RESUMO
All cells fold their genomes, including bacterial cells, where the chromosome is compacted into a domain-organized meshwork called the nucleoid. How compaction and domain organization arise is not fully understood. Here, we describe a method to estimate the average mesh size of the nucleoid in Escherichia coli. Using nucleoid mesh size and DNA concentration estimates, we find that the cytoplasm behaves as a poor solvent for the chromosome when the cell is considered as a simple semidilute polymer solution. Monte Carlo simulations suggest that a poor solvent leads to chromosome compaction and DNA density heterogeneity (i.e., domain formation) at physiological DNA concentration. Fluorescence microscopy reveals that the heterogeneous DNA density negatively correlates with ribosome density within the nucleoid, consistent with cryoelectron tomography data. Drug experiments, together with past observations, suggest the hypothesis that RNAs contribute to the poor solvent effects, connecting chromosome compaction and domain formation to transcription and intracellular organization.
Assuntos
Cromossomos Bacterianos/química , Escherichia coli/metabolismo , Conformação de Ácido Nucleico , Solventes/química , Transcrição Gênica , Aminoglicosídeos/farmacologia , Simulação por Computador , DNA Bacteriano/química , Difusão , Escherichia coli/efeitos dos fármacos , Proteínas de Fluorescência Verde/metabolismo , Tamanho da Partícula , RNA Bacteriano/metabolismo , Ribossomos/metabolismo , Ribossomos/ultraestrutura , Transcrição Gênica/efeitos dos fármacosRESUMO
Understanding the intracellular dynamics of brain cells entails performing three-dimensional molecular simulations incorporating ultrastructural models that can capture cellular membrane geometries at nanometer scales. While there is an abundance of neuronal morphologies available online, e.g. from NeuroMorpho.Org, converting those fairly abstract point-and-diameter representations into geometrically realistic and simulation-ready, i.e. watertight, manifolds is challenging. Many neuronal mesh reconstruction methods have been proposed; however, their resulting meshes are either biologically unplausible or non-watertight. We present an effective and unconditionally robust method capable of generating geometrically realistic and watertight surface manifolds of spiny cortical neurons from their morphological descriptions. The robustness of our method is assessed based on a mixed dataset of cortical neurons with a wide variety of morphological classes. The implementation is seamlessly extended and applied to synthetic astrocytic morphologies that are also plausibly biological in detail. Resulting meshes are ultimately used to create volumetric meshes with tetrahedral domains to perform scalable in silico reaction-diffusion simulations for revealing cellular structure-function relationships. Availability and implementation: Our method is implemented in NeuroMorphoVis, a neuroscience-specific open source Blender add-on, making it freely accessible for neuroscience researchers.
Assuntos
Simulação por Computador , Neurônios , Neurônios/ultraestrutura , Neurônios/citologia , Modelos Neurológicos , Humanos , Animais , Astrócitos/citologia , Astrócitos/ultraestruturaRESUMO
Ultraliser is a neuroscience-specific software framework capable of creating accurate and biologically realistic 3D models of complex neuroscientific structures at intracellular (e.g. mitochondria and endoplasmic reticula), cellular (e.g. neurons and glia) and even multicellular scales of resolution (e.g. cerebral vasculature and minicolumns). Resulting models are exported as triangulated surface meshes and annotated volumes for multiple applications in in silico neuroscience, allowing scalable supercomputer simulations that can unravel intricate cellular structure-function relationships. Ultraliser implements a high-performance and unconditionally robust voxelization engine adapted to create optimized watertight surface meshes and annotated voxel grids from arbitrary non-watertight triangular soups, digitized morphological skeletons or binary volumetric masks. The framework represents a major leap forward in simulation-based neuroscience, making it possible to employ high-resolution 3D structural models for quantification of surface areas and volumes, which are of the utmost importance for cellular and system simulations. The power of Ultraliser is demonstrated with several use cases in which hundreds of models are created for potential application in diverse types of simulations. Ultraliser is publicly released under the GNU GPL3 license on GitHub (BlueBrain/Ultraliser). SIGNIFICANCE: There is crystal clear evidence on the impact of cell shape on its signaling mechanisms. Structural models can therefore be insightful to realize the function; the more realistic the structure can be, the further we get insights into the function. Creating realistic structural models from existing ones is challenging, particularly when needed for detailed subcellular simulations. We present Ultraliser, a neuroscience-dedicated framework capable of building these structural models with realistic and detailed cellular geometries that can be used for simulations.
