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1.
Korean J Intern Med ; 39(5): 855-864, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39252490

RESUMO

BACKGROUND/AIMS: To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHODS: This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation. RESULTS: The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable. CONCLUSION: Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.


Assuntos
Abatacepte , Antirreumáticos , Artrite Reumatoide , Doenças Pulmonares Intersticiais , Humanos , Abatacepte/uso terapêutico , Abatacepte/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/complicações , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/diagnóstico , Antirreumáticos/uso terapêutico , Antirreumáticos/efeitos adversos , Idoso , Resultado do Tratamento , Progressão da Doença , Fatores de Tempo , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Fatores de Risco , Adulto , República da Coreia , Tomografia Computadorizada por Raios X
3.
J Clin Med ; 13(16)2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39201079

RESUMO

Background: While numerous studies have been conducted on sudden sensorineural hearing loss (SSNHL), research on how treatment outcomes and prognosis vary by age remains insufficient. This study aims to investigate the differences in recovery rates among SSNHL patients divided by age groups. Methods: A retrospective study was conducted on 177 patients diagnosed with SSNHL from 2020 to 2023. The patients were categorized into four age groups: under 20, 30-40, 50-60, and over 70. Recovery rates and associated symptoms were compared across these groups. Results: Significant recovery rates were observed in all age groups except for those over 70 (p = 0.006, p = 0.003, p = 0.009). No significant differences were found in recovery rates based on gender (p > 0.75) or symptoms such as tinnitus, ear fullness, and dizziness (p > 0.05). Conclusions: The study revealed that younger and middle-aged adults showed statistically significant improvements in recovery rates, while the elderly exhibited relatively lower recovery rates.

4.
Mol Genet Genomics ; 299(1): 78, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39120737

RESUMO

Height is known to be a classically heritable trait controlled by complex polygenic factors. Numerous height-associated genetic variants across the genome have been identified so far. It is also a representative of externally visible characteristics (EVC) for predicting appearance in forensic science. When biological evidence at a crime scene is deficient in identifying an individual, the examination of forensic DNA phenotyping using some genetic variants could be considered. In this study, we aimed to predict 'height', a representative forensic phenotype, by using a small number of genetic variants when short tandem repeat (STR) analysis is hard with insufficient biological samples. Our results not only replicated previous genetic signals but also indicated an upward trend in polygenic score (PGS) with increasing height in the validation and replication stages for both genders. These results demonstrate that the established SNP sets in this study could be used for height estimation in the Korean population. Specifically, since the PGS model constructed in this study targets only a small number of SNPs, it contributes to enabling forensic DNA phenotyping even at crime scenes with a minimal amount of biological evidence. To the best of our knowledge, this was the first study to evaluate a PGS model for height estimation in the Korean population using GWAS signals. Our study offers insight into the polygenic effect of height in East Asians, incorporating genetic variants from non-Asian populations.


Assuntos
Povo Asiático , Estatura , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Humanos , Masculino , Herança Multifatorial/genética , Feminino , Estatura/genética , República da Coreia , Povo Asiático/genética , Genética Forense/métodos , Adulto , Estudo de Associação Genômica Ampla/métodos , Fenótipo , Repetições de Microssatélites/genética , Pessoa de Meia-Idade
5.
Antiviral Res ; 230: 105979, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39111639

