RESUMO
PURPOSE: To evaluate if self-administered bladder neuromodulation with transcutaneous tibial nerve stimulation can safely replace overactive bladder medications in people with spinal cord injury. MATERIALS AND METHODS: We performed a 3-month, randomized, investigator-blinded, tibial nerve stimulation vs sham-control trial in adults with spinal cord injury and neurogenic bladder performing intermittent catheterization and taking overactive bladder medications. The primary outcome was a reduction in bladder medications while maintaining stable bladder symptoms and quality of life based on pre-post Neurogenic Bladder Symptom Score and the Incontinence-QOL questionnaire, respectively. Secondary outcomes included changes in pre-post cystometrogram, 2-day voiding diaries, and an anticholinergic medication side effect survey. RESULTS: Fifty people consented to the study, with 42 completing the trial. No dropouts were due to stimulation issues. All baseline demographics and surveys were comparable at baseline. Cystometrogram parameters were also comparable at baseline, except the stimulation group had a higher proportion of loss of bladder compliance compared to the control group. At the end of the trial, a significantly greater percentage of the tibial nerve stimulation group were able to reduce medications (95% v 68%), by a 26.2% difference in medication reduction (95% confidence interval 1.17%-51.2%). Function and quality of life surveys and cystometrograms at the end of the trial were alike between groups. Transcutaneous tibial nerve stimulation satisfaction surveys and adherence to protocol were high. CONCLUSIONS: In people with chronic spinal cord injury performing intermittent catheterization, transcutaneous tibial nerve stimulation can be an option to reduce or replace overactive bladder medications.
RESUMO
Objective: To determine the magnitude of the perioperative costs associated with robotic gastrectomy (RG). Background: A robotic surgery platform has a high implementation cost and requires maintenance costs; however, whether the overall cost of RG, including all perioperative costs, is higher than conventional open gastrectomy (OG) remains unknown. Methods: Patients who underwent a major gastrectomy during February 2018 through December 2021 were retrospectively identified. We calculated the perioperative costs of RG and OG and compared them overall as well as in different phases, including intraoperative costs and 30-day postsurgery inpatient and outpatient costs. We investigated factors potentially associated with high cost and estimated the likelihood of RG to reduce overall cost under a Bayesian framework. All cost data were converted to ratios to the average cost of all operations performed at our center in year FY2021. Results: We identified 119 patients who underwent gastrectomy. The incidence of postoperative complications (Clavien-Dindo >IIIa; RG, 10% vs OG, 13%) did not significantly differ between approaches. The median length of stay was 3 days shorter for RG versus OG (4 vs 7 days, P < 0.001). Intraoperative cost ratios were significantly higher for RG (RG, 2.6 vs OG, 1.7; P < 0.001). However, postoperative hospitalization cost ratios were significantly lower for RG (RG, 2.8 vs OG, 3.9; P < 0.001). Total perioperative cost ratios were similar between groups (RG, 6.1 vs OG, 6.4; P = 0.534). The multiple Bayesian generalized linear analysis showed RG had 76.5% posterior probability of overall perioperative cost reduction (adjusted risk ratio of 0.95; 95% credible interval, 0.85-1.07). Conclusions: Despite increased intraoperative costs, total perioperative costs in the RG group were similar to those in the OG group because of reduced postoperative hospitalization costs.