Assuntos
Neurônios , Software , Simulação por ComputadorRESUMO
The functional support and advancement of our body while preserving inherent naturalness is one of the ultimate goals of bioengineering. Skin protection against infectious pathogens is an application that requires common and long-term wear without discomfort or distortion of the skin functions. However, no antimicrobial method has been introduced to prevent cross-infection while preserving intrinsic skin conditions. Here, we propose an antimicrobial skin protection platform copper nanomesh, which prevents cross-infectionmorphology, temperature change rate, and skin humidity. Copper nanomesh exhibited an inactivation rate of 99.99% for Escherichia coli bacteria and influenza virus A within 1 and 10 min, respectively. The thin and porous nanomesh allows for conformal coating on the fingertips, without significant interference with the rate of skin temperature change and humidity. Efficient cross-infection prevention and thermal transfer of copper nanomesh were demonstrated using direct on-hand experiments.
Assuntos
Anti-Infecciosos , Cobre , Infecção Hospitalar , Nanopartículas Metálicas , Pele , Anti-Infecciosos/farmacologia , Cobre/farmacologia , Infecção Hospitalar/prevenção & controle , Escherichia coli/efeitos dos fármacos , Dedos , Humanos , Vírus da Influenza A/efeitos dos fármacos , Porosidade , Pele/microbiologiaRESUMO
Septate junctions (SJs) evolved as cell-cell junctions that regulate the paracellular barrier and integrity of epithelia in invertebrates. Multiple morphological variants of SJs exist specific to different epithelia and/or phyla but the biological significance of varied SJ morphology is unclear because the knowledge of the SJ associated proteins and their functions in non-insect invertebrates remains largely unknown. Here we report cell-specific expression of nine candidate SJ genes in the early life stages of the sea urchin Strongylocentrotus purpuratus. By use of in situ RNA hybridization and single cell RNA-seq we found that the expression of selected genes encoding putatively SJ associated transmembrane and cytoplasmic scaffold molecules was dynamically regulated during epithelial development in the embryos and larvae with different epithelia expressing different cohorts of SJ genes. We focused a functional analysis on SpMesh, a homolog of the Drosophila smooth SJ component Mesh, which was highly enriched in the endodermal epithelium of the mid- and hindgut. Functional perturbation of SpMesh by both CRISPR/Cas9 mutagenesis and vivo morpholino-mediated knockdown shows that loss of SpMesh does not disrupt the formation of the gut epithelium during gastrulation. However, loss of SpMesh resulted in a severely reduced gut-paracellular barrier as quantitated by increased permeability to 3-5 âkDa FITC-dextran. Together, these studies provide a first look at the molecular SJ physiology during the development of a marine organism and suggest a shared role for Mesh-homologous proteins in forming an intestinal barrier in invertebrates. Results have implications for consideration of the traits underlying species-specific sensitivity of marine larvae to climate driven ocean change.
Assuntos
Proteínas de Drosophila , Strongylocentrotus purpuratus , Animais , Strongylocentrotus purpuratus/genética , Strongylocentrotus purpuratus/metabolismo , Junções Íntimas/genética , Junções Íntimas/metabolismo , Epitélio/metabolismo , Junções Intercelulares/metabolismo , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Ouriços-do-Mar/genética , Ouriços-do-Mar/metabolismo , Larva/genética , Larva/metabolismoRESUMO
Hosts hold great prospects for addressing the dendrite growth and volume expansion of the Li metal anode, but Li dendrites are still observable under the conditions of high deposition capacity and/or high current density. Herein, a nitrogen-doped graphene mesh (NGM) is developed, which possesses a conductive and lithiophilic scaffold for efficient Li deposition. The abundant nanopores in NGM can not only provide sufficient room for Li deposition, but also speed up Li ion transport to achieve a high-rate capability. Moreover, the evenly distributed N dopants on the NGM can guide the uniform nucleation of Li so that to inhibit dendrite growth. As a result, the composite NGM@Li anode shows satisfactory electrochemical performances for Li-S batteries, including a high capacity of 600 mAh g-1 after 300 cycles at 1 C and a rate capacity of 438 mAh g-1 at 3 C. This work provides a new avenue for the fabrication of graphene-based hosts with large areal capacity and high-rate capability for Li metal batteries.
