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Single-staged in vivo co-transplantation of autologous muscular and urothelial micrografts as a composite tissue tube for urogenital reconstruction
No full textPurposeTissue-engineered grafts conventionally rely on resource-intensive ex vivo cellularization. Perioperative autologous micrografting allows for direct single-staged graft cellularization omitting laboratory-based in vitro propagation. For urogenital reconstruction, where a muscular layer may be desirable, co-transplanting muscular and urothelial micrografts has previously shown to inhibit urothelial micrograft expansion. This study aimed to assess the effects of adding muscular micrografts in a separate compartment in a tubular collagen-based urinary graft.MethodsAutologous tissue from twelve minipig bladders was used for implanting tubular grafts that were constructed and implanted subcutaneously as a single-staged in vivo procedure. Each animal received four grafts: two containing urothelial micrografts only (urothelial group) and two containing both urothelial and detrusor muscle micrografts (co-transplanted group).ResultsSix weeks post-implantation, 74% of the urothelial group and 64% of the co-transplanted tubular grafts demonstrated luminal pancytokeratin-positive epithelium (p = 0.524). Grafts were analyzed histologically and by immunoassays for identification of epithelium (pancytokeratin), differentiated urothelium (uroplakin II), smooth muscle (α-SMA & desmin), inflammation (CD68 & apoptosis assay), and vascularization (CD31+ vessels). No significant differences in cellular markers or epithelization were observed between groups.ConclusionOur findings indicate that muscular micrografts can be co-transplanted in a separate compartment in a collagen-based tubular graft without inhibiting co-transplanted urothelial micrograft expansion.PURPOSE: Tissue-engineered grafts conventionally rely on resource-intensive ex vivo cellularization. Perioperative autologous micrografting allows for direct single-staged graft cellularization omitting laboratory-based in vitro propagation. For urogenital reconstruction, where a muscular layer may be desirable, co-transplanting muscular and urothelial micrografts has previously shown to inhibit urothelial micrograft expansion. This study aimed to assess the effects of adding muscular micrografts in a separate compartment in a tubular collagen-based urinary graft.METHODS: Autologous tissue from twelve minipig bladders was used for implanting tubular grafts that were constructed and implanted subcutaneously as a single-staged in vivo procedure. Each animal received four grafts: two containing urothelial micrografts only (urothelial group) and two containing both urothelial and detrusor muscle micrografts (co-transplanted group).RESULTS: Six weeks post-implantation, 74% of the urothelial group and 64% of the co-transplanted tubular grafts demonstrated luminal pancytokeratin-positive epithelium (p = 0.524). Grafts were analyzed histologically and by immunoassays for identification of epithelium (pancytokeratin), differentiated urothelium (uroplakin II), smooth muscle (α-SMA & desmin), inflammation (CD68 & apoptosis assay), and vascularization (CD31+ vessels). No significant differences in cellular markers or epithelization were observed between groups.CONCLUSION: Our findings indicate that muscular micrografts can be co-transplanted in a separate compartment in a collagen-based tubular graft without inhibiting co-transplanted urothelial micrograft expansion.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00383-025-06259-5.</p
Relapse-related outcomes in the Danish population-based AQP4- antibody seropositive neuromyelitis optica spectrum disorder cohort
No full textBackgroundThe disease course of AQP4-antibody seropositive neuromyelitis optica spectrum disorder (AQP4-Ab + NMOSD) is unpredictable and variable. We aimed to examine relapse-related outcomes.MethodsIn a nationwide historically prospective AQP4-Ab + NMOSD cohort, relapse outcomes, relapse and maintenance treatments were analyzed by mixed-effects linear and logistic regression models.ResultsAmong sixty-six patients (median follow-up: 99.5 months) there were 350 relapses and 272 relapse treatments. Delayed immunosuppression after the first relapse and brainstem (BS) relapses were associated with higher Expanded Disability Status Scale (EDSS) scores at final follow-up. Optic neuritis (ON) was associated with higher relapse frequency. Higher age and male sex were associated with more severe transverse myelitis (TM) (p < 0.032), and male sex was also associated with worse ON recovery (p = 0.036). ON was more likely after TM (OR: 3.2, 95% CI: 1.7-6.0; p < 0.001) and vice versa (OR: 2.9, 95% CI: 1.6–5.2; p < 0.001). BS relapse was also more likely after TM (OR: 2.8, 95% CI: 1.2–6.4; p = 0.016) and vice versa (OR: 2.4; 95% CI: 1.1–5.3; p = 0.031). Rituximab treatment correlated with lower EDSS score at final follow-up (p = 0.044).ConclusionEarlier initiation of immunosuppressive maintenance treatment limited the accumulation of disability in NMOSD. Recognizing relapse patterns could aid in tailoring monitoring and treatment choices.BACKGROUND: The disease course of AQP4-antibody seropositive neuromyelitis optica spectrum disorder (AQP4-Ab + NMOSD) is unpredictable and variable. We aimed to examine relapse-related outcomes.METHODS: In a nationwide historically prospective AQP4-Ab + NMOSD cohort, relapse outcomes, relapse and maintenance treatments were analyzed by mixed-effects linear and logistic regression models.RESULTS: Among sixty-six patients (median follow-up: 99.5 months) there were 350 relapses and 272 relapse treatments. Delayed immunosuppression after the first relapse and