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2.
Case Rep Ophthalmol ; 15(1): 607-613, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39144643

RESUMO

Introduction: Primary vitreoretinal lymphoma (PVRL) is a rare malignant tumor that typically involves the retina, vitreous, or optic nerve head. PVRL often occurs concurrently with central nervous system lymphoma. Here, we present the first report of a patient with biopsy-confirmed PVRL presenting solely with asymptomatic peripheral drusenoid lesions. Case Presentation: A woman in her 70s presented with new elevated amelanotic yellow lesions with overlying pigment in both of her eyes not previously seen prior to cataract surgery. Over the next 4 months, there was waxing and waning of lesions which resolved and first appeared in the right eye and then the left. A diagnostic vitrectomy of the left eye revealed B-cell lymphoma. The patient elected for initial treatment with radiation therapy of both orbits. A new lesion was identified in her right eye nearly 18 months after starting maintenance therapy with ibrutinib, following which systemic chemotherapy with methotrexate was initiated. Conclusion: Elevated clinical suspicion for a malignant process is needed for patients with progressive new retinal lesions in older age. Local radiation therapy to the orbits alone may not be sufficient to prevent progression despite initial presentation showing confinement of disease to the intraocular space.

3.
ACS Nano ; 18(33): 22596-22607, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39132820

RESUMO

The isolation of viruses from complex biological samples is essential for creating sensitive bioassays that assess the efficacy and safety of viral therapeutics and vaccines, which have played a critical role during the COVID-19 pandemic. However, existing methods of viral isolation are time-consuming and labor-intensive due to the multiple processing steps required, resulting in low yields. Here, we introduce the rapid, efficient, and high-resolution acoustofluidic isolation of viruses from complex biological samples via Bessel beam excitation separation technology (BEST). BEST isolates viruses by utilizing the nondiffractive and self-healing properties of 2D, in-plane acoustic Bessel beams to continuously separate cell-free viruses from biofluids, with high throughput and high viral RNA yield. By tuning the acoustic parameters, the cutoff size of isolated viruses can be easily adjusted to perform dynamic, size-selective virus isolation while simultaneously trapping larger particles and separating smaller particles and contaminants from the sample, achieving high-precision isolation of the target virus. BEST was used to isolate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from human saliva samples and Moloney Murine Leukemia Virus from cell culture media, demonstrating its potential use in both practical diagnostic applications and fundamental virology research. With high separation resolution, high yield, and high purity, BEST is a powerful tool for rapidly and efficiently isolating viruses. It has the potential to play an important role in the development of next-generation viral diagnostics, therapeutics, and vaccines.


Assuntos
SARS-CoV-2 , Saliva , SARS-CoV-2/isolamento & purificação , Humanos , Saliva/virologia , COVID-19/virologia , Acústica , Animais , RNA Viral/isolamento & purificação , RNA Viral/genética
5.
Retina ; 44(9): 1478-1485, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39167569

RESUMO

PURPOSE: To investigate associations between quantitative vascular measurements derived from intravenous fluorescein angiography (IVFA) and baseline characteristics on optical coherence tomography (OCT) in neovascular age-related macular degeneration (nAMD) patients. METHODS: The authors prospectively recruited patients with active choroidal neovascularization secondary to AMD over 50 years old, presenting to a single center in Toronto, Canada from 2017 to 2023. Ultra-widefield IVFA images were processed using the artificial intelligence RETICAD FAassist system to extract quantitative information on blood flow, perfusion, and blood-retinal-barrier (BRB) permeability. Associations between IVFA parameters with functional and anatomical outcomes were examined using univariable and multivariable regression models. RESULTS: Eighty-one nAMD eyes and seven healthy control eyes were included. Compared with healthy controls, BRB permeability in the central and peripheral retina was significantly higher in nAMD patients (P < 0.001). On univariable analysis, BRB permeability measured centrally was significantly associated with central macular thickness (P = 0.035), whereas perfusion and blood flow measured centrally were significantly associated with macular volume (P = 0.043 and 0.037, respectively). On multivariable analysis, BRB permeability remained significantly associated with central macular thickness (P = 0.026). CONCLUSION: Central BRB permeability measured on IVFA was significantly associated with baseline central macular thickness in nAMD patients. Future work should longitudinally explore associations between IVFA parameters and clinical characteristics in diverse nAMD populations.