RESUMO
OBJECTIVE: To identify urinary biomarkers that can distinguish active renal involvement in Lupus Nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE). METHODS: Urine from 117 subjects, comprised of inactive SLE, active non-renal lupus, active LN, and healthy controls, were subjected to Proximity Extension Assay (PEA) based comprehensive proteomics followed by ELISA validation in an independent, ethnically diverse cohort. Proteomic data is also cross-referenced to renal transcriptomic data to elucidate cellular origins of biomarkers. RESULTS: Systems biology analyses revealed progressive activation of cytokine signaling, chemokine activity and coagulation pathways, with worsening renal disease. In addition to validating 30 previously reported biomarkers, this study uncovers several novel candidates. Following ELISA validation in an independent cohort of different ethnicity, the six most discriminatory biomarkers for active LN were urinary ICAM-2, FABP4, FASLG, IGFBP-2, SELE and TNFSF13B/BAFF, with ROC AUC ≥80%, with most correlating strongly with clinical disease activity. Transcriptomic analyses of LN kidneys mapped the likely origin of these proteins to intra-renal myeloid cells (CXCL16, IL-1RT2, TNFSF13B/BAFF), T/NK cells (FASLG), leukocytes (ICAM2) and endothelial cells (SELE). CONCLUSION: In addition to confirming the diagnostic potential of urine ALCAM, CD163, MCP1, SELL, ICAM1, VCAM1, NGAL and TWEAK for active LN, this study adds urine ICAM-2, FABP4, FASLG, IGFBP-2, SELE, and TNFSF13B/BAFF as additional markers that warrant systematic validation in larger cross-sectional and longitudinal cohorts.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/genética , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina , Proteômica , Estudos Transversais , Células Endoteliais , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/genética , Biomarcadores , Rim , Perfilação da Expressão GênicaRESUMO
OBJECTIVES: To describe and analyze the trends of pediatric sinusitis cases from 2018 to 2022 across the country utilizing the Pediatric Hospital Information System (PHIS) database focusing on volumes, socioeconomics, and severity of cases. STUDY DESIGN: Retrospective Cohort Study. METHODS: A retrospective cohort study using the Pediatric Health Information System (PHIS) database, which consists of 50 children's hospitals was performed. Regions were defined according to PHIS guidelines. We evaluated percentage of sinusitis cases demographic and socioeconomic information and subgrouped by region throughout 2018-2022. RESULTS: In all regions there were a greater number of sinusitis cases post-COVID compared to pre-COVID, with notable increases in major and extreme severity. The years 2020 and 2021 saw a decrease in total sinusitis cases in all locations. Both surgical intervention and severity of sinusitis were significant factors affecting length of stay. Age and severity were the most significant predictors regarding the odds of having sinus surgery. Age and insurance type were significant predictors of severity, with increasing age and government insurance associated with higher odds of major or extreme severity of sinusitis. CONCLUSIONS: There appears to be a trend of both increased number and worsening severity of acute sinusitis cases in the post-COVID era compared to pre-COVID. There was a decrease in cases in 2020-2021 during the pandemic, consistent with trends of other communicable diseases.
Assuntos
COVID-19 , Sinusite , Humanos , Criança , COVID-19/epidemiologia , Estudos Retrospectivos , Bases de Dados Factuais , Pandemias , Sinusite/epidemiologiaRESUMO
BACKGROUND: Two characteristics of commonly used outcomes in medical research are zero inflation and non-negative integers; examples include the number of hospital admissions or emergency department visits, where the majority of patients will have zero counts. Zero-inflated regression models were devised to analyze this type of data. However, the performance of zero-inflated regression models or the properties of data best suited for these analyses have not been thoroughly investigated. METHODS: We conducted a simulation study to evaluate the performance of two generalized linear models, negative binomial and zero-inflated negative binomial, for analyzing zero-inflated count data. Simulation scenarios assumed a randomized controlled trial design and varied the true underlying distribution, sample size, and rate of zero inflation. We compared the models in terms of bias, mean squared error, and coverage. Additionally, we used logistic regression to determine which data properties are most important for predicting the best-fitting model. RESULTS: We first found that, regardless of the rate of zero inflation, there was little difference between the conventional negative binomial and its zero-inflated counterpart in terms of bias of the marginal treatment group coefficient. Second, even when the outcome was simulated from a zero-inflated distribution, a negative binomial model was favored above its ZI counterpart in terms of the Akaike Information Criterion. Third, the mean and skewness of the non-zero part of the data were stronger predictors of model preference than the percentage of zero counts. These results were not affected by the sample size, which ranged from 60 to 800. CONCLUSIONS: We recommend that the rate of zero inflation and overdispersion in the outcome should not be the sole and main justification for choosing zero-inflated regression models. Investigators should also consider other data characteristics when choosing a model for count data. In addition, if the performance of the NB and ZINB regression models is reasonably comparable even with ZI outcomes, we advocate the use of the NB regression model due to its clear and straightforward interpretation of the results.