RESUMO

Orally dissolving films (ODF) are designed to be dissolved on the tongue and absorbed in the mouth. It offers multiple advantages over the commonly used needle-based vaccines, especially in terms of convenience allowing safe, painless, and easy self-administration. As the efficacy of ODF-encapsulated influenza vaccines has not been demonstrated, we assessed the protection elicited by inactivated influenza virus (A/PR/8/34, H1N1) vaccine delivered using ODFs in mice. Trehalose and pullulan components of the ODF ensured that the HA antigens of the inactivated PR8 virus retained their stability while ensuring the rapid release of the vaccines upon exposure to murine saliva. Mice were immunized thrice by placing the PR8-ODF on the tongues of mice at 4-week intervals, and vaccine-induced protection was evaluated upon lethal homologous challenge infection. The PR8-ODF vaccination elicited virus-specific serum IgG and IgA antibody responses, hemagglutinin inhibition (HAI), and viral neutralization. Upon challenge infection, ODF vaccination showed higher levels of IgG and IgA antibody responses in the lungs and antibody-secreting cell (ASC) responses in both lung and spleen compared to unimmunized controls. These results corresponded with the enhanced T cell and germinal center B cell responses in the lungs and spleens. Importantly, ODF vaccination significantly reduced lung virus titers and inflammatory cytokines (IFN-γ, IL-6) production compared to unvaccinated control. ODF vaccination ensured 100% survival and prevented weight loss in mice. These findings suggest that influenza vaccine delivery through ODFs could be a promising approach for oral vaccine development.


Assuntos
Anticorpos Antivirais , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Vacinas de Produtos Inativados , Animais , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Camundongos , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Anticorpos Antivirais/sangue , Administração Oral , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Feminino , Camundongos Endogâmicos BALB C , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Pulmão/virologia , Pulmão/imunologia , Vacinação/métodos , Portadores de Fármacos
6.
Mol Cell Proteomics ; 23(9): 100824, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39097268

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) suffers from a lack of an effective diagnostic method, which hampers improvement in patient survival. Carbohydrate antigen 19-9 (CA19-9) is the only FDA-approved blood biomarker for PDAC, yet its clinical utility is limited due to suboptimal performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics for the discovery, verification, and validation of novel biomarkers. A plethora of protein biomarker candidates for PDAC have been identified using LC-MS, yet few has successfully transitioned into clinical practice. This translational standstill is owed partly to insufficient considerations of practical needs and perspectives of clinical implementation during biomarker development pipelines, such as demonstrating the analytical robustness of proposed biomarkers which is critical for transitioning from research-grade to clinical-grade assays. Moreover, the throughput and cost-effectiveness of proposed assays ought to be considered concomitantly from the early phases of the biomarker pipelines for enhancing widespread adoption in clinical settings. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS protocol. In the discovery phase, we comprehensively surveyed putative PDAC biomarkers from both in-house data and prior studies. In the verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation tests. We adopted a high-throughput protocol including a short gradient (<10 min) and simple sample preparation (no depletion or enrichment steps). Additionally, we developed our assay using serum samples, which are usually the preferred biospecimen in clinical settings. We developed predictive models based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone in discriminating PDAC from non-PDAC controls including healthy individuals and patients with benign pancreatic diseases. A large-scale clinical validation is underway to demonstrate the clinical validity of our novel panel.

7.
Korean J Ophthalmol ; 38(4): 304-315, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39013560

RESUMO

PURPOSE: This study aimed to determine the incidence and visual outcomes of pachychoroid neovasculopathy (PNV) in patients initially diagnosed with central serous chorioretinopathy (CSC). METHODS: In this study, 144 patients aged 20 to 55 years with treatment-naive chronic CSC, defined as the persistence of subretinal fluid (SRF) for ≥6 months, were retrospectively enrolled. Patients with PNV at the initial evaluation were categorized as group 1, whereas those who developed new-onset PNV during follow-up were categorized as group 2. Patients without PNV until the end of the follow-up were categorized as group 3. RESULTS: Over a mean follow-up period of 49.9 ± 39.9 months, new-onset PNV was diagnosed in 11.8% of patients with CSC. The time taken to reach the initial resolution was longest in group 1 (group 1, 11.13 ± 10.70 months; group 2, 8.14 ± 7.90 months; group 3, 7.32 ± 9.55 months), although these differences were not statistically significant. The numbers of injections needed to achieve initial resolution were 3.76 ± 5.90, 1.64 ± 2.06, and 1.74 ± 4.33 in groups 1, 2, and 3, respectively, with no significant differences. SRF recurrence was recorded in seven patients (29.2%) in group 1, nine (64.3%) in group 2, and 28 (26.7%) in group 3. The recurrence rates were significantly higher in group 2 than those in group 1 or 3. At the end of the follow-up period, significant improvements in best-corrected visual acuity were achieved in groups 1 and 3, compared with baseline, but not in group 2. CONCLUSIONS: Patients with chronic CSC with new-onset PNV exhibited higher SRF recurrence and worse visual outcomes compared to those with initial PNV or those with chronic CSC without PNV. Our study emphasizes the importance of routine screening for prompt diagnoses of new-onset PNV in individuals with chronic CSC.