brainstem (BS) relapses were associated with higher Expanded Disability Status Scale (EDSS) scores at final follow-up. Optic neuritis (ON) was associated with higher relapse frequency. Higher age and male sex were associated with more severe transverse myelitis (TM) (p < 0.032), and male sex was also associated with worse ON recovery (p = 0.036). ON was more likely after TM (OR: 3.2, 95% CI: 1.7-6.0; p < 0.001) and vice versa (OR: 2.9, 95% CI: 1.6-5.2; p < 0.001). BS relapse was also more likely after TM (OR: 2.8, 95% CI: 1.2-6.4; p = 0.016) and vice versa (OR: 2.4; 95% CI: 1.1-5.3; p = 0.031). Rituximab treatment correlated with lower EDSS score at final follow-up (p = 0.044).CONCLUSION: Earlier initiation of immunosuppressive maintenance treatment limited the accumulation of disability in NMOSD. Recognizing relapse patterns could aid in tailoring monitoring and treatment choices.</p
Early Detection of Pulmonary Congestion Using Quantitative CT and Lung US in a Porcine Model
No full textPurpose To assess the value of quantitative CT and lung US in detecting pulmonary congestion across successive stages in a porcine model. Materials and Methods Eleven pigs (female, 5 months old) were examined (February 2016-September 2016) every 15 minutes during the induction (steps 2-5) and treatment (steps 6-8) of pulmonary congestion. All animals were assessed with quantitative CT, lung US, an arterial pulse contour cardiac output catheter, and right heart catheterization to measure lung water content, lung attenuation and B-lines, central venous pressure, pulmonary capillary wedge pressure (PCWP), cardiac output, and global end-diastolic volume. Correlation analyses were performed, and diagnostic performance of quantitative CT and lung US for detecting pulmonary congestion was assessed using the area under the receiver operating characteristic curve (AUC). Results Nine of eleven pigs (82%) completed the full protocol. The median quantitative CT attenuation showed high correlation with PCWP, especially during the intervention stage (r = 0.99; P < .05). Compared with no congestion (step 1), milder stages (step 2) of congestion were better identified using quantitative CT (AUC, 0.92) versus US B-lines (AUC, 0.50; P < .001). However, the two modalities did not differ in ability to detect more-severe stages of congestion (Pstep3 = .14; Pstep4 = .44; Pstep5 = .75). During recovery, quantitative CT attenuation remained different from baseline levels (P = .01), whereas lung US B-lines reverted to baseline levels more rapidly (P = .63). Conclusion Quantitative CT showed high performance for assessing pulmonary congestion in its earliest subclinical stages. US B-lines were less sensitive, first appearing in the later stages of pulmonary congestion, but were more effective for monitoring regression of pulmonary congestion. </p
Revealing nested archetypes of cropland abandonment based on social-ecological system theory
No full textCropland abandonment is a key land-use change process within the human-environment system, shaped by diverse environmental and socio-economic determinants. However, many studies overlook the complex interrelationships among these determinants, which may result in the reconfiguration of agricultural landscapes. Here, we developed an analytic framework based on social-ecological system theory to map cropland abandonment archetypes in Sichuan Province, Southwest China, using a combination of biophysical conditions, proximity characteristics, socio-economic determinants, and the extent, cumulative proportion, and spatial configuration of abandoned croplands. We implemented self-organizing feature maps using a nested clustering approach, which resulted in 25 sub-archetypes and 6 meta-archetypes. We used random forest regressions to quantify the relative importance of explanatory determinants influencing archetype geographies. Our results revealed diverse cropland abandonment archetypes, with meta-archetype area shares ranging from 4.4 % to 48.4 %. The most widespread archetype was characterized by favorable terrain, low cropland per capita, and low cumulative proportions of abandonment. Determinants of meta-archetypes varied in their importance but consistently highlighted the role of environmental determinants (i.e., topography, temperature), as well as productivity-related and socio-economic determinants (i.e., employee wages, pension insurance, high-value crops) as the most important determinants. Our findings argue against one-size-fits-all solutions and are highly relevant to nuance existing regional land-use policies addressing cropland abandonment. They further allow targeting key determinants of cropland abandonment and considering regional and local socio-ecological contexts in decision-making processes.</p
Not Just Neurons:Pain Is Orchestrated in Partnership with Many Non-neuronal Cells
No full textPain is a symptom common to a wide variety of conditions and one that severely impacts an individual's everyday life, as well as having broader socioeconomic repercussions. In recent years, there has been spectacularly rapid progress in the understanding of the molecular basis of sensory neuron function and pain in preclinical models. However, the number of analgesics interacting with novel targets that have received regulatory approval in recent years has been limited. Examples include monoclonal antibody and small molecule therapies disrupting calcitonin gene-related peptide signaling for treating migraine and, most recently, suzetrigine, a small molecular inhibitor of the voltage-gated sodium channel NaV1.8 subunit. In this review, we step away from focusing on the sensory neuron as the transmitter of nociceptive information and examine the role of non-neuronal cells in modulating sensory neuron activity. One potential appeal of disrupting the activity of peripherally located non-neuronal cells is the likely bypassing of side effects associated with modulating a target receptor that is expressed by neurons within both the peripheral and central nervous systems, although targeting of peripheral, non-neuronal cells will not of course necessarily be side effect-free. Here, we examine the key roles of non-neuronal cells in orchestrating pain across a diverse set of conditions, from joint pain to bone pain, chemotherapy-induced neuropathic pain, Fabry disease, and chronic pain in general.</p