Assuntos
Modelos Estatísticos , Telemedicina , Humanos , Criança , Simulação por Computador , Modelos Lineares , ViésRESUMO
RNA-based therapeutics and vaccines are opening up new avenues for modern medicine. To produce these useful RNA-based reagents, in vitro transcription (IVT) is an important reaction that primarily determines the yield and quality of the product. Therefore, IVT condition should be well optimized to achieve high yield and purity of transcribed RNAs. To this end, real-time monitoring of RNA production during IVT, which allows for fine tuning of the condition, would be required. Currently, light-up RNA aptamer and fluorescent dye pairs are considered as useful strategies to monitor IVT in real time. Fluorophore-labeled antisense probe-based methods can also be used for real-time IVT monitoring. In addition, a high-performance liquid chromatography (HPLC)-based method that can monitor IVT reagent consumption has been developed as a powerful tool to monitor IVT reaction in near real-time. This mini-review briefly introduces some strategies and examples for real-time IVT monitoring and discusses pros and cons of IVT monitoring methods.
RESUMO
Circular RNA (circRNA) has various advantages over linear mRNA that is gaining success as a new vaccine and therapeutic agent. Thus, circRNA and its engineering methods have attracted attention recently. In this study, we developed a new in vitro circRNA engineering method by end-to-end self-targeting and splicing (STS) reaction using Tetrahymena group I intron ribozyme. We found that only the P1 helix structure of the group I intron was enough to generate circRNA by STS reaction. The efficacy of circRNA generation by STS reaction was comparable to the method using a permuted intron-exon (PIE) reaction. However, an end-to-end STS reaction does not introduce any extraneous fragments, such as an intronic scar that can be generated by PIE reaction and might trigger unwanted innate immune responses in cells, into circRNA sequences. Moreover, generated circRNA was efficiently purified by ion pair-reversed phase high-pressure liquid chromatography and used for cell-based analysis. Of note, efficient protein expression and stability with least innate immune induction by the circRNA with coxsackievirus B3 IRES were observed in cells. In conclusion, our new in vitro circRNA strategy can effectively generate highly useful circRNAs in vitro as an alternative circRNA engineering method.
RESUMO
Background: In the porcine industry, Escherichia coli (E. coli) infections have been causing post-weaning diarrhea (PWD) and edema disease (ED) for many years. It is classified into pathotypes and serotypes in animals according to virulence factors. Serotyping is performed for O, K, H, and F antigens, essential for discriminating pathogenicity and epidemiology. Furthermore, E. coli strains that produce F18 fimbriae are major sources of ED and PWD associated with Shiga-toxin producing E. coli (STEC) expressing F18ab and enterotoxigenic E. coli (ETEC) expressing F18ac, respectively. Aim: To investigate the pathogenicity potential and infection characteristics of experimental infection and confirm the pathological features of the Korean STEC/ETEC strains F18ab and F18ac in piglets. Methods: Three-week-old pigs were randomized into three experimental groups: infected G1 (F18ab), infected G2 (F18ac), and G3 (control). General health status was monitored daily, and pathological changes were evaluated. Results: Diarrhea occurred in all infected piglets. Pathological changes were only observed in the small intestine and regional lymph nodes. In G1, mucosal necrosis, inflammatory cell infiltration with hemorrhagic lesions, and apoptotic cell death in the tunica media of arterioles in the small intestine were observed. In contrast, the mucosa and epithelium appeared almost intact, with no abnormal vessel lesions in G2. Conclusion: Both strains, isolated from pigs in Korea, could be infected and did not spread from the alimentary tract to other organs. The pathological features were quite different among the F18 subtypes. The F18ab strain was more virulent than F18ac, and the virulence characteristics of the F18ac strain were more similar to ETEC than STEC.
