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1.
Mol Immunol ; 171: 47-55, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38795684

RESUMO

Myopia is regarded as a worldwide epidemic ocular disease, has been proved related to inflammation. CD55, also known as decay-accelerating factor (DAF) can modulate the activation of complement through inhibiting the formation of complement 3 convertase and its dysregulation is involved in various inflammatory diseases. To investigate the association between CD55 and myopia, and to test whether CD55 can inhibit myopia development by suppressing inflammation in the eye, we use three different animal models including monocular form-deprivation myopia, myopia induced by TNF-α administration and allergic conjunctivitis animal model to reveal the CD55 in myopia development. The tears of thirty-eight participants with different spherical equivalents were collected and CD55 in the tears were also analyzed. Complement 3 and complement 5 levels increased while CD55 levels decreased in allergic conjunctivitis and myopic eyes. After anti-inflammatory drugs administration, CD55 expression was increased in monocular form-deprivation myopia model. We also found inflammatory cytokines TGF-ß, IL-6, TNF-α, and IL-1ß may enhance complement 3 and complement 5 activation while CD55 level was suppressed contrary. Moreover, lower CD55 levels were found in the tears of patients with myopia with decreased diopter values. Finally, CD55-Fc administration on the eyelids can inhibit the elongation of axial length and change of refractive error. CD55-Fc application also suppress myopia development subsequent to complement 3 and complement 5 reduction and can lower myopia-specific (MMP-2 and TGF-ß) cytokine expression in TNF-α induced myopia animal model. This suggests that CD55 can inhibit myopia development by suppression of complement activation and eventual down-regulation of inflammation.


Assuntos
Antígenos CD55 , Modelos Animais de Doenças , Inflamação , Miopia , Adolescente , Animais , Feminino , Humanos , Masculino , Adulto Jovem , Antígenos CD55/metabolismo , Ativação do Complemento/efeitos dos fármacos , Complemento C3/metabolismo , Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/metabolismo , Citocinas/metabolismo , Miopia/metabolismo , Lágrimas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Complemento C5/metabolismo
2.
Mol Immunol ; 167: 34-42, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38340674

RESUMO

Myopia is widely recognized as an epidemic. Studies have found a link between Transforming Growth Factor-beta (TGF-ß) and myopia, but the specific molecular mechanisms are not fully understood. In this study, a monocular model in tree shrews (Tupaia belangeri) was established to verify the molecular mechanism of TGF-ß in myopia. The results indicated that there were significant changes in TGF-ßs during the treatment of myopia, which could enhance the refractive ability and axial length of the eye. Immunohistochemical staining, real-time fluorescent quantitative PCR, and immunoblotting results showed a significant upregulation of MMP2 and NF-κB levels, and a significant downregulation of COL-I expression in the TGF-ß treated eyes, suggesting that NF-κB and MMP2 are involved in the signaling pathways of TGF-ßs induced myopia and axial elongation. Moreover, the expression levels of IL-6, IL-8, MCP-1, IL-1ß, TNF-α, TAK1, and NF-κB in the retina were all significantly elevated. This indicates that TGF-ß stimulates the inflammatory response of retinal pigment epithelial cells through the TAK1-NF-κB signaling pathway. In conclusion, this study suggests that TGF-ß promotes the progression of myopia by enhancing intraocular inflammation.


Assuntos
Miopia , Fator de Crescimento Transformador beta , Humanos , Fator de Crescimento Transformador beta/metabolismo , NF-kappa B/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Retina , Miopia/genética , Miopia/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
3.
Transl Vis Sci Technol ; 13(1): 3, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38180775