Postoperative Pain Treatment After Pancreatic Surgery. A Protocol for Systematic Review With Meta-Analysis and Trial Sequential Analysis
No full textBACKGROUND: Pancreatic surgical procedures are technically challenging and associated with a high level of surgical stress and postoperative pain. The most common surgical intervention in the pancreas is a pancreatoduodenectomy seconded by a distal pancreas resection and total pancreatectomy. Optimal pain management is crucial for ensuring early mobilization and has been shown to reduce the length of hospital stay and the incidence of postoperative complications. The optimal strategy, however, remains a matter of controversy, and the advantages and harms related to the use of different analgesic interventions remain unclear.OBJECTIVES: This systematic review aims to investigate the benefits and harms of analgesic interventions in adult patients undergoing total pancreatectomy, pancreatoduodenectomy and distal pancreatectomy.METHODS: The protocol adheres to The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. A search will be conducted in Medline, EMBASE, and The Cochrane Library's CENTRAL for published and ongoing trials. We will include randomized clinical trials that assess the postoperative effect of an intervention compared to a control. A risk of bias assessment will be performed according to risk of bias volume 2 (ROB2), and trial sequential analysis will be conducted. Furthermore, a meta-analysis will be conducted in accordance with the recommendations outlined in the Cochrane Handbook for Systematic Reviews and Interventions. The Review Manager Software version 5.4 will be used to handle the analyses. The overall quality of evidence for outcomes derived from the meta-analysis, risk of bias, and trial sequential analysis will be evaluated using the GRADE approach.</p
Clinical Criteria to Guide Antineuronal Antibody Testing for People With Early and Persistent Psychosis Attending Mental Health Services
No full textBackground Early detection of autoimmune psychosis (AP) mediated by antineuronal antibodies (Abs) is critical for achieving optimal clinical outcomes. However, evidence remains limited regarding who should be tested and how Ab-positive cases should be managed. In this large-scale study, we evaluated proposed clinical criteria for targeted Ab testing in psychiatric services and described the clinical course of seropositive patients. Methods Individuals with early psychosis (EP) or persistent psychosis (PP) were prospectively assessed with clinical criteria to determine high- or low-risk status for AP. Blood samples were collected for Ab testing using a fixed cell-based assay. Seropositive individuals were invited for detailed review, including clinical, functional, and cognitive assessments at baseline and a 12-month follow-up. Blood samples were collected from 754 individuals (EP: n = 352, PP: n = 402). Results Abs were present in 2.3% (17/754), including 3.4% (12/352) of patients with EP and 1.2% (5/402) of patients with PP. AP was confirmed in 2 cerebrospinal fluid (CSF)–positive high-risk individuals (total: 2/754, 0.3%; EP: 1/352, 0.3%; PP: 1/402, 0.2%). Both improved with immunotherapy. Although some low-risk patients were seropositive, none were diagnosed clinically with AP. Conclusions AP prevalence was low in this cohort. Targeted testing informed by clinical high-risk criteria successfully identified 2 immunotherapy-responsive AP cases. This approach appears feasible but requires further validation. People with psychosis and high-risk AP features should be considered for Ab testing in sera and CSF where indicated. Further research is required to embed targeted Ab testing into mental health services.</p
Remnant cholesterol and particle number of VLDL subfractions in coronary artery disease:Pros and cons
No full textEmerging evidence from large observational studies and causal genetic studies suggest that elevated very-low-density lipoproteins (VLDL) are important and independent risk factors for atherosclerosis, myocardial infarction, and coronary artery disease. The cholesterol content of VLDL particles is often combined as overall remnant cholesterol; however, VLDL particles encompasses a heterogeneous group of lipoproteins that vary significantly in size, density, and structural composition, contributing to metabolic heterogeneity of VLDL particles. This heterogeneity has been suggested important for understanding the atherogenicity of VLDL particles. Nevertheless, remnant cholesterol lack precision to capture metabolic heterogeneity of VLDL subfractions; in contrast, advanced techniques such as nuclear magnetic resonance (NMR) spectroscopy provide more accurate estimates of VLDL particle number and cholesterol content across subfractions. This review aims at summarizing current evidence of the association between remnant cholesterol and particle number of VLDL subfractions as risk factors for myocardial infarction and coronary artery disease including pros and cons for using easily accessible remnant cholesterol versus using more advanced measurement methods for estimation of particle number of VLDL subfractions.</p