Assuntos
Coriorretinopatia Serosa Central , Angiofluoresceinografia , Fundo de Olho , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Coriorretinopatia Serosa Central/diagnóstico , Coriorretinopatia Serosa Central/complicações , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , Seguimentos , Adulto Jovem , Neovascularização de Coroide/diagnóstico , Incidência , Líquido Sub-Retiniano , Corioide/irrigação sanguínea , Corioide/patologia
8.
Animals (Basel) ; 14(14)2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39061596

RESUMO

Ensuring the safety of mesenchymal stem cell (MSC) therapy is a fundamental requirement in clinical practice. This study aimed to assess the safety of using gonadal tissue-derived MSCs (n = 10) compared to the commonly utilized adipose tissue-derived MSCs (n = 9) in geriatric dogs with chronic diseases. All participants received allogeneic MSC therapy, and no allergic reactions due to allogeneic cell immunogenicity were noted. Both groups showed no adverse changes in physical exams or hematological parameters before and after therapy. Importantly, there were no instances of tumor formation or growth post-treatment in either group. The findings demonstrated that dogs treated with gonadal tissue-derived MSCs experienced no clinical adverse effects. However, clinical adverse effects were reported in one case of adipose tissue-derived MSC therapy. Despite limitations in monitoring beyond one year and constraints due to a small and diverse patient group, this pioneering study validates the safe use of gonadal tissue-derived MSCs in aged companion animals. It underscores the potential of utilizing tissues from neutering procedures to advance regenerative medicine and expand cell banks and therapy options for companion animals.

9.
Retina ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39028983

RESUMO

PURPOSE: This retrospective case series aimed to assess the concordance between clinical diagnoses of punctate inner choroidopathy (PIC) and multifocal choroiditis and panuveitis (MCP) using the 2021 Standardization of Uveitis Nomenclature (SUN) Working Group criteria. METHODS: Using the medical records of the patients, we reevaluated 100 eyes of 75 patients with idiopathic multifocal chorioretinal inflammatory lesions based on SUN criteria and compared the result to the clinical diagnosis. RESULTS: Of 100 eyes, 29 eyes (29%) were diagnosed as PIC and 15 eyes (15%) were diagnosed as MCP using SUN criteria, and 56 (56%) eyes could not be diagnosed as either. Clinically diagnosed PIC eyes were significantly more myopic than the clinically diagnosed MCP eyes (mean spherical equivalent -6.65 ± 4.63 vs. -3.85 ± 2.31, P = 0.01). Sixteen eyes with vitreous inflammation were all clinically diagnosed as MCP, but four (25%) could not be diagnosed as MCP using SUN criteria. CONCLUSIONS: The existing diagnostic criteria showed limitations in capturing all clinical cases of PIC or MCP, and adding or revising criteria on features such as vitreous inflammation or myopia, could be considered to enhance diagnostic accuracy.