RESUMO

Purpose: To compare baseline levels of exploratory biomarkers in the vitreous fluid of patients with primary retinal detachment who subsequently develop proliferative vitreoretinopathy (PVR) versus those who do not. Methods: In this exploratory case-control study, we evaluated the baseline protein biomarker levels from a biobank containing the vitreous fluid of patients who had undergone primary pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment. Undiluted samples were collected at the time of PPV and stored at -80°C. Samples from 13 patients who developed PVR within 6 months (PVR group) and 13 age- and gender-matched controls who did not develop PVR (control group) were included. Protein abundance levels were evaluated using a proximity extension assay, and a confirmatory enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of vimentin. Results: Baseline vimentin (Normalized Protein eXpression [NPX], 8.6 vs. 6.4, P < 0.0001) and heme oxygenase 1 (NPX 8.9 vs. 7.0, P < 0.001) levels were found to be elevated in vitreous fluid of patients who subsequently developed PVR compared to those who did not. Confirmatory analysis using ELISA demonstrated mean vimentin concentrations of 7254 vs. 2727 ng/mL in the PVR versus control groups (P = 0.0152). The odds ratio for developing PVR was 14 (confidence interval, 1.4-168; P = 0.03), assuming a baseline vimentin threshold of 7500 ng/mL. Conclusions: Vimentin is an intermediate filament protein expressed by retinal glial cells, and our data combined with prior evidence suggest that it may serve as an early vitreous biomarker for subsequent PVR formation and reactive gliosis. Furthermore, we found, for the first time, elevated baseline levels of heme oxygenase 1, a measurable indicator of oxidative stress. Translational Relevance: Our positive findings could impact clinical care for retinal detachment patients by facilitating risk stratification for targeted interventions or closer monitoring in those at the highest risk of developing PVR.


Assuntos
Descolamento Retiniano , Vitreorretinopatia Proliferativa , Humanos , Vitreorretinopatia Proliferativa/diagnóstico , Vitreorretinopatia Proliferativa/cirurgia , Vimentina , Heme Oxigenase-1 , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/cirurgia , Estudos de Casos e Controles , Biomarcadores
4.
PLoS One ; 19(1): e0296169, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38181006

RESUMO

BACKGROUND: The effects of anesthesia in patients undergoing thyroid cancer surgery are still not known. We investigated the relationship between the type of anesthesia and patient outcomes following elective thyroid cancer surgery. METHODS: This was a retrospective cohort study of patients who underwent elective surgical resection for papillary thyroid carcinoma between January 2009 and December 2019. Patients were grouped according to the type of anesthesia they received, desflurane or propofol. A Kaplan-Meier analysis was conducted, and survival/recurrence curves were presented from the date of surgery to death/recurrence. Univariable and multivariable Cox regression models were used to compare hazard ratios for recurrence after propensity matching. RESULTS: A total of 621 patients (22 deaths, 3.5%) under desflurane anesthesia and 588 patients (32 deaths, 5.4%) under propofol anesthesia were included. Five hundred and eighty-eight patients remained in each group after propensity matching. Propofol anesthesia was not associated with better survival compared to desflurane anesthesia in the matched analysis (P = 0.086). However, propofol anesthesia was associated with less recurrence (hazard ratio, 0.38; 95% confidence interval, 0.25-0.56; P < 0.001) in the matched analysis. CONCLUSIONS: Propofol anesthesia was associated with less recurrence, but not mortality, following surgery for papillary thyroid carcinoma than desflurane anesthesia. Further prospective investigation is needed to examine the influence of propofol anesthesia on patient outcomes following thyroid cancer surgery.


Assuntos
Propofol , Neoplasias da Glândula Tireoide , Humanos , Desflurano , Anestesia Intravenosa , Estudos Retrospectivos , Câncer Papilífero da Tireoide/cirurgia , Anestesia Geral , Neoplasias da Glândula Tireoide/cirurgia
5.
J Med Ethics ; 50(2): 97-101, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-37973369