RESUMO
Disease pathogenesis is always a major topic in biomedical research. With the exponential growth of biomedical information, drug effect analysis for specific phenotypes has shown great promise in uncovering disease-associated pathways. However, this method has only been applied to a limited number of drugs. Here, we extracted the data of 4634 diseases, 3671 drugs, 112 809 disease-drug associations and 81 527 drug-gene associations by text mining of 29 168 919 publications. On this basis, we proposed a 'Drug Set Enrichment Analysis by Text Mining (DSEATM)' pipeline and applied it to 3250 diseases, which outperformed the state-of-the-art method. Furthermore, diseases pathways enriched by DSEATM were similar to those obtained using the TCGA cancer RNA-seq differentially expressed genes. In addition, the drug number, which showed a remarkable positive correlation of 0.73 with the AUC, plays a determining role in the performance of DSEATM. Taken together, DSEATM is an auspicious and accurate disease research tool that offers fresh insights.
Assuntos
Pesquisa Biomédica , Mineração de Dados , Mineração de Dados/métodos , FenótipoRESUMO
PURPOSE: We assessed the effect of prophylactic biologic mesh on parastomal hernia (PSH) development in patients undergoing cystectomy and ileal conduit (IC). MATERIALS AND METHODS: This phase 3, randomized, controlled trial (NCT02439060) included 146 patients who underwent cystectomy and IC at the University of Southern California between 2015 and 2021. Follow-ups were physical exam and CT every 4 to 6 months up to 2 years. Patients were randomized 1:1 to receive FlexHD prophylactic biological mesh using sublay intraperitoneal technique vs standard IC. The primary end point was time to radiological PSH, and secondary outcomes included clinical PSH with/without surgical intervention and mesh-related complications. RESULTS: The 2 arms were similar in terms of baseline clinical features. All surgeries and mesh placements were performed without any intraoperative complications. Median operative time was 31 minutes longer in patients who received mesh, yet with no statistically significant difference (363 vs 332 minutes, P = .16). With a median follow-up of 24 months, radiological and clinical PSHs were detected in 37 (18 mesh recipients vs 19 controls) and 16 (8 subjects in both arms) patients, with a median time to radiological and clinical PSH of 8.3 and 15.5 months, respectively. No definite mesh-related adverse events were reported. Five patients (3 in the mesh and 2 in the control arm) required surgical PSH repair. Radiological PSH-free survival rates in the mesh and control groups were 74% vs 75% at 1 year and 69% vs 62% at 2 years. CONCLUSIONS: Implementation of biologic mesh at the time of IC construction is safe without significant protective effects within 2 years following surgery.
Assuntos
Cistectomia , Telas Cirúrgicas , Derivação Urinária , Humanos , Telas Cirúrgicas/efeitos adversos , Masculino , Feminino , Derivação Urinária/métodos , Idoso , Pessoa de Meia-Idade , Cistectomia/métodos , Cistectomia/efeitos adversos , Hérnia Incisional/prevenção & controle , Neoplasias da Bexiga Urinária/cirurgia , Seguimentos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Profiláticos/métodosRESUMO
BACKGROUND: Chest wall tumors are a heterogeneous group of tumors that are managed by surgeons from diverse specialties. Due to their rarity, there is no consensus on their diagnosis and management. MATERIALS: This retrospective, descriptive analysis includes patients with malignant chest wall tumors undergoing chest wall resection. Tumors were classified as primary, secondary, and metastatic tumors. The analysis includes clinicopathological characteristics, resection-reconstruction profile, and relapse patterns. RESULTS: A total of 181 patients underwent chest wall resection between 1999 and 2020. In primary tumors (69%), the majority were soft tissue tumors (59%). In secondary tumors, the majority were from the breast (45%) and lung (42%). Twenty-five percent of patients received neoadjuvant chemotherapy, and 98% of patients underwent R0 resection. Soft tissue, skeletal + soft tissue, and extended resections were performed in 45%, 70%, and 28% of patients, respectively. The majority of patients (60%) underwent rib resections, and a median of 3.5 ribs were resected. The mean defect size was 24 cm2. Soft tissue reconstruction was performed in 40% of patients, mostly with latissimus dorsi flaps. Rigid reconstruction was performed in 57% of patients, and 18% underwent mesh-bone cement sandwich technique reconstruction. Adjuvant radiotherapy and chemotherapy were given to 29% and 39% of patients, respectively. CONCLUSIONS: This is one of the largest single-institutional experiences on malignant chest wall tumors. The results highlight varied tumor spectra and multimodality approaches for optimal functional and survival outcomes. In limited resource setting, surgery, including reconstructive expertise, is very crucial.