Assuntos
Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Escherichia coli Shiga Toxigênica , Doenças dos Suínos , Animais , Diarreia/veterinária , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/veterinária , Fezes , República da Coreia/epidemiologia , Suínos , Doenças dos Suínos/epidemiologiaRESUMO
Background: Biologic mesh has been used increasingly in complex ventral hernia repair despite limited evidence at low risk of bias supporting its use. Patients and Methods: We performed a participant-level analysis of published randomized controlled trials (RCTs) comparing biologic to synthetic mesh with complex ventral hernia repair at 24 to 36 months. Primary outcome was major complication (composite of mesh infection, recurrence, reoperation, or death) at 24 to 36 months post-operative. Secondary outcomes included length of index hospital stay, surgical site occurrence, surgical site infection, and death. Outcomes were assessed using both frequentist and Bayesian generalized linear regression models. Results: A total of 252 patients from two RCTs were included, 126 patients randomized to the intervention arm of biologic and 126 patients to the control of synthetic mesh with median follow-up of 29 (23, 38) months. Major complication occurred in 33 (33%) patients randomized to biologic, and 39 (38%) patients randomized to synthetic mesh, (relative risk [RR] 0.91, 95% confidence interval [CI] 0.63-1.31; p value = 0.600). Bayesian analysis demonstrated that compared with synthetic mesh, biologic mesh had similar probability of major complications at 24 to 36 months post-operative. The remainder of outcomes demonstrated slight benefit with synthetic mesh as opposed to biologic mesh except for mesh infection. However, under a frequentist framework, no outcome was statistically different. Conclusions: In patients undergoing open ventral hernia repair, there was no benefit for patients receiving biologic versus synthetic mesh at 24 to 36 months post-operative.
Assuntos
Produtos Biológicos , Hérnia Ventral , Humanos , Telas Cirúrgicas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Hérnia Ventral/cirurgia , Infecção da Ferida Cirúrgica/etiologia , Herniorrafia/efeitos adversos , Resultado do Tratamento , Recidiva , Estudos RetrospectivosRESUMO
BACKGROUND: Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. METHODS: An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. RESULTS: Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine D-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75-0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. CONCLUSIONS: Given the high sensitivity (97%) of urine D-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test.
Assuntos
Proteômica , Neoplasias da Bexiga Urinária , Masculino , Humanos , Interleucina-8 , Biomarcadores Tumorais/urina , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Bexiga Urinária/diagnóstico , Progressão da Doença , Imunoglobulina ARESUMO
INTRODUCTION: Cochlear Implants (CI) are a mainstay in the treatment of severe sensorineural hearing loss with proven cost-effectiveness and improved quality of life. However, costs associated with CI are variable. During the Covid-19 pandemic, elective surgeries decreased. The investigation into how the pandemic affected CI procedures, costs, and demographic utilization has not been elucidated. METHODS: A retrospective cohort study using the Pediatric Health Information System® (PHIS) database, which consists of 50 children's hospitals, was performed. Regions were defined according to PHIS guidelines. We evaluated number of CIs, total charges and costs, Charge to Cost Ratios (CCR), demographic information, and subgrouped this analysis by region throughout 2016-2021. Charges were adjusted by CMS wage index for hospital location. RESULTS: During the years of 2016-2021, there was a rising number of CIs every year except for 2020 which had a decrease, largely driven by the southern and midwestern regions. The median number of cases did not differ between the years. The median adjusted charges increased every year, but not significantly ($103,883-$125,394). The median CCR also did not differ throughout the years (2.7-3.1). Still, there was a larger interquartile range in 2021 (2.3-4.4) for the median CCR compared to all other years (2.1-3.8), particularly in the South. The percentage of white, non-Hispanic/Latino patients who underwent CI was larger in 2020-2021 (78-79.8 %) compared to 2016-2019 (73.3-77.5 %). CONCLUSIONS: The number of CIs in 2020 was lower than in 2019 or 2021. The median CCR for CI procedures increased from 2016 to 2021 but not significantly. The range of CCR was larger in 2021 compared to the years prior, suggestive of cost shifting by some hospitals to offset the loss in revenue. There was a small but significant increase in white, non-Hispanic patients receiving CI in 2020 and 2021, suggestive of a socio-economic shift in care post pandemic.