RESUMO

Chat Generative Pre-Trained Transformer (ChatGPT) has been a growing point of interest in medical education yet has not been assessed in the field of bioethics. This study evaluated the accuracy of ChatGPT-3.5 (April 2023 version) in answering text-based, multiple choice bioethics questions at the level of US third-year and fourth-year medical students. A total of 114 bioethical questions were identified from the widely utilised question banks UWorld and AMBOSS. Accuracy, bioethical categories, difficulty levels, specialty data, error analysis and character count were analysed. We found that ChatGPT had an accuracy of 59.6%, with greater accuracy in topics surrounding death and patient-physician relationships and performed poorly on questions pertaining to informed consent. Of all the specialties, it performed best in paediatrics. Yet, certain specialties and bioethical categories were under-represented. Among the errors made, it tended towards content errors and application errors. There were no significant associations between character count and accuracy. Nevertheless, this investigation contributes to the ongoing dialogue on artificial intelligence's (AI) role in healthcare and medical education, advocating for further research to fully understand AI systems' capabilities and constraints in the nuanced field of medical bioethics.


Assuntos
Educação Médica , Medicina , Humanos , Criança , Inteligência Artificial , Princípios Morais , Idioma
6.
Semin Ophthalmol ; 39(2): 143-149, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37921332

RESUMO

OBJECTIVE: To report the incidence, risk factors and management of postoperative complications after horizontal strabismus surgery. DESIGN: Retrospective Cohort study. PARTICIPANTS: The study assessed 1,273 patients with 1,035 cases of exotropia and 238 cases of esotropia, with a minimum 18-month follow-up. METHODS: Retrospective review of strabismus operation patients' medical records included baseline demographics, age at surgery, pre/postoperative visual acuity, and deviation. Complications were categorized as surgical site (infection, scarring, cyst, granuloma, ischemia) and strabismus-related (recurrence, diplopia), with analysis of incidence, risk factors, and management. RESULTS: Among surgical site complications, the incidence of infection, pyogenic granuloma, and anterior segment ischemia were similar between the exotropia (0.3%, 0.3%, 0.2%) and esotropia (0.8%, 0%, 0.4%) groups (p = .221, 0.406, 0.515). In contrast, the esotropia group presented a higher risk of conjunctival inclusion cyst and conjunctival scar than the exotropia group, with incidences of 5.0% vs 2.2% and 6.3% vs 1.3%, respectively (p = .004, <0.001). Regarding strabismus complications, the incidence of early recurrence was not significant between the two groups, with 10.0% in the exotropia group and 10.5% in the esotropia group (p = .553). Older age and poor initial visual acuity were associated with early recurrence (p < .001). The esotropia group had a higher risk of persistent diplopia than the exotropia group, with incidences of 4.2% vs 2.0%, respectively (p = .003). CONCLUSION: Esotropia carries a higher risk of conjunctival inclusion cysts, conjunctival scarring, and persistent diplopia compared to the exotropia group, while both groups exhibit similar rates of early recurrence and other surgical site complications.


Assuntos
Cistos , Esotropia , Exotropia , Estrabismo , Humanos , Esotropia/cirurgia , Incidência , Diplopia , Estudos Retrospectivos , Cicatriz/complicações , Cicatriz/cirurgia , Procedimentos Cirúrgicos Oftalmológicos/efeitos adversos , Estrabismo/epidemiologia , Estrabismo/cirurgia , Estrabismo/complicações , Músculos Oculomotores/cirurgia , Fatores de Risco , Transtornos da Visão , Infecção da Ferida Cirúrgica , Cistos/complicações , Cistos/cirurgia , Isquemia/complicações , Isquemia/cirurgia , Seguimentos , Complicações Pós-Operatórias/cirurgia
9.
Mol Ecol ; 32(18): 5071-5088, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37584177