Assuntos
Procedimentos de Cirurgia Plástica , Neoplasias Torácicas , Parede Torácica , Humanos , Parede Torácica/patologia , Parede Torácica/cirurgia , Feminino , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Neoplasias Torácicas/patologia , Neoplasias Torácicas/terapia , Neoplasias Torácicas/cirurgia , Idoso , Adulto , Prognóstico , Seguimentos , Neoplasias de Tecidos Moles/terapia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Adulto Jovem , Taxa de Sobrevida , Idoso de 80 Anos ou mais , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Recidiva Local de Neoplasia/cirurgia , Adolescente , Retalhos CirúrgicosRESUMO
Dissimilatory iron reduction (DIR) can drive the release of organic carbon (OC) as carbon dioxide (CO2 ) by mediating electron transfer between organic compounds and microbes. However, DIR is also crucial for carbon sequestration, which can affect inorganic-carbon redistribution via iron abiotic-phase transformation. The formation conditions of modern carbonate-bearing iron minerals (ICFe ) and their potential as a CO2 sink are still unclear. A natural environment with modern ICFe , such as karst lake sediment, could be a good analog to explore the regulation of microbial iron reduction and sequential mineral formation. We find that high porosity is conducive to electron transport and dissimilatory iron-reducing bacteria activity, which can increase the iron reduction rate. The iron-rich environment with high calcium and OC can form a large sediment pore structure to support rapid DIR, which is conducive to the formation and growth of ICFe . Our results further demonstrate that the minimum DIR threshold suitable for ICFe formation is 6.65 µmol g-1 dw day-1 . DIR is the dominant pathway (average 66.93%) of organic anaerobic mineralization, and the abiotic-phase transformation of Fe2+ reduces CO2 emissions by ~41.79%. Our findings indicate that as part of the carbon cycle, DIR not only drives mineralization reactions but also traps carbon, increasing the stability of carbon sinks. Considering the wide geographic distribution of DIR and ICFe , our findings suggest that the "iron mesh" effect may become an increasingly important vector of carbon sequestration.
Assuntos
Sequestro de Carbono , Ferro , Ferro/química , Ferro/metabolismo , Dióxido de Carbono , Oxirredução , Ciclo do Carbono , Compostos Férricos/metabolismoRESUMO
BACKGROUND: Veterans face high risk for HIV and substance use, and thus could be disproportionately impacted by the HIV and substance use disorder (SUD) "syndemic." HIV prevalence among veterans with SUD is unknown. OBJECTIVE: To project HIV prevalence and lifetime HIV screening history among US veterans with alcohol use disorder (AUD), opioid use disorder (OUD), or both. DESIGN: We conducted a retrospective cohort analysis using national Veterans Health Administration (VHA) data. PARTICIPANTS: We selected three cohorts of veterans with SUD: (1) AUD, (2) OUD, and (3) AUD/OUD. Included veterans had ICD codes for AUD/OUD from 2016 to 2022 recorded in VHA electronic medical records, sourced from the VA Corporate Data Warehouse (CDW). MAIN MEASURES: We estimated HIV prevalence by dividing the number of veterans who met two out of three criteria (codes for HIV diagnosis, antiretroviral therapy, or HIV screening/monitoring) by the total number of veterans in each cohort. We also estimated lifetime HIV screening history (as documented in VHA data) by cohort. We reported HIV prevalence and screening history by cohort and across demographic/clinical subgroups. KEY RESULTS: Our sample included 669,595 veterans with AUD, 63,787 with OUD, and 57,015 with AUD/OUD. HIV prevalence was highest in the AUD/OUD cohort (3.9%), followed by the OUD (2.1%) and AUD (1.1%) cohorts. Veterans of Black race and Hispanic/Latinx ethnicity, with HCV diagnoses, and aged 50-64 had the highest HIV prevalence in all cohorts. Overall, 12.8%, 29.1%, and 33.1% of the AUD/OUD, OUD, and AUD cohorts did not have history of HIV screening, respectively. CONCLUSIONS: HIV prevalence was high in all SUD cohorts, and was highest among veterans with AUD/OUD, with disparities by race/ethnicity and age. A substantial portion of veterans had not received HIV screening in the VHA. Findings highlight room for improvement in HIV prevention and screening services for veterans with SUD.