Assuntos
COVID-19 , Implante Coclear , Implantes Cocleares , Criança , Humanos , Implante Coclear/métodos , Qualidade de Vida , Pandemias , Estudos Retrospectivos , Análise Custo-Benefício , Anos de Vida Ajustados por Qualidade de Vida , COVID-19/epidemiologiaRESUMO
mRNA is gaining success as a new therapeutic agent and vaccine. However, mRNA has limitations in stability. To overcome the shortcomings of mRNA, circular RNA is emerging as a new modality. In this review, several current methods of manufacturing circular RNA in vitro are introduced and their advantages and disadvantages are reviewed. Furthermore, this study discusses which fields and directions of research and development are needed for the increase in the efficacy and productivity of circular RNA as a therapeutic agent and vaccine formulation.
Assuntos
RNA Circular , RNA , RNA Mensageiro/genética , Técnicas In Vitro , RNA/genéticaRESUMO
Adulteration and mislabeling of honey to mask its true origin have become a global concern. Pollen microscopy, the current gold standard for identifying honey's geographical and plant origins, is laborious, requires extensive training, and fails to identify filtered honey and honey spiked with pollen from a more favorable plant to disguise its origins. We successfully isolated pollen-free DNA from filtered honey using three types of adsorbents: (i) anti-dsDNA antibodies coupled to magnetic microspheres; (ii) anion-exchange adsorbent; and (iii) ceramic hydroxyapatite. The internal transcribed spacer 2 region of the captured pollen-free DNA was polymerase chain reaction-amplified and subjected to next-generation sequencing. Using an in-house bioinformatics pipeline, initial experiments showed that anion exchange had the greatest capacity to capture trace pollen-free DNA, and it was successfully applied to isolate DNA from five honey samples. Enrichment of trace pollen-free DNA from filtered honey samples opens a new approach for identifying the true origins of honey.
Assuntos
Mel , Mel/análise , Pólen/genética , Código de Barras de DNA Taxonômico , DNARESUMO
BACKGROUND: The relationship of specific body composition in the thighs and brain amyloid-beta (Aß) deposition remained unclear, although there were growing evidence that higher muscle and fat mass in thighs had a protective effect against cardiometabolic syndromes. To determine whether muscle mass and fat mass in the thighs affected amyloid-beta (Aß) positivity differently in relation to gender, we investigated the association of muscle mass and fat mass with Aß positivity using positron emission tomography (PET) in individuals without dementia. METHODS: We recruited 240 participants (134 [55.8%] males, 106 [44.2%] females) without dementia ≥45 years of age who underwent Aß PET, bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DEXA) scans of the hip in the health promotion center at Samsung Medical Center in Seoul, Korea. Lower extremity skeletal muscle mass index (LASMI) was measured using BIA, and gluteofemoral fat percentage (GFFP) was estimated using DEXA scans of the hip. We investigated the associations of LASMI and GFFP with Aß positivity using logistic regression analyses after controlling for age, APOE4 genotype, and cognitive stage. RESULTS: Higher muscle mass in the thighs, measured as LASMI (odds ratio [OR]=0.27, 95% confidence interval [CI] 0.08 to 0.84, p=0.031) was associated with a lesser risk of Aß positivity in only females. Higher fat mass in the thighs, measured as GFFP (OR=0.84, 95% CI 0.73 to 0.95, p=0.008) was associated with a lesser risk of Aß positivity in only males. However, the association between LAMSI (p for interaction= 0.810), GFFP (p for interaction= 0.075) and Aß positivity did not significantly differ by gender. Furthermore, LAMSI only negatively correlated with centiloid (CL) values in females (r=-0.205, p=0.037), and GFFP only negatively correlated with CL values only in males (r=-0.253, p=0.004). CONCLUSIONS: Our findings highlight the importance of recognizing that gender differences exist with respect to the specific body composition to potentially protect against Aß deposition. Therefore, our results may help in designing gender-specific strategies for controlling body composition to prevent Aß deposition.