RESUMO

Acquisition of new genes often results in the emergence of novel functions and is a key step in lineage-specific adaptation. As a group of sessile crustaceans, barnacles establish permanent attachment through initial cement secretion at the larval phase followed by continuous cement secretion in juveniles and adults. However, the origins and evolution of barnacle larval and adult cement proteins remain poorly understood. By performing microdissection of larval cement glands, transcriptome and shotgun proteomics and immunohistochemistry validation, we identified 30 larval and 27 adult cement proteins of the epibiotic turtle barnacle Chelonibia testudinaria, of which the majority are stage- and barnacle-specific. While only two proteins, SIPC and CP100K, were expressed in both larvae and adults, detection of protease inhibitors and the cross-linking enzyme lysyl oxidase paralogs in larvae and adult cement. Other barnacle-specific cement proteins such as CP100k and CP52k likely share a common origin dating back at least to the divergence of Rhizocephala and Thoracica. Different CP52k paralogues could be detected in larval and adult cement, suggesting stage-specific cement proteins may arise from duplication followed by changes in expression timing of the duplicates. Interestingly, the biochemical properties of larval- and adult-specific CP52k paralogues exhibited remarkable differences. We conclude that barnacle larval and adult cement systems evolved independently, and both emerged from co-option of existing genes and de novo formation, duplication and functional divergence of lineage-specific cement protein genes. Our findings provide important insights into the evolutionary mechanisms of bioadhesives in sessile marine invertebrates.


Assuntos
Thoracica , Animais , Thoracica/genética , Thoracica/metabolismo , Proteínas/genética , Larva/genética , Larva/metabolismo , Transcriptoma/genética
10.
Graefes Arch Clin Exp Ophthalmol ; 261(12): 3457-3464, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37581651

RESUMO

PURPOSE: To investigate whether patients with central serous chorioretinopathy (CSC) have increased risk of developing glaucoma. METHODS: Patients diagnosed with CSC between 1 January 2008 and 31 December 2018 were included in this study using data from the Taiwanese National Health Insurance Research Database (NHIRD). The CSC cohort was matched with a non-CSC cohort using the propensity score matching method, based on sex, age (in 10-year intervals), index date year, comorbidities, and steroid use, resulting in equal numbers of patients in both cohorts. Patients were followed up until 31 December 2019 or until they were withdrawn from the NHIRD. The incidence of glaucoma was compared between the two cohorts using the Cox regression model, and the risk of developing glaucoma was estimated using the Kaplan-Meier method. RESULTS: After adjusting for sex, age, comorbidities, and steroid use, the CSC cohort showed a significantly higher risk of developing glaucoma compared to those without CSC (adjusted HR = 3.99; 95% CI = 3.44-4.62). The cumulative incidence of glaucoma in the CSC cohort was also significantly higher than in the non-CSC cohort (log-rank test, p < 0.001). Among the glaucoma subtypes, normal tension glaucoma had the highest risk (adjusted HR = 5.79; 95% CI = 3.41-9.85), followed by primary open-angle glaucoma (adjusted HR = 2.77; 95% CI = 2.12-3.62). CONCLUSIONS: In conclusion, our study shows that CSC patients are at a higher risk of developing glaucoma, especially NTG. Awareness and regular glaucoma screenings are essential for patients with CSC.


Assuntos
Coriorretinopatia Serosa Central , Glaucoma de Ângulo Aberto , Glaucoma , Humanos , Estudos de Coortes , Coriorretinopatia Serosa Central/complicações , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/epidemiologia , Glaucoma/diagnóstico , Glaucoma/epidemiologia , Esteroides , Fatores de Risco , Estudos Retrospectivos
11.
Acupunct Med ; 41(6): 364-375, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37211683

RESUMO

BACKGROUND: Dopamine has been suggested to be a stop signal for eye growth and affects the development of myopia. Acupuncture is known to increase dopamine secretion and is widely used to treat myopia clinically. OBJECTIVE: The aim of this study was to determine if acupuncture inhibits myopia progression in form deprived Syrian hamsters by inducing rises in dopamine content that in turn suppress inflammasome activation. METHODS: Acupuncture was applied at LI4 and Taiyang every other day for 21 days. The levels of molecules associated with the dopamine signaling pathway, inflammatory signaling pathway and inflammasome activation were determined. A dopamine agonist (apomorphine) was used to evaluate if activation of the dopaminergic signaling pathway suppresses myopia progression by inhibiting inflammasome activation in primary retinal pigment epithelial (RPE) cells. A dopamine receptor 1 (D1R) inhibitor (SCH39166) was also administered to the hamsters. RESULTS: Acupuncture inhibited myopia development by increasing dopamine levels and activating the D1R signaling pathway. Furthermore, we also demonstrated that nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat (LRR)- and pyrin domain-containing protein 3 (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome activation was inhibited by activation of the D1R signaling pathway. CONCLUSION: Our findings suggest that acupuncture inhibits myopia development by suppressing inflammation, which is initiated by activation of the dopamine-D1R signaling pathway.