Assuntos
Alcoolismo , Infecções por HIV , Transtornos Relacionados ao Uso de Opioides , Transtornos Relacionados ao Uso de Substâncias , Veteranos , Estados Unidos/epidemiologia , Humanos , Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Prevalência , Analgésicos Opioides , Estudos Retrospectivos , United States Department of Veterans Affairs , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologiaRESUMO
BACKGROUND: Patient-physician sex discordance (when patient sex does not match physician sex) has been associated with reduced clinical rapport and adverse outcomes including post-operative mortality and unplanned hospital readmission. It remains unknown whether patient-physician sex discordance is associated with "before medically advised" hospital discharge (BMA discharge; commonly known as discharge "against medical advice"). OBJECTIVE: To evaluate whether patient-physician sex discordance is associated with BMA discharge. DESIGN: Retrospective cohort study using 15 years (2002-2017) of linked population-based administrative health data for all non-elective, non-obstetrical acute care hospitalizations from British Columbia, Canada. PARTICIPANTS: All individuals with eligible hospitalizations during study interval. MAIN MEASURES: Exposure: patient-physician sex discordance. OUTCOMES: BMA discharge (primary), 30-day hospital readmission or death (secondary). RESULTS: We identified 1,926,118 eligible index hospitalizations, 2.6% of which ended in BMA discharge. Among male patients, sex discordance was associated with BMA discharge (crude rate, 4.0% vs 2.9%; adjusted odds ratio [aOR] 1.08; 95%CI 1.03-1.14; p = 0.003). Among female patients, sex discordance was not associated with BMA discharge (crude rate, 2.0% vs 2.3%; aOR 1.02; 95%CI 0.96-1.08; p = 0.557). Compared to patient-physician sex discordance, younger patient age, prior substance use, and prior BMA discharge all had stronger associations with BMA discharge. CONCLUSIONS: Patient-physician sex discordance was associated with a small increase in BMA discharge among male patients. This finding may reflect communication gaps, differences in the care provided by male and female physicians, discriminatory attitudes among male patients, or residual confounding. Improved communication and better treatment of pain and opioid withdrawal may reduce BMA discharge.
RESUMO
The genetic overlap between schizophrenia (SZ) and bipolar disorder (BD) is substantial. Polygenic risk scores have been shown to dissect different symptom dimensions within and across these two disorders. Here, we focused on the most strongly associated SZ risk locus located in the extended MHC region, which is largely explained by copy numbers of the gene coding for complement component 4A (C4A). First, we utilized existing brain tissue collections (N = 1,202 samples) and observed no altered C4A expression in BD samples. The generated C4A seeded co-expression networks displayed no genetic enrichment for BD. To study if genetically predicted C4A expression discriminates between subphenotypes of BD, we applied C4A expression scores to symptom dimensions in a total of 4,739 BD cases with deep phenotypic data. We identified a significant association between C4A expression and psychotic mood episodes in BD type 1 (BDI). No significant association was observed between C4A expression and the occurrence of non-affective psychotic episodes in BDI, the psychosis dimensions in the total BD sample, or any other subphenotype of BD. Overall, these results points to a distinct role of C4A in BD that is restricted to vulnerability for developing psychotic symptoms during mood episodes in BDI.
Assuntos
Transtorno Bipolar , Transtornos Psicóticos , Esquizofrenia , Humanos , Transtorno Bipolar/psicologia , Complemento C4a/genética , Complemento C4a/metabolismo , Transtornos Psicóticos/genética , Esquizofrenia/genética , Esquizofrenia/diagnóstico , Herança MultifatorialRESUMO
INTRODUCTION: Bleeding disorders (BDs) may influence health-related quality of life (HRQoL) in children and caregivers. Measuring HRQoL gives insight into domains requiring support and provides an opportunity to evaluate the effects of novel therapies. AIM: To gain insight in the current body of literature on HRQoL in children with BDs in order to identify knowledge gaps for research and further development of this field. METHODS: Scoping review. RESULTS: We included 53 articles, describing studies mainly performed in Europe and North-America (60.4%) and mostly within the last ten years. Only 32% studies included children <4 years. Almost all studies (47/53, 88.7%) were performed in boys with haemophilia, pooling haemophilia A and B (n = 21) and different disease severities (n = 20). Thirteen different generic and five disease-specific HRQoL-questionnaires were applied; all questionnaires were validated for haemophilia specifically. Six (11,3%) combined generic and disease-specific questionnaires. Self-reports were most frequently applied (40/53, 75.5%), sometimes combined with proxy and/or parent-reports (17/53, 32.1%). Eleven studies used a reference group (20.8%). Statistical analyses mostly consisted of mean and SD (77.4%). CONCLUSION: HRQoL-research is mainly performed in school-aged boys with haemophilia, treated in developed countries. Pitfalls encountered are the pooling of various BDs, subtypes and severities, as well as the application of multiple generic questionnaires prohibiting comparison of results. More attention is needed for broader study populations including other BDs, young children, feminine bleeding issues and platelet disorders, as well as the use of HRQoL as an effect-measurement tool for medical interventions, and more thorough statistical analysis.