10.
Curr Issues Mol Biol ; 46(7): 7769-7781, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39057101

RESUMO

Although several methods are being applied to treat peripheral nerve injury, a perfect treatment that leads to full functional recovery has not yet been developed. SMAD (Suppressor of Mothers Against Decapentaplegic Homolog) plays a crucial role in nerve regeneration by facilitating the survival and growth of nerve cells following peripheral nerve injury. We conducted a systematic literature review on the role of SMAD in this context. Following peripheral nerve injury, there was an increase in the expression of SMAD1, -2, -4, -5, and -8, while SMAD5, -6, and -7 showed no significant changes; SMAD8 expression was decreased. Specifically, SMAD1 and SMAD4 were found to promote nerve regeneration, whereas SMAD2 and SMAD6 inhibited it. SMAD exerts its effects by promoting neuronal survival and growth through BMP/SMAD1, BMP/SMAD4, and BMP/SMAD7 signaling pathways. Furthermore, it activates nerve regeneration programs via the PI3K/GSK3/SMAD1 pathway, facilitating active regeneration of nerve cells and subsequent functional recovery after peripheral nerve damage. By leveraging these mechanisms of SMAD, novel strategies for treating peripheral nerve damage could potentially be developed. We aim to further elucidate the precise mechanisms of nerve regeneration mediated by SMAD and explore the potential for developing targeted nerve treatments based on these findings.

11.
Clin Pract ; 14(4): 1383-1390, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39051305

RESUMO

BACKGROUND: No studies to date have compared audiologic characteristics in patients with continuous and intermittent tinnitus. The present study classified tinnitus patients into continuous and intermittent groups based on tinnitus duration and compared their audiologic characteristics. METHODS: This study enrolled 604 patients with tinnitus from January 2019 to December 2022. Clinical manifestations, PTA results, the frequency and loudness of tinnitus, ABR, DPOAE, and TEOAE tests were compared in patients with continuous and intermittent tinnitus. RESULTS: Of the 604 patients, 231 (38.2%) had continuous and 373 (61.8%) had intermittent tinnitus. There were no significant between-group differences in otologic symptoms, tinnitus onomatopoeia. PTA showed that hearing thresholds, except at 125 Hz, were significantly higher in patients with continuous rather than intermittent tinnitus. The loudness of tinnitus was significantly greater in patients with continuous rather than intermittent tinnitus. ABR tests showed that the absolute latency of wave V was significantly longer in continuous than in intermittent tinnitus. Signal-to-noise ratios on TEOAE tests were significantly lower in patients with continuous rather than intermittent tinnitus at all frequencies tested (1, 1.5, 2, 3, and 4 kHz). Response rates to sound stimuli at all frequencies, except for 1 kHz, were significantly lower on DPOAE tests in patients with continuous rather than intermittent tinnitus. CONCLUSIONS: Continuous tinnitus is more common in males, more persistent over time, and is associated with a higher rate of hearing loss. In contrast, intermittent tinnitus is more common in women, appears acutely, and is associated with a relatively lower rate of hearing loss. Based on the findings of the current paper, it seems that audiologic characteristics may differ between patients with continuous and intermittent tinnitus.

12.
Int J Mol Sci ; 25(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-39000011

RESUMO

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and affects millions of individuals globally. AD is associated with cognitive decline and memory loss that worsens with aging. A statistical report using U.S. data on AD estimates that approximately 6.9 million individuals suffer from AD, a number projected to surge to 13.8 million by 2060. Thus, there is a critical imperative to pinpoint and address AD and its hallmark tau protein aggregation early to prevent and manage its debilitating effects. Amyloid-ß and tau proteins are primarily associated with the formation of plaques and neurofibril tangles in the brain. Current research efforts focus on degrading amyloid-ß and tau or inhibiting their synthesis, particularly targeting APP processing and tau hyperphosphorylation, aiming to develop effective clinical interventions. However, navigating this intricate landscape requires ongoing studies and clinical trials to develop treatments that truly make a difference. Genome-wide association studies (GWASs) across various cohorts identified 40 loci and over 300 genes associated with AD. Despite this wealth of genetic data, much remains to be understood about the functions of these genes and their role in the disease process, prompting continued investigation. By delving deeper into these genetic associations, novel targets such as kinases, proteases, cytokines, and degradation pathways, offer new directions for drug discovery and therapeutic intervention in AD. This review delves into the intricate biological pathways disrupted in AD and identifies how genetic variations within these pathways could serve as potential targets for drug discovery and treatment strategies. Through a comprehensive understanding of the molecular underpinnings of AD, researchers aim to pave the way for more effective therapies that can alleviate the burden of this devastating disease.