Assuntos
Apolipoproteína E4 , Demência , Peptídeos beta-Amiloides/metabolismo , Apolipoproteína E4/genética , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Feminino , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/metabolismo , Tomografia por Emissão de Pósitrons , Coxa da Perna/diagnóstico por imagemRESUMO
Accurate prediction of postoperative mortality is important for not only successful postoperative patient care but also for information-based shared decision-making with patients and efficient allocation of medical resources. This study aimed to create a machine-learning prediction model for 30-day mortality after a non-cardiac surgery that adapts to the manageable amount of clinical information as input features and is validated against multi-centered rather than single-centered data. Data were collected from 454,404 patients over 18 years of age who underwent non-cardiac surgeries from four independent institutions. We performed a retrospective analysis of the retrieved data. Only 12-18 clinical variables were used for model training. Logistic regression, random forest classifier, extreme gradient boosting (XGBoost), and deep neural network methods were applied to compare the prediction performances. To reduce overfitting and create a robust model, bootstrapping and grid search with tenfold cross-validation were performed. The XGBoost method in Seoul National University Hospital (SNUH) data delivers the best performance in terms of the area under receiver operating characteristic curve (AUROC) (0.9376) and the area under the precision-recall curve (0.1593). The predictive performance was the best when the SNUH model was validated with Ewha Womans University Medical Center data (AUROC, 0.941). Preoperative albumin, prothrombin time, and age were the most important features in the model for each hospital. It is possible to create a robust artificial intelligence prediction model applicable to multiple institutions through a light predictive model using only minimal preoperative information that can be automatically extracted from each hospital.
RESUMO
OBJECTIVES/HYPOTHESIS: To determine the effects of the COVID-19 pandemic on Adenotonsillectomies (TA), Tonsil Related Cases (TC), and Peritonsillar Abscess (PTA) Trends. STUDY DESIGN: Retrospective Cohort Study. METHODS: This is a retrospective cohort study using the Pediatric Health Information System® (PHIS) database, which consists of 51 children's hospitals. Regions were defined according to PHIS rules with at least five children's hospitals per region. We compared monthly total TA, TC, TC as a proportion of all hospital visits, and PTA from all encounters at each hospital from January 1, 2019, through December 31, 2021. RESULTS: Compared to 2019, April 2020 saw mean TC drop significantly from 371.62 to 68.37 (p < 0.001). Interestingly, June, September, and December 2020 had significantly higher mean TC compared to 2019. TC as a proportion of all hospital visits decreased significantly throughout the majority of 2021. Similarly, TA significantly decreased during 2020 and 2021 across all regions in the US, starting in March 2020 and this reduction in TA extended through the end of 2021 without any signs of recovery. PTA rates did not change significantly over the three years. CONCLUSIONS: The pandemic-plagued 2020 saw a noticeable decrease in overall TC and TA but then rebounded quickly to even higher than pre-pandemic levels. However, this rebound halted for the majority of 2021 and subsequently decreased to lower than pre-pandemic levels, which differs from other communicable pathologies such as otitis media which decreased initially then recovered to pre-pandemic levels by Summer of 2021.