Assuntos
Terapia por Acupuntura , Miopia , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Dopamina , Transdução de Sinais , Miopia/genética , Miopia/terapia
12.
BMC Complement Med Ther ; 22(1): 271, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36242032

RESUMO

BACKGROUND: The increased global incidence of myopia requires the establishment of therapeutic approaches. This study aimed to investigate the effect of Fallopia Japonica (FJ) and Prunella vulgaris (PV) extract on myopia caused by monocular form deprivation (MFD). METHODS: We used human retinal pigment epithelial cell to study the molecular mechanisms on how FJ extract (FJE) and PV extract (PVE) lowering the inflammation of the eye. The effect of FJE and PVE in MFD induced hamster model and explore the role of inflammation cytokines in myopia. RESULTS: FJE + PVE reduced IL-6, IL-8, and TNF-α expression in RPE cells. Furthermore, FJE and PVE inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. In addition, we report two resveratrol + ursolic acid compounds from FJ and PV and their inhibitory activities against IL-6, IL-8, and TNF-α expression levels in RPE cells treated with IL-6 and TNF-α. FJE, PVE, and FJE + PVE were applied to MFD hamsters and their axial length was measured after 21 days. The axial length showed statistically significant differences between phosphate-buffered saline- and FJE-, PVE-, and FJE + PVE-treated MFD eyes. FJE + PVE suppressed expressions of IL-6, IL-8, and TNF-α. They also inhibited myopia-related transforming growth factor-beta (TGF)-ß1, matrix metalloproteinase (MMP)-2, and NF-κB expression while increasing type I collagen expression. CONCLUSIONS: Overall, these results suggest that FJE + PVE may have a therapeutic effect on myopia and be used as a potential treatment option.


Assuntos
Fallopia japonica , Miopia , Prunella , Animais , Colágeno Tipo I , Cricetinae , Fallopia japonica/metabolismo , Humanos , Inflamação , Interleucina-6/metabolismo , Interleucina-8 , Metaloproteinases da Matriz , Miopia/epidemiologia , Miopia/etiologia , NF-kappa B/metabolismo , Fosfatos , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt , Resveratrol , Pigmentos da Retina , Fatores de Crescimento Transformadores , Fator de Necrose Tumoral alfa/metabolismo
13.
Curr Opin Allergy Clin Immunol ; 22(5): 319-327, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36094134

RESUMO

PURPOSE OF REVIEW: As the conjunctiva is embryologically modified skin, ocular surface involvement can be observed in several atopic skin diseases. The purpose of this review is to highlight and compare the roles of type 2 cytokines in the skin and ocular surface, and their resulting disorders. RECENT FINDINGS: Although there have been extensive studies identifying various type 2 cytokine pathways in the skin, there is limited analyses of pathways assessed on the ocular surface. We provide the potential overlapping cytokine impacts on the skin and eye including interleukin (IL)-4, IL-5 IL-13, IL-25, IL-33, thymic stromal lymphopoietin (TSLP), and IL-31 that may provide important immunomodulatory interventions and treatment for the more chronic and sight-threatening ocular disorders. SUMMARY: Dysregulation of type 2 inflammatory cytokines was found to elicit similar immunopathogenic responses on the skin and ocular surfaces, leading to barrier dysfunction, remodeling, immune cell recruitment, and symptoms such as pruritus.