Assuntos
Doença de Alzheimer , Proteínas tau , Doença de Alzheimer/metabolismo , Doença de Alzheimer/etiologia , Humanos , Proteínas tau/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Estudo de Associação Genômica Ampla , Proteólise
13.
Rev Cardiovasc Med ; 25(4): 118, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39076559

RESUMO

Pacing induced cardiomyopathy (PICM) can occur as a complication due to pacing the right ventricle. Its precise definition varies across different studies, leading to uncertainty as to the best approach for managing this entity. More than 10% of patients who undergo chronic right ventricular pacing develop PICM. Risk factors associated with PICM include reduced left ventricular ejection fraction (LVEF), the proportion of right ventricular pacing, and paced QRS duration. The main approach to treating PICM has been upgrading to biventricular pacing cardiac resynchronization therapy when the LVEF decreases. However, emerging evidence suggest that conduction system pacing might provide an opportunity to manage PICM.

14.
Vaccines (Basel) ; 12(7)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39066431

RESUMO

Cutaneous leishmaniasis (CL) is a tropical disease endemic in many parts of the world. Characteristic clinical manifestations of CL include the formation of ulcerative skin lesions that can inflict life-long disability if left untreated. Although drugs are available, they are unaffordable and out of reach for individuals who need them the most. Developing a highly cost-efficient CL vaccine could address this problem but such a vaccine remains unavailable. Here, we developed a chimeric influenza virus-like particle expressing the Leishmania amazonensis promastigote surface antigen (LaPSA-VLP). LaPSA-VLPs were self-assembled in Spodoptera frugiperda insect cell lines using the baculovirus expression system. After characterizing the vaccines and confirming successful VLP assembly, BALB/c mice were immunized with these vaccines for efficacy assessment. Sera acquired from mice upon subcutaneous immunization with the LaPSA-VLP specifically interacted with the L. amazonensis soluble total antigens. LaPSA-VLP-immunized mice elicited significantly greater quantities of parasite-specific IgG from the spleens, popliteal lymph nodes, and footpads than unimmunized mice. LaPSA-VLP immunization also enhanced the proliferation of B cell populations in the spleens of mice and significantly lessened the CL symptoms, notably the footpad swelling and IFN-γ-mediated inflammatory response. Overall, immunizing mice with the LaPSA-VLPs prevented mice from developing severe CL symptoms, signifying their developmental potential.

15.
Am J Ophthalmol ; 267: 142-152, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38977151

RESUMO

PURPOSE: To compare the incidence of noninfectious uveitis in skin melanoma or lung cancer patients who received BRAF inhibitors with that in those who received immune checkpoint inhibitors (ICIs) or conventional cytotoxic chemotherapy. DESIGN: Nationwide population-based retrospective clinical cohort study METHODS: From the Health Insurance Review and Assessment Service database of South Korea, we retrospectively defined 77,323 patients with skin melanoma or lung cancer who received BRAF inhibitor therapy (BRAF inhibitor-exposed group; n = 396), ICIs (ICI-exposed group; n = 22,474), or conventional cytotoxic chemotherapy (unexposed group; n = 54,453). We calculated the 1-year cumulative incidence of noninfectious uveitis in each group from the first day of BRAF inhibitor, ICI, or cytotoxic agent administration. RESULTS: During the first year of treatment initiation, the cumulative incidence of uveitis was 0.33%, 0.35%, and 2.27% in the unexposed, ICI-exposed, and BRAF inhibitor-exposed groups, respectively. Adjusted hazard ratios (aHR) indicated a 7.52-fold and 5.68-fold increased risk of uveitis in the BRAF inhibitor-exposed group compared with that in the unexposed and ICI-exposed groups (95% confidence interval [CI] 3.83-14.75, P < .001 and 95% CI 2.81-11.47, P < .001, respectively). After 1:4 propensity score matching, aHRs showed a 35.51-fold and 15.80-fold increased risk (95% CI 4.49-280.48, P = .001 and 95% CI 1.76-141.00, P = .014) of uveitis and severe uveitis, respectively, in the BRAF inhibitor-exposed versus unexposed patients. Crossover analysis within the BRAF inhibitor-exposed group showed a 3.71-fold increase in uveitis risk during 1-year post index date in comparison with 1-year prior to index date (95% CI 1.03-13.40, P = .046). In the BRAF inhibitor-exposed group, female sex, chronic kidney disease, and melanoma were associated with a trend of increased, albeit nonsignificant, risk of uveitis. CONCLUSIONS: Melanoma or lung cancer patients treated with BRAF inhibitors showed significantly higher risk of noninfectious uveitis than patients treated with conventional cytotoxic drugs or ICIs. These findings emphasize the importance of pretreatment patient education on BRAF-inhibitor-associated uveitis risk to enable prompt ophthalmic evaluation and treatment if symptoms arise during drug administration.