Assuntos
COVID-19 , Otolaringologia , Abscesso Peritonsilar , COVID-19/epidemiologia , Criança , Humanos , Tonsila Palatina , Pandemias , Abscesso Peritonsilar/diagnóstico , Abscesso Peritonsilar/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: The endotheliopathy of trauma (EoT) is associated with increased mortality following injury. Herein, we describe the plasma proteome related to EoT in order to provide insight into the role of the endothelium within the systemic response to trauma. METHODS: 99 subjects requiring the highest level of trauma activation were included in the study. Enzyme-linked immunosorbent assays of endothelial and catecholamine biomarkers were performed on admission plasma samples, as well as untargeted proteome quantification utilizing high-performance liquid chromatography and tandem mass spectrometry. RESULTS: Plasma endothelial and catecholamine biomarker abundance was elevated in EoT. Patients with EoT (n = 62) had an increased incidence of death within 24 h at 21% compared to 3% for non-EoT (n = 37). Proteomic analysis revealed that 52 out of 290 proteins were differentially expressed between the EoT and non-EoT groups. These proteins are involved in endothelial activation, coagulation, inflammation, and oxidative stress, and include known damage-associated molecular patterns (DAMPs) and intracellular proteins specific to several organs. CONCLUSIONS: We report a proteomic profile of EoT suggestive of a surge of DAMPs and inflammation driving nonspecific activation of the endothelial, coagulation, and complement systems with subsequent end-organ damage and poor clinical outcome. These findings support the utility of EoT as an index of cellular injury and delineate protein candidates for therapeutic intervention.
Assuntos
Proteoma , Proteômica , Biomarcadores , Catecolaminas , Humanos , Inflamação , Estudos ProspectivosRESUMO
Objectives: Serial kidney biopsy for repeat evaluation and monitoring of lupus nephritis (LN) in childhood-onset Systemic Lupus Erythematosus (cSLE) remains challenging, thus non-invasive biomarkers are needed. Here, we evaluate the performance of ten urine protein markers of diverse nature including cytokines, chemokines, and adhesion molecules in distinguishing disease activity in cSLE. Methods: Eighty-four pediatric patients meeting ≥4 ACR criteria for SLE were prospectively enrolled for urine assay of 10 protein markers normalized to urine creatinine, namely ALCAM, cystatin-C, hemopexin, KIM-1, MCP-1, NGAL, PF-4, Timp-1, TWEAK, and VCAM-1 by ELISA. Samples from active renal (LN) and active non-renal SLE patients were obtained prior to onset/escalation of immunosuppression. SLE disease activity was evaluated using SLEDAI-2000. 59 patients had clinically-active SLE (SLEDAI score ≥4 or having a flare), of whom 29 patients (34.5%) were classified as active renal, and 30 patients (35.7%) were active non-renal. Twenty-five healthy subjects were recruited as controls. Results: Urine concentrations of ALCAM, KIM-1, PF4 and VCAM-1 were significantly increased in active LN patients versus active non-renal SLE, inactive SLE and healthy controls. Five urine proteins differed significantly between 2 (hemopexin, NGAL, MCP1) or 3 (Cystatin-C, TWEAK) groups only, with the highest levels detected in active LN patients. Urine ALCAM, VCAM-1, PF4 and hemopexin correlated best with total SLEDAI as well as renal-SLEDAI scores (p < 0.05). Urine ALCAM, VCAM-1 and hemopexin outperformed conventional laboratory measures (anti-dsDNA, complement C3 and C4) in identifying concurrent SLE disease activity among patients (AUCs 0.75, 0.81, 0.81 respectively), while urine ALCAM, VCAM-1 and PF4 were the best discriminators of renal disease activity in cSLE (AUCs 0.83, 0.88, 0.78 respectively), surpassing conventional biomarkers, including proteinuria. Unsupervised Bayesian network analysis based on conditional probabilities re-affirmed urine ALCAM as being most predictive of active LN in cSLE patients. Conclusion: Urinary ALCAM, PF4, and VCAM-1 are potential biomarkers for predicting kidney disease activity in cSLE and hold potential as surrogate markers of nephritis flares in these patients.