Assuntos
Citocinas , Pele , Citocinas/metabolismo , Olho/metabolismo , Humanos , Imunomodulação , Prurido
14.
Curr Issues Mol Biol ; 44(9): 4303-4313, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36135208

RESUMO

In this study, we aimed to investigate whether chronic retinal inflammation is involved in the pathogenesis of form-deprivation myopia (FDM) using tree shrews as an animal model. Twenty-one tree shrews were randomly divided into 7-day/14-day FDM (FDM7/FDM14) groups and their corresponding 7-day/14-day control groups. Refraction and axial length were measured. To determine the effects of form deprivation on inflammation, we used real-time polymerase chain reaction (PCR) and immunohistochemistry to assess the expression levels of several proinflammatory cytokines. At day 0, the eyes in the FDM and control groups were hyperopic. However, after 7 and 14 days of form deprivation, the refractive error of the eyes in the FDM7 and FDM14 groups shifted from +6.6 ± 0.3 diopters (D) to +4.0 ± 0.5 D and from +6.4 ± 0.3 D to +5.0 ± 0.3 D, respectively. The levels of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, and nuclear factor κB were increased in the FDM eyes, compared with those in the control eyes. The increase in matrix metalloproteinase-2 expression was greater in the FDM eyes than in the contralateral and control eyes, whereas collagen type I expression was downregulated. In conclusion, chronic inflammation may play a crucial pathogenic role in form-deprivation myopia in tree shrews.

15.
Health Serv Insights ; 15: 11786329221114759, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36034733

RESUMO

Objective: The concussion team at The University of Kansas Health System outpatient rehabilitation spine center is comprised of experienced multi-disciplinary experts including physical therapists and a speech language pathologist. The team set forth with a purpose of creating and organizing an internal physical therapy clinical recommendation protocol for initial evaluations and subsequent treatments for the concussed patient. The aim of this paper is to share these recommendation protocols with other therapy teams and provide a foundational layout for treating the patient with post-concussion symptoms in an outpatient physical therapy clinical setting. Study design: Clinical recommendation protocol provides guidance for patients ages 10+ from initial evaluation through discharge with emphasis on evidence-based research in the areas of: oculomotor, cervical, vestibular, post-concussion migraine influence, mood disorders(such as anxiety and depression), exertion, and cognitive communicative dysfunction. Results: Finding a written, comprehensive clinical resource protocol for post-concussion outpatient evaluation(s) and treatment strategies can be difficult. This document serves as a resource for other outpatient concussion rehabilitation clinics, providing rationale, and objective measurement tools, for assessing and treating concussion patients. To the authors' knowledge, no other research has produced a practical, efficient evaluation tool to be utilized at bed side, condensing evidence-based research into an easy-to-use form. Conclusion: The University of Kansas Health System outpatient concussion rehabilitation center developed clinical recommendation protocols for concussion care. The intent was to standardize assessment and treatment for concussion patients and to share these objective measurement tools and procedures, focused on a team approach of concussion providers, as a clinical outline for both the novice and seasoned clinician specializing in the field of concussion work in an outpatient rehabilitation setting.

