging viral respiratory diseases. DATA SOURCES: Systematic review of seven databases (MEDLINE, EMBASE, Cochrane Library, PEDro, MedRxiv, CNKI, Wanfang) until 30 December 2023. REVIEW METHODS: Evaluated 101 studies (9593 participants) on respiratory function, exercise capacity, and quality of life. Methodological quality was assessed using the Cochrane Collaboration's Risk of Bias tool for randomized controlled trials (RCTs), the Newcastle-Ottawa Scale (NOS) for observational studies and non-RCTs, and the NIH Quality Assessment Tools for before-after studies. RESULTS: The most common rehabilitation program combined breathing exercises with aerobic exercise or strength training. Rehabilitation interventions significantly enhanced respiratory function, as evidenced by improvements on the Borg Scale (MD, -1.85; 95% CI, -3.00 to -0.70, low certainty), the mMRC Dyspnea Scale (MD, -0.45; 95% CI, -0.72 to -0.18, low certainty), and the Multidimensional Dyspnoea-12 Scale (MD, -4.64; 95% CI, -6.54 to -2.74, moderate certainty). Exercise capacity also improved, demonstrated by results from the Six-Minute Walk Test (MD, 38.18; 95% CI, 25.33-51.03, moderate certainty) and the Sit-to-Stand Test (MD, 3.04; 95% CI, 1.07-5.01, low certainty). CONCLUSION: Rehabilitation interventions are promising for survivors of viral respiratory diseases, yet gaps in research remain. Future investigations should focus on personalizing rehabilitation efforts, utilizing remote technology-assisted programs, improving research quality, and identifying specific subgroups for customized rehabilitation strategies to achieve the best outcomes for survivors.

Systematic review of clinical guidelines and consensus statements concerning heparin and protamine dosing and monitoring of anticoagulation levels for non-cardiac arterial procedures.

OBJECTIVES: This systematic review was performed to examine all published practice Guidelines and Consensus Statements (together: GCS) on heparin dosing and monitoring during non-cardiac arterial procedures (NCAP). The objective was to scrutinize the recommendations and advice outlined within these GCS documents and to evaluate the supporting evidence for these recommendations. Additionally, the use of the activated clotting time (ACT) and target ACT values were explored. METHODS: This systematic review was performed in accordance with the PRISMA Guidelines. Medline and Embase databases were searched to identify all GCSs in the English language on NCAP. The final literature search was performed in January 2023. This search was supplemented by searching websites of relevant professional vascular surgical organizations for GCSs. Titles and abstracts were assessed by two independent reviewers. RESULTS: Of 9716 titles identified, 27 GCSs met the predefined inclusion criteria: six GCSs regarding carotid intervention, seven regarding procedures for aneurysmal disease of the abdominal aorta and iliac arteries, 12 regarding interventions for acute and chronic peripheral arterial occlusive disease and two regarding open and endovascular interventions of thoraco-abdominal aortic aneurysms. Administration of heparin is advised for al NCAP. There was high variability concerning heparin dose: both standard dose as weight based dosing (30-150 IU/kg) was advised. Recommendations on repeated doses, ACT monitoring and heparin reversal using protamine also varied widely. In none of the GCSs, the type of the ACT measuring device or used cartridges were specified. CONCLUSIONS: Large variability was found between the included GCSs with regard to the recommendations on heparin dose and target ACT values during NCAP. Advice and recommendations in GCSs were based on low-quality studies or without providing any reference at all. The described variability in recommendations emphasizes the need for large prospective (randomized) studies or the incorporation of data on heparin and the use of ACT monitoring into verified vascular surgery registries, to develop evidence-based, practical and uniform applicable recommendations.

Role of metabolic risk factors in the relationship between ambient fine particulate matter and depressive symptoms: Evidence from a longitudinal population study.

BACKGROUND: There is growing evidence indicating a connection between fine particulate matter (PM2.5) and depressive symptoms. Metabolic risk factors are critical determinants of depressive symptoms. However, the mediating role of these factors on the association between PM2.5 and depressive symptoms remains elusive. We aimed to investigate whether and to what extent metabolic risk factors mediated the link between long-term PM2.5 exposure and depressive symptoms. METHODS: This study comprised 7794 individuals aged between 30 and 79 years who participated in two waves of the on-site surveys in the China Multi-Ethnic Cohort. Ambient PM2.5 concentrations were assessed utilizing a random forest method based on satellite data. We employed the Patient Health Questionnaire-9 to assess depressive symptoms at wave 2, and the overall as well as three sub-domain symptom scores (emotional, neurovegetative, and neurocognitive symptoms) were calculated. Three metabolic risk factors, including hypertension, diabetes, and dyslipidemia, were considered. Mediation analyses were conducted to assess the indirect effects of PM2.5 on depressive symptoms through metabolic risk factors. RESULTS: We found a positive association between chronic exposure to ambient PM2.5 and overall depressive symptoms as well as the three sub-domains. In mediation analyses, metabolic risk factors partially mediated the associations of PM2.5 on depressive symptoms. The natural indirect effects (RR, 95% CI) of PM2.5 on overall, emotional, neurovegetative, and neurocognitive symptoms mediated through metabolic risk factors were 1.004(1.001, 1.007), 1.004 (1.001, 1.008), 1.004 (1.001, 1.007), and 1.003(0.999, 1.007), respectively. Larger indirect effects were found in elderly participants (mediated proportion, 29.3%), females (13.3%), and people who did not consume alcohol (19.6%). CONCLUSIONS: Metabolic risk factors may act as mediators in the relationship between chronic PM2.5 exposure and depression. Treatment of metabolic risk factors may be an opportunity to reduce the burden of depression caused by long-term exposure to PM2.5.