Assuntos
Inteligência Artificial , Angiofluoresceinografia , Vasos Retinianos , Tomografia de Coerência Óptica , Acuidade Visual , Degeneração Macular Exsudativa , Humanos , Masculino , Feminino , Tomografia de Coerência Óptica/métodos , Idoso , Angiofluoresceinografia/métodos , Estudos Prospectivos , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/fisiopatologia , Pessoa de Meia-Idade , Acuidade Visual/fisiologia , Fundo de Olho , Idoso de 80 Anos ou mais , Barreira Hematorretiniana
6.
Ophthalmol Retina ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39182651

RESUMO

PURPOSE: To assess long-term re-detachment rates of the Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT). DESIGN: Randomized controlled trial. SUBJECTS: PIVOT trial participants METHODS: This study was performed at St. Michael's Hospital, Unity Health Toronto, Toronto, Canada. PIVOT trial participants, with a minimum follow-up of two years, who had undergone either pneumatic retinopexy or ppv for rrd repair were assessed for long-term re-detachment by chart review or telephone interview. The latter was the only accepted method for those with less than two years of follow-up. Patients were only eligible if no re-intervention to reattach the retina was performed within the first year of the initial procedure. MAIN OUTCOME MEASURES: Long-term re-detachment rates for pneumatic retinopexy versus ppv following RRD repair. RESULTS: 61 ppv participants and 62 pneumatic retinopexy participants were analyzed. The long-term re-detachment rate was 0% and 1.61% (1/62) in the ppv and pneumatic retinopexy groups, respectively (p= 0.32). The mean follow-up duration in years was 5.43+/-3.60 versus 5.51+/-3.03 in the ppv and pnr groups, respectively. CONCLUSION: There was no statistically significant difference in long-term re-detachment rates for pneumatic retinopexy vs ppv. Both procedures are durable treatment options for rrd over an extended period, rarely requiring additional intervention for re-detachment.

7.
Ophthalmol Sci ; 4(6): 100556, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139542

RESUMO

Purpose: To assess the performance of Chat Generative Pre-Trained Transformer-4 in providing accurate diagnoses to retina teaching cases from OCTCases. Design: Cross-sectional study. Subjects: Retina teaching cases from OCTCases. Methods: We prompted a custom chatbot with 69 retina cases containing multimodal ophthalmic images, asking it to provide the most likely diagnosis. In a sensitivity analysis, we inputted increasing amounts of clinical information pertaining to each case until the chatbot achieved a correct diagnosis. We performed multivariable logistic regressions on Stata v17.0 (StataCorp LLC) to investigate associations between the amount of text-based information inputted per prompt and the odds of the chatbot achieving a correct diagnosis, adjusting for the laterality of cases, number of ophthalmic images inputted, and imaging modalities. Main Outcome Measures: Our primary outcome was the proportion of cases for which the chatbot was able to provide a correct diagnosis. Our secondary outcome was the chatbot's performance in relation to the amount of text-based information accompanying ophthalmic images. Results: Across 69 retina cases collectively containing 139 ophthalmic images, the chatbot was able to provide a definitive, correct diagnosis for 35 (50.7%) cases. The chatbot needed variable amounts of clinical information to achieve a correct diagnosis, where the entire patient description as presented by OCTCases was required for a majority of correctly diagnosed cases (23 of 35 cases, 65.7%). Relative to when the chatbot was only prompted with a patient's age and sex, the chatbot achieved a higher odds of a correct diagnosis when prompted with an entire patient description (odds ratio = 10.1, 95% confidence interval = 3.3-30.3, P < 0.01). Despite providing an incorrect diagnosis for 34 (49.3%) cases, the chatbot listed the correct diagnosis within its differential diagnosis for 7 (20.6%) of these incorrectly answered cases. Conclusions: This custom chatbot was able to accurately diagnose approximately half of the retina cases requiring multimodal input, albeit relying heavily on text-based contextual information that accompanied ophthalmic images. The diagnostic ability of the chatbot in interpretation of multimodal imaging without text-based information is currently limited. The appropriate use of the chatbot in this setting is of utmost importance, given bioethical concerns. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