17.
Lancet Infect Dis ; 22(5): 611-621, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35286843

RESUMO

BACKGROUND: Non-antiviral therapeutic options are required for the treatment of hospitalised patients with COVID-19. CD24Fc is an immunomodulator with potential to reduce the exaggerated inflammatory response to tissue injuries. We aimed to evaluate the safety and efficacy of CD24Fc in hospitalised adults with COVID-19 receiving oxygen support. METHODS: We conducted a randomised, double-blind, placebo-controlled, phase 3 study at nine medical centres in the USA. Hospitalised patients (age ≥18 years) with confirmed SARS-CoV-2 infection who were receiving oxygen support and standard of care were randomly assigned (1:1) by site-stratified block randomisation to receive a single intravenous infusion of CD24Fc 480 mg or placebo. The study funder, investigators, and patients were masked to treatment group assignment. The primary endpoint was time to clinical improvement over 28 days, defined as time that elapsed between a baseline National Institute of Allergy and Infectious Diseases ordinal scale score of 2-4 and reaching a score of 5 or higher or hospital discharge. The prespecified primary interim analysis was done when 146 participants reached the time to clinical improvement endpoint. Efficacy was assessed in the intention-to-treat population. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT04317040. FINDINGS: Between April 24 and Sept 22, 2020, 243 hospitalised patients were assessed for eligibility and 234 were enrolled and randomly assigned to receive CD24Fc (n=116) or placebo (n=118). The prespecified interim analysis was done when 146 participants reached the time to clinical improvement endpoint among 197 randomised participants. In the interim analysis, the 28-day clinical improvement rate was 82% (81 of 99) for CD24Fc versus 66% (65 of 98) for placebo; median time to clinical improvement was 6·0 days (95% CI 5·0-8·0) in the CD24Fc group versus 10·0 days (7·0-15·0) in the placebo group (hazard ratio [HR] 1·61, 95% CI 1·16-2·23; log-rank p=0·0028, which crossed the prespecified efficacy boundary [α=0·0147]). 37 participants were randomly assigned after the interim analysis data cutoff date; among the 234 randomised participants, median time to clinical improvement was 6·0 days (95% CI 5·0-9·0) in the CD24Fc group versus 10·5 days (7·0-15·0) in the placebo group (HR 1·40, 95% CI 1·02-1·92; log-rank p=0·037). The proportion of participants with disease progression within 28 days was 19% (22 of 116) in the CD24Fc group versus 31% (36 of 118) in the placebo group (HR 0·56, 95% CI 0·33-0·95; unadjusted p=0·031). The incidences of adverse events and serious adverse events were similar in both groups. No treatment-related adverse events were observed. INTERPRETATION: CD24Fc is generally well tolerated and accelerates clinical improvement of hospitalised patients with COVID-19 who are receiving oxygen support. These data suggest that targeting inflammation in response to tissue injuries might provide a therapeutic option for patients hospitalised with COVID-19. FUNDING: Merck & Co, National Cancer Institute, OncoImmune.


Assuntos
Tratamento Farmacológico da COVID-19 , Adolescente , Adulto , Método Duplo-Cego , Humanos , Fatores Imunológicos/efeitos adversos , Oxigênio , SARS-CoV-2 , Resultado do Tratamento
18.
BMC Ophthalmol ; 21(1): 426, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34886822

RESUMO

BACKGROUND: This study aimed to investigate the risk of Parkinson's disease (PD) among patients with age-related macular degeneration (AMD) and its association with confounding comorbidities. METHODS: A population-based retrospective cohort study was conducted using Longitudinal Health Insurance Database 2000 (LHID2000). We established AMD and non-AMD cohorts from January 1, 2000 to December 31, 2012 to determine the diagnosis of PD. A total of 20,848 patients were enrolled, with 10,424 AMD patients and 10,424 controls matched for age, sex, and index year at a 1:1 ratio. The follow-up period was from the index date of AMD diagnosis to the diagnosis of PD, death, withdrawal from the insurance program, or end of 2013. Multivariable Cox regression analysis was performed to examine the hazard ratio (HR) and 95% confidence interval (CI) for the risk of PD between the AMD and non-AMD cohorts. RESULT: After adjusting for potential confounders, there was a higher risk of developing PD in the AMD cohort than in the non-AMD cohort (adjusted HR = 1.35, 95% CI = 1.16-1.58). A significant association could be observed in both female (aHR = 1.42, 95% CI = 1.13-1.80) and male (aHR = 1.28, 95% CI = 1.05-1.57) patients, aged more than 60 years (60-69: aHR = 1.51, 95% CI = 1.09-2.09, 70-79: aHR = 1.30, 95% CI = 1.05-1.60; 80-100: aHR = 1.40, 95% CI = 1.01-1.95), and with more than one comorbidity (aHR = 1.40, 95% CI = 1.20-1.64). A significant association between increased risk of PD and AMD was observed among patients with comorbidities of osteoporosis (aHR = 1.68, 95% CI = 1.22-2.33), diabetes (aHR = 1.41, 95% CI = 1.12-1.78) and hypertension (aHR = 1.36, 95% CI = 1.15-1.62) and medications of statin (aHR = 1.42, 95% CI = 1.19-1.69) and calcium channel blocker (CCB) (aHR = 1.32, 95% CI = 1.11-1.58). The cumulative incidence of PD was significantly higher over the 12-year follow-up period in AMD cohort (log-rank test, p < 0.001). CONCLUSIONS: Patients with AMD may exhibit a higher risk of PD than those without AMD.