Instability Severity Index Score predicts recurrent shoulder instability after arthroscopic Bankart repair.

PURPOSE: The Instability Severity Index (ISI) Score was developed to preoperatively assess the risk of recurrent shoulder instability after an arthroscopic Bankart repair. This study aims to validate the use of ISI Score for predicting the risk of recurrence after an arthroscopic Bankart repair in a heterogeneous population and proposes an appropriate cut-off point for treating patients with an arthroscopic Bankart repair or otherwise. METHODS: This study analysed 99 shoulders after a traumatic dislocation that underwent arthroscopic Bankart repair with at least 3 years follow-up. Patients were divided into subcategories based on their respective ISI Score. Recurrence includes either a postoperative dislocation or perceived instability. RESULTS: The overall recurrence rate was found to be 26.3%. A significant correlation was identified between ISI Score and the recurrence rate (odds ratio [OR]: 1.545, 95% confidence interval [CI]: 1.231-1.939, p < 0.001). Furthermore, ISI Score 4-6 (OR: 4.498, 95% CI: 1.866-10.842, p < 0.001) and ISI Score > 6 (OR: 7.076, 95% CI: 2.393-20.924, p < 0.001) both had a significantly higher risk of recurrence compared to ISI Score 0-3. In ISI Score subcategories 0-3, 4-6 and >6, the recurrence rate was, respectively, 15.4%, 40.7% and 71.4%. CONCLUSION: ISI Score has predictive value in determining the recurrence risk of shoulder instability following an arthroscopic Bankart repair in a heterogeneous population. Based on the findings of this study, we recommend using arthroscopic Bankart repair in patients with ISI Score 0-3. Clinical and shared decision-making are essential in the group with ISI Score 4-6, since the recurrence rate is significantly higher than in patients with ISI Score 0-3. Arthroscopic Bankart repair is not suitable for patients with ISI Score > 6. LEVEL OF EVIDENCE: Level III.

Exploring the Ocular Surface Microbiome and Tear Proteome in Glaucoma.

Although glaucoma is a leading cause of irreversible blindness worldwide, its pathogenesis is incompletely understood, and intraocular pressure (IOP) is the only modifiable risk factor to target the disease. Several associations between the gut microbiome and glaucoma, including the IOP, have been suggested. There is growing evidence that interactions between microbes on the ocular surface, termed the ocular surface microbiome (OSM), and tear proteins, collectively called the tear proteome, may also play a role in ocular diseases such as glaucoma. This study aimed to find characteristic features of the OSM and tear proteins in patients with glaucoma. The whole-metagenome shotgun sequencing of 32 conjunctival swabs identified Actinobacteria, Firmicutes, and Proteobacteria as the dominant phyla in the cohort. The species Corynebacterium mastitidis was only found in healthy controls, and their conjunctival microbiomes may be enriched in genes of the phospholipase pathway compared to glaucoma patients. Despite these minor differences in the OSM, patients showed an enrichment of many tear proteins associated with the immune system compared to controls. In contrast to the OSM, this emphasizes the role of the proteome, with a potential involvement of immunological processes in glaucoma. These findings may contribute to the design of new therapeutic approaches targeting glaucoma and other associated diseases.

Setting proficiency standards for simulation-based mastery learning of short antegrade femoral nail osteosynthesis: a multicenter study.

BACKGROUND AND PURPOSE: Orthopedic trainees frequently perform short antegrade femoral nail osteosynthesis of trochanteric fractures, but virtual reality simulation-based training (SBT) with haptic feedback has been unavailable. We explored a novel simulator, with the aim of gathering validity evidence for an embedded test and setting a credible pass/fail standard allowing trainees to practice to proficiency. PATIENTS AND METHODS: The research, conducted from May to September 2020 across 3 Danish simulation centers, utilized the Swemac TraumaVision simulator for short antegrade femoral nail osteosynthesis. The validation process adhered to Messick's framework, covering all 5 sources of validity evidence. Participants included novice groups, categorized by training to plateau (n = 14) or to mastery (n = 10), and experts (n = 9), focusing on their performance metrics and training duration. RESULTS: The novices in the plateau group and experts had hands-on training for 77 (95% confidence interval [CI] 59-95) and 52 (CI 36-69) minutes while the plateau test score, defined as the average of the last 4 scores, was 75% (CI 65-86) and 96% (CI 94-98) respectively. The pass/fail standard was established at the average expert plateau test score of 96%. All novices in the mastery group could meet this standard and interestingly without increased hands-on training time (65 [CI 46-84] minutes). CONCLUSION: Our study provides supporting validity evidence from all sources of Messick's framework for a simulation-based test in short antegrade nail osteosynthesis of intertrochanteric hip fracture and establishes a defensible pass/fail standard for mastery learning of SBT. Novices who practiced using mastery learning were able to reach the pre-defined pass/fail standard and outperformed novices without a set goal for external motivation.