Assuntos
Hemofilia A , Qualidade de Vida , Criança , Masculino , Humanos , Pré-Escolar , Europa (Continente) , Inquéritos e Questionários , AutorrelatoRESUMO
BACKGROUND: Midurethral slings are the gold standard for treating stress urinary incontinence, but their complications may raise concerns. Complications may differ by the approach used to place them. OBJECTIVE: This study aimed to compare serious complications and reoperations for recurrence after midurethral sling procedures when using the retropubic vs the transobturator route for female stress urinary incontinence. STUDY DESIGN: This analysis was of patients included in the French, multicenter VIGI-MESH register since February 2017 who received a midurethral sling for female stress urinary incontinence either by the retropubic or the transobturator route and excluded patients with single-incision slings. Follow-up continued until October 2021. Serious complications (Clavien-Dindo classification ≥ grade III) attributable to the midurethral sling and reoperations for recurrence were compared using Cox proportional hazard models including any associated surgery (hysterectomy or prolapse) and a frailty term to consider the center effect. Baseline differences were balanced by propensity score weighting. Analyses using the propensity score and Cox models were adjusted for baseline differences, center effect, and associated surgery. RESULTS: A total of 1830 participants received a retropubic sling and 852 received a transobturator sling in 27 French centers that were placed by 167 surgeons. The cumulative 2-year estimate of serious complications was 5.8% (95% confidence interval, 4.8-7.0) in the retropubic group and 2.9% (95% confidence interval, 1.9-4.3) in the transobturator group, that is, after adjustment, half of the retropubic group was affected (adjusted hazard ratio, 0.41; 95% confidence interval, 0.3-0.6). The cumulative 2-year estimate of reoperation for recurrence of stress urinary incontinence was 2.7% (95% confidence interval, 2.0-3.6) in the retropubic group and 2.8% (95% confidence interval, 1.7-4.2) in the transobturator group with risk for revision for recurrence being higher in the transobturator group after adjustment (adjusted hazard ratio, 1.9; 95% confidence interval, 1.2-2.9); this surplus risk disappeared after exclusion of the patients with a previous surgery for stress urinary incontinence. CONCLUSION: The transobturator route for midurethral sling placement is associated with a lower risk for serious complications but a higher risk for surgical reoperation for recurrence than the retropubic route. Despite the large number of surgeons involved, these risks were low. The data are therefore reassuring.
Assuntos
Slings Suburetrais , Incontinência Urinária por Estresse , Feminino , Humanos , Incontinência Urinária por Estresse/cirurgia , Incontinência Urinária por Estresse/etiologia , Slings Suburetrais/efeitos adversos , Telas Cirúrgicas , Procedimentos Cirúrgicos Urológicos/métodos , ReoperaçãoRESUMO
OBJECTIVES: To detail the history of synthetic mid-urethral slings (SMUSs) and fascial slings, their efficacy, associated complications, and changes to practice that have occurred after the issuing of the 2011 US Food and Drug Administration (FDA) Safety Communication statement on transvaginal mesh (TVM), and to highlight the need for surgical registries and high-quality randomised controlled data to guide recommendations for continence procedures, in view of current concerns regarding mesh. METHODS: A literature search was conducted in EMBASE, PubMed, and the Cochrane Database of systematic reviews to identify articles published from 2011 onward, following the FDA Safety Communication regarding TVM. RESULTS: Prior to the formal FDA Safety Communication in 2011, TVM was considered a safe option for the treatment of both pelvic organ prolapse (POP) and stress urinary incontinence (SUI). The 2011 FDA safety communications and ensuing widely publicised litigation against TVM manufacturers have shifted both surgeon and patient acceptance of mesh products. Several efforts by medical and government bodies have been made to establish ways to monitor the surgical outcomes and safety of mesh products. The Australasian Pelvic Floor Procedure Registry is one such example. Although SMUSs have a long and established safety profile, perceptions of mesh products for SUI have also been negatively affected. The extent of this, however, has yet to be adequately measured through qualitative and quantitative data. The available data suggest it has been difficult for patients and consumers to distinguish between TVM morbidity for POP vs SUI. Furthermore, there remains a lack of high-quality randomised or real-world registry data to definitively exclude the SMUS from the SUI treatment algorithm. Since SMUSs are a viable option for SUI treatment, the concept of a 'post-mesh world' remains contentious. CONCLUSION: Controversies surrounding SMUSs have changed the treatment landscape of SUI. Against the background of significant litigious action following the FDA warnings against mesh use, there has been significant reduction in the uptake of synthetic mesh products. Although there are ample data related to surgical outcomes and safety for both autologous fascial and retropubic SMUSs in carefully selected patients, informed consent and surgical training will be of paramount importance as newer synthetic materials reach clinical maturity.