Assuntos
Degeneração Macular , Doença de Parkinson , Estudos de Coortes , Feminino , Humanos , Incidência , Degeneração Macular/epidemiologia , Degeneração Macular/etiologia , Masculino , Doença de Parkinson/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taiwan
19.
J Clin Med ; 10(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34640450

RESUMO

BACKGROUND: The aim was to investigate the effect of inferior oblique (IO) operation (IO myectomy or graded recession and anteriorization) for unilateral and bilateral superior oblique muscle palsy (SOP); Methods: A total of 167 eyes undergoing IO surgery by a single surgeon between 2008 and 2015 were retrospectively reviewed. The method for treating symmetric bilateral SOP was bilateral IO myectomy (n = 102) and the method for treating unilateral SOP or non-symmetric bilateral SOP was IO-graded recession and anteriorization (n = 65). Associated clinical results and other factors were analyzed; Results: Head tilt, vertical deviation, IO overaction, SO underaction degree and ocular torsion angle were all clearly changed, but there was no statistically significance between these two procedures. Mean preoperative torsional angle was 15.3 ± 6.4 degree, which decreased to 5.3 ± 2.7 degree after surgery. Preoperative torsional angle, IOOA and SOUA degree were all significantly affected in postoperative torsional angle (p = 0.025, 0.003 and 0.038). Horizontal rectus muscle and IO muscle operation did not interfere with each other's results (p = 0.98); Conclusions: Symmetric bilateral SOP could be treated with bilateral IO myectomy and IO-graded recession and anteriorization should be reserved for unilateral SOP or non-symmetric bilateral SOP.

20.
Mediators Inflamm ; 2021: 6660640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285659

RESUMO

Myopia is a highly prevalent refractive disorder. We investigated the effect of diacerein on monocular form deprivation (MFD) in hamsters as a possible therapeutic intervention. Diacerein is an anthraquinone derivative drug whose active metabolite is rhein. Diacerein or atropine was applied to the MFD hamsters, and their refractive error and axial length were measured after 21 days. The refractive error (control: -0.91 ± 0.023, atropine: -0.3 ± 0.08, and diacerein: -0.27 ± 0.07 D) and axial length (control: 0.401 ± 0.017, atropine: 0.326 ± 0.017, and diacerein: 0.334 ± 0.016 mm) showed statistically significant differences between control, atropine-treated, and diacerein-treated MFD eyes. Furthermore, we determined the level of transforming growth factor-beta- (TGF-) ß1, matrix metalloproteinase- (MMP-) 2, type I collagen, interleukin- (IL-) 6, IL-8, and monocyte chemoattractant protein- (MCP-) 1 in the retina. Atropine and diacerein suppressed levels of the myopia-related TGF-ß1 and MMP-2 while increasing type I collagen expression. They also inhibited the interleukin IL-6, IL-8, and MCP-1 levels. Diacerein reduced the IL-6, IL-8, and MCP-1 expression in ARPE-19 cells. Furthermore, diacerein inhibited inflammation by attenuating the phosphorylation of protein kinase B (AKT) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) pathway. This suggests that diacerein has a therapeutic effect on myopia and is a potential treatment option.


Assuntos
Inflamação , Miopia , Animais , Antraquinonas/uso terapêutico , Cricetinae , Células Epiteliais/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Miopia/tratamento farmacológico , Miopia/metabolismo , Pigmentos da Retina/metabolismo
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