16.
Antimicrob Agents Chemother ; 68(9): e0064224, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39082882

RESUMO

Praziquantel (PZQ) is currently the only approved drug for treating clonorchiasis, but its poor efficacy against Clonorchis sinensis larvae has highlighted the need to develop newer drugs. In this study, to address this challenge, we investigated the anti-parasitic efficacy of miltefosine (MLT), curcumin (CUR), and PZQ against C. sinensis metacercariae (CsMC), newly excysted juvenile worms (CsNEJs), and adults. Larvicidal effects of MLT and CUR surpassed those elicited by PZQ in vitro. These two drugs exerted their effect against both CsMC and CsNEJs in a dose- and time-dependent manner. To confirm the effect of these drugs in vivo, Syrian golden hamsters were orally infected with 100 CsMC and subsequently treated with MLT, CUR, or PZQ at 1 and 4 weeks post-infection (wpi). MLT and CUR reduced the worm recoveries at 1 and 4 wpi, indicating that these drugs were efficacious against both larvae and adult C. sinensis. PZQ was only efficacious against adult worms. Interestingly, both MLT and CUR showed lower levels of C. sinensis-specific IgG responses than the infection control group, implying that worm burden and bile IgG responses could be correlated. These results indicate that MLT and CUR are efficacious against both larval and adult stages of C. sinensis, thereby highlighting their potential for further development as alternative therapeutic options for clonorchiasis.


Assuntos
Anti-Helmínticos , Clonorquíase , Clonorchis sinensis , Curcumina , Fosforilcolina , Praziquantel , Animais , Clonorchis sinensis/efeitos dos fármacos , Curcumina/farmacologia , Curcumina/uso terapêutico , Clonorquíase/tratamento farmacológico , Clonorquíase/parasitologia , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapêutico , Fosforilcolina/farmacologia , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/farmacologia , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Mesocricetus , Larva/efeitos dos fármacos , Cricetinae , Masculino , Metacercárias/efeitos dos fármacos
17.
Korean J Ophthalmol ; 38(4): 284-295, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38897593

RESUMO

PURPOSE: To investigate the prognostic factors for recurrent rhegmatogenous retinal detachment following silicone oil removal. METHODS: This retrospective review included 147 consecutive patients with rhegmatogenous retinal detachment treated with silicone oil tamponade at a high-volume referral-based tertiary hospital between January 2012 and May 2022. All patients underwent follow-up for a minimum of 6 months after subsequent silicone oil removal. The primary outcome measure was the rate of recurrent retinal detachment following silicone oil removal, and the secondary outcome was best-corrected visual acuity after silicone oil removal. RESULTS: The mean silicone oil tamponade duration was 4.7 ± 5.01 months (range, 1-38 months; median, 3 months), and the recurrent retinal detachment rate after silicone oil removal was 15.6%. Logistic regression analysis revealed that argon endolaser photocoagulation during silicone oil removal (odds ratio [OR], 0.309; 95% confidence interval [CI], 0.106-0.898; p = 0.031) was associated with a lower rate of anatomical success after silicone oil removal. Demographics, preoperative ocular characteristics, proliferative vitreoretinopathy, previous scleral encircling or buckling, previous retinectomy, concomitant phacoemulsification, duration of silicone oil tamponade, and gas tamponade after silicone oil removal were not significantly associated with recurrent retinal redetachment after silicone oil removal. Duration of silicone oil tamponade (OR, 1.226; 95% CI, 1.073-1.402; p = 0.003) and recurrent retinal detachment after silicone oil removal (OR, 3.400; 95% CI, 1.311-8.817; p = 0.012) were associated with poor visual outcomes after silicone oil removal. CONCLUSIONS: Among all factors examined in this study, including the duration of silicone oil tamponade, laser retinopexy was the only significant prognostic factor for recurrent retinal detachment after silicone oil removal. A longer duration of silicone oil tamponade was associated with worse visual outcomes and a lower rate of visual improvement after silicone oil removal.