Assuntos
Slings Suburetrais , Telas Cirúrgicas , Incontinência Urinária por Estresse , Humanos , Slings Suburetrais/efeitos adversos , Telas Cirúrgicas/efeitos adversos , Incontinência Urinária por Estresse/cirurgia , Feminino , Prolapso de Órgão Pélvico/cirurgia , Estados Unidos , United States Food and Drug AdministrationRESUMO
OBJECTIVE: To identify all post-BNT162b2 vaccination (BioNTech and Pfizer) events during the ensuing 12 months in patients with systemic lupus erythematosus (SLE) from the Immuno-Rheumatology Department at Cayetano Heredia Hospital's cohort, Lima, Perú. METHODS: A 12-month follow-up study was conducted from the first dose of immunization with the BNT162b2 vaccine, which was given between May and June 2021, to SLE patients from this cohort. RESULTS: The initial population was constituted by 100 patients (100 patients received the 1st dose, 90 the 2nd dose, and 85 the 3rd dose of this vaccine); 33 patients presented a SLE reactivation (flare), 9% (9/100) post 1st dose, 26.6% (24/90) post 2nd dose, and 16.4% (14/85) post 3rd dose. The most common types of flare were articular (26) and renal (14) with 5/33 (15.1%) requiring hospitalization for flare management. A negative association with flare occurrence was found between the use of hydroxychloroquine RR 0.43 (0.21-0.85) and the opposite was the case for azathioprine RR 2.70 (1.39-5.25). During follow-up, 26 patients developed SARS-CoV-2 infection of whom three required hospitalization, one of whom died. CONCLUSIONS: 33 of 100 SLE patients immunized with BNT162b2 vaccine against SARS-CoV-2, presented SLE flares (47 episodes in total); 5 of these patients required in-hospital management and all fully recovered; 26 patients had SARS-CoV-2 infection; three required hospitalization, one died.
Assuntos
COVID-19 , Lúpus Eritematoso Sistêmico , Humanos , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Seguimentos , Imunização , Lúpus Eritematoso Sistêmico/tratamento farmacológico , SARS-CoV-2 , VacinaçãoRESUMO
OBJECTIVE: Vaccination against SARS-CoV-2 reduced morbidity and mortality rates due to COVID-19 worldwide. However, several adverse effects have been documented and of great interest such as Systemic Lupus Erythematosus (SLE). The aim of the present study was to perform a systematic review of case reports and case series describing the development of SLE following COVID-19 against vaccination. METHODS: Case report and case series studies were included. Systematic reviews, narratives, letters to the editor, correspondence, etc. were excluded. A selective bibliographic search was performed in the PubMed, Scopus, and EMBASE databases. In addition, the Web of Science platform was consulted. The Joanna Brigs Institute (JBI) tool was used to assess the risk of bias and quality of the studies. The Statistical Package for the Social Sciences (SPSS) 23.0 was used for the formal analysis of the descriptive data. RESULTS: 12 studies met the eligibility criteria and reported a total of 16 patients. The mean age was 42.4 ± 18.69 years. A slight predominance of post-vaccination SLE was observed in females (females (n = 9) and males (n = 7). A higher association was found with Pfizer-BioNTech-162b2 vaccine (75%), followed by Sinopharm (12.5%), Moderna (6.25%). and AstraZeneca (6.25%) vaccines. Most cases were associated with the first dose (56.25%), followed by the second dose (37.5%) and only one case associated with the third dose. The number of days elapsed from vaccine administration to the appearance of the first clinical manifestations was between 1 and 30 days. Mainly there was involvement of the musculoskeletal and cutaneous system. All patients responded well to treatment with good evolution and there was no case of death. CONCLUSION: Cases of SLE associated with COVID-19 vaccination against are infrequent. However, clinical monitoring is recommended for persons receiving the SARS-CoV-2 vaccine, mainly those receiving the first dose and the Pfizer-BioNTech-162b2 vaccine.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Lúpus Eritematoso Sistêmico , Humanos , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Vacinação/efeitos adversos , SARS-CoV-2 , Vacina BNT162/efeitos adversosRESUMO