Assuntos
Cistatinas , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Molécula de Adesão de Leucócito Ativado , Antígenos CD , Teorema de Bayes , Benchmarking , Biomarcadores/urina , Moléculas de Adesão Celular Neuronais , Criança , Proteínas Fetais , Hemopexina , Humanos , Lipocalina-2 , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/diagnóstico , Fator Plaquetário 4 , Proteínas , Molécula 1 de Adesão de Célula VascularRESUMO
BACKGROUND AND AIMS: Whether subjects with NAFLD are at increased risk of sarcopenia is not well established. APPROACH AND RESULTS: This is a cohort study of 52,815 men and women of 20 years of age or older who underwent at least two health check-up exams with bioelectrical impedance analysis and abdominal ultrasound imaging. Bioelectrical impedance analysis was used to calculate appendicular skeletal muscle mass (ASM). NAFLD was assessed by ultrasonography, and its severity was assessed by the NAFLD fibrosis score (NFS). We estimated the 5-year change in ASM comparing participants with and without NAFLD at baseline using mixed linear models. The 5-year change in ASM in participants without and with NAFLD was -225.2 g (95% CI -232.3, -218.0) and -281.3 g (95% CI -292.0, -270.6), respectively (p < 0.001). In multivariable adjusted analysis, the difference in 5-year change in ASM comparing participants with and without NAFLD was -39.9 g (95% CI -53.1, -26.8). When participants with NAFLD were further divided by NAFLD severity, ASM loss was much faster in participants with NAFLD with intermediate to high NFS than in those with low NFS. CONCLUSIONS: Participants with NAFLD were at increased risk of sarcopenia, indicated by faster loss of skeletal muscle mass. Patients with NAFLD may need screening and early intervention to mitigate skeletal muscle mass loss.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Sarcopenia , Masculino , Humanos , Feminino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Sarcopenia/complicações , Sarcopenia/diagnóstico por imagem , Sarcopenia/patologia , Estudos de Coortes , Estudos Longitudinais , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologiaRESUMO
BACKGROUND: Achieving healthy vascular aging (HVA) is important for decelerating age-related cardiovascular disease risk. We evaluated the interplay between HVA, cardiorespiratory fitness (CRF), and subclinical atherosclerosis. METHODS: We analyzed data on 3722 men who underwent cardiopulmonary exercise testing in a health examination program. HVA was defined as blood pressure <140/90 mm Hg without hypertension and brachial-ankle pulse wave velocity <1266 cm/s. CRF was directly measured by peak oxygen uptake. Subclinical atherosclerosis was defined as coronary artery calcification scores of >0 and ≥100 and a mean carotid artery intima-media thickness (CIMT) >75th percentile for each age group as well as >0.8 mm of CIMT. Separate and joint associations of HVA and CRF with subclinical atherosclerosis were evaluated. RESULTS: Each 1 metabolic equivalent increment in CRF was associated with 23% higher odds for having HVA. HVA was associated with lower odds of coronary artery calcification but not CIMT. CRF modified the association between HVA and CIMT>0.8 mm (interaction: P=0.01); HVA was associated with lower odds of CIMT>0.8 mm in fit men with no significant association between HVA and CIMT>0.8 mm in unfit men. Compared with no HVA and being unfit, HVA and being fit was associated with lower odds of subclinical atherosclerosis, but there was no significant association between HVA and being unfit with subclinical atherosclerosis. CONCLUSIONS: HVA and higher CRF are each associated with a lower risk of subclinical atherosclerosis in men. Higher CRF is associated with a higher prevalence of HVA and may modify the association between HVA and subclinical atherosclerosis.