Assuntos
Tamponamento Interno , Recidiva , Descolamento Retiniano , Óleos de Silicone , Acuidade Visual , Vitrectomia , Humanos , Descolamento Retiniano/cirurgia , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Estudos Retrospectivos , Masculino , Feminino , Óleos de Silicone/administração & dosagem , Pessoa de Meia-Idade , Prognóstico , Vitrectomia/efeitos adversos , Seguimentos , Adulto , Idoso , Drenagem/métodos , Fotocoagulação a Laser/efeitos adversos , Fotocoagulação a Laser/métodos
18.
Sci Rep ; 14(1): 12769, 2024 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834727

RESUMO

Extracellular fluid (ECF) excess is common in patients with chronic kidney disease (CKD). This study (involving 284 patients with CKD) explored the association between choroidal vascularity index (CVI) and ECF excess. We categorised patients into three groups based on extracellular water/total body water: normal, mildly overhydrated, and severely overhydrated. The more severe ECF status was associated with a lower CVI after adjustment (B = - 0.902, p = 0.001). In non-diabetic patients, both vascular luminal (LA, p < 0.001) and stromal areas (SA, p = 0.003) were significantly reduced in patients with severe ECF excess compared to others, whereas diabetic patients showed no significant differences in LA (p = 0.96) and SA (p = 0.86) based on ECF excess status. These findings suggest that ECF status may influence CVI in patients with CKD, underscoring the need for further research to clarify its direct impact on choroidal changes.


Assuntos
Corioide , Líquido Extracelular , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Feminino , Masculino , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Corioide/metabolismo , Corioide/patologia , Pessoa de Meia-Idade , Líquido Extracelular/metabolismo , Idoso , Tomografia de Coerência Óptica/métodos
20.
Chonnam Med J ; 60(2): 120-128, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38841612

RESUMO

The long-term prognostic significance of maximal infarct transmurality evaluated by contrast-enhanced cardiac magnetic resonance (CE-CMR) in ST-segment elevation myocardial infarction (STEMI) patients has yet to be determined. This study aimed to see if maximal infarct transmurality has any additional long-term prognostic value over other CE-CMR predictors in STEMI patients, such as microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH). The study included 112 consecutive patients who underwent CE-CMR after STEMI to assess established parameters of myocardial injury as well as the maximal infarct transmurality. The primary clinical endpoint was the occurrence of major adverse cardiac events (MACE), which included all-cause death, non-fatal reinfarction, and new heart failure hospitalization. The MACE occurred in 10 patients over a median follow-up of 7.9 years (IQR, 5.8 to 9.2 years) (2 deaths, 3 nonfatal MI, and 5 heart failure hospitalization). Patients with MACE had significantly higher rates of transmural extent of infarction, infarct size >5.4 percent, MVO, and IMH compared to patients without MACE. In stepwise multivariable Cox regression analysis, the transmural extent of infarction defined as 75 percent or more of infarct transmurality was an independent predictor of the MACE after correction for MVO and IMH (hazard ratio 8.7, 95% confidence intervals [CIs] 1.1-71; p=0.043). In revascularized STEMI patients, post-infarction CE-CMR-based maximal infarct transmurality is an independent long-term prognosticator. Adding maximal infarct transmurality to CE-CMR parameters like MVO and IMH could thus identify patients at high risk of long-term adverse outcomes in STEMI.

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