PURPOSE: To report perioperative and long-term postoperative outcomes of cystectomy patients with ileal conduit (IC) urinary diversion undergoing parastomal hernia (PSH) repair. METHOD: We reviewed patients who underwent cystectomy and IC diversion between 2003 and 2022 in our center. Baseline variables, including surgical approach of PSH repair and repair technique, were captured. Multivariable Cox regressionanalysis was performed to test for the associations between different variables and PSH recurrence. RESULTS: Thirty-six patients with a median (IQR) age of 79 (73-82) years were included. The median time between cystectomy and PSH repair was 30 (14-49) months. Most PSH repairs (32/36, 89%) were performed electively, while 4 were due to small bowel obstruction. Hernia repairs were performed through open (n=25), robotic (10), and laparoscopic approaches (1). Surgical techniques included direct repair with mesh (20), direct repair without mesh (4), stoma relocation with mesh (5), and stomarelocation without mesh (7). The 90-day complication rate was 28%. In a median follow-up of 24 (7-47) months, 17 patients (47%) had a recurrence. The median time to recurrence was 9 (7-24) months. On multivariable analysis, 90-day complication following PSH repair was associated with an increased risk of recurrence. CONCLUSIONS: In this report of one of the largest series of PSH repair in the Urology literature, 47% of patients had a recurrence following hernia repair with a median follow-up time of 2 years. There was no significant difference in recurrence rates when comparing repair technique or the use of open or minimally invasive approaches.
Assuntos
Cistectomia , Herniorrafia , Hérnia Incisional , Derivação Urinária , Humanos , Derivação Urinária/métodos , Idoso , Masculino , Cistectomia/métodos , Feminino , Herniorrafia/métodos , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Resultado do Tratamento , Hérnia Incisional/cirurgia , Hérnia Incisional/etiologia , Hérnia Incisional/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Hérnia Ventral/cirurgia , Recidiva , Telas Cirúrgicas , Neoplasias da Bexiga Urinária/cirurgia , Fatores de TempoRESUMO
PURPOSE: To review our 10-year experience with laser excision for urethral mesh erosion (UME) of mid-urethral slings (MUS). METHODS: Following Institutional Review Board approval, the charts of female patients with endoscopic laser excision of UME were retrospectively reviewed. Demographics, clinical presentation, surgical history, pre- and post-operative Urinary Distress Inventory-6 scores and quality of life ratings, operative reports, and outcomes were obtained from electronic medical records. UME cure was defined as no residual mesh on office cystourethroscopy 5-6 months after the final laser excision procedure. RESULTS: From 2011 to 2021, 23 patients met study criteria; median age was 56 (range 44-79) years. Twenty (87%) had multiple prior urogynecologic procedures. Median time from MUS placement to presentation with UME-related complaints was 5.3 [interquartile range (IQR) 2.3-7.6] years. The most common presenting symptom was recurrent urinary tract infection (rUTI) (n = 10). Median operating time was 49 (IQR 37-80) minutes. Median duration of follow-up was 24 (IQR 12-84) months. Fourteen (61%) required more than 1 laser excision procedure for UME. Although 5 were asymptomatic (22%), new (n = 5) or persistent (n = 8) urinary incontinence was the most common symptom on follow-up (57%). CONCLUSION: UME presenting symptoms are highly variable, necessitating a high index of suspicion in patients with a history of MUS, especially in the case of rUTI. Endoscopic laser excision is a minimally invasive, brief, safe, outpatient procedure with a high UME cure rate.