8.
Ophthalmol Retina ; 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39033924

RESUMO

OBJECTIVE: To compare the efficacy of brolucizumab and aflibercept treatment in reducing the maximum thickness of pigment epithelial detachments (PEDs) and sub-retinal pigment epithelium (sub-RPE) fluid in patients with neovascular age-related macular degeneration in the HAWK and HARRIER studies. DESIGN: HAWK and HARRIER were 96-week, prospective, randomized, double-masked, controlled, multicenter studies. PARTICIPANTS: A total of 1775 patients across 11 countries were included in the HAWK study, and 1048 patients across 29 countries were included in the HARRIER study. INTERVENTION: After 3 monthly loading doses, brolucizumab-treated eyes received injections every 12 weeks or every 8 weeks if disease activity (DA) was detected. Aflibercept-treated eyes received fixed 8-week dosing. MAIN OUTCOME MEASURES: Maximum thickness of PEDs and sub-RPE fluid across the macula were assessed at baseline through week 96 in the brolucizumab- and aflibercept-treated patients and in the patient subgroups with DA at week 16 (matched in terms of injection number and treatment interval). RESULTS: At week 96, there were greater mean percentage reductions from baseline in maximum thickness of both PEDs and sub-RPE fluid in brolucizumab-treated patients vs. aflibercept-treated patients (PED: 19.7% [n = 336] vs. 11.9% [n = 335] in HAWK; 29.5% [n = 364] vs. 18.3% [n = 361] in HARRIER. Sub-RPE fluid: 75.4% vs. 57.3% in HAWK; 86.0% vs. 76.3% in HARRIER). A similar trend in mean percentage reductions was observed in patients with DA at week 16. CONCLUSIONS: This analysis shows that brolucizumab achieved greater reductions in PEDs and sub-RPE fluid thickness than aflibercept in HAWK and HARRIER. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02307682 (HAWK) and NCT02434328 (HARRIER). FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

9.
J Am Heart Assoc ; 13(15): e033350, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39023061

RESUMO

BACKGROUND: Evidence from cohort studies indicates a bidirectional relationship between periodontal disease and type 2 diabetes (T2D), but the underlying mechanisms remain unknown. In this study, we aimed to (1) identify saliva, plasma, and multifluid metabolomic signatures associated with periodontal disease and (2) determine if these signatures predict T2D progression and cardiometabolic biomarkers at year 3. METHODS AND RESULTS: We included participants from the SOALS (San Juan Overweight Adult Longitudinal Study) (n=911). Metabolites from saliva (k=635) and plasma (k=1051) were quantified using liquid chromatography-mass spectrometry. We applied elastic net regression with 10-fold cross-validation to identify baseline metabolomic signatures of periodontal disease. Multivariable Cox proportional hazards regression and linear regression were used to evaluate the association with T2D progression and biomarker concentrations. Metabolomic profiles included highly weighted metabolites related to lysine and pyrimidine metabolism. Periodontal disease or its 3 metabolomic signatures were not associated with T2D progression in 3 years. Prospectively, 1-SD increments in the multifluid and saliva metabolomic signatures were associated with higher low-density lipoprotein (multifluid: 12.9±5.70, P=0.02; saliva: 13.3±5.11, P=0.009). A 1-SD increment in the plasma metabolomic signature was also associated with Homeostatic Model Assessment for Insulin Resistance (2.67±1.14, P=0.02) and triglyceride (0.52±0.18, P=0.002). CONCLUSIONS: Although metabolomic signatures of periodontal disease could not predict T2D progression, they were associated with low-density lipoprotein, triglyceride, and Homeostatic Model Assessment for Insulin Resistance levels at year 3.


Assuntos
Biomarcadores , Diabetes Mellitus Tipo 2 , Progressão da Doença , Dislipidemias , Metabolômica , Obesidade , Doenças Periodontais , Saliva , Humanos , Masculino , Saliva/metabolismo , Saliva/química , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Pessoa de Meia-Idade , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/metabolismo , Dislipidemias/diagnóstico , Biomarcadores/sangue , Doenças Periodontais/sangue , Doenças Periodontais/metabolismo , Doenças Periodontais/diagnóstico , Doenças Periodontais/epidemiologia , Metabolômica/métodos , Obesidade/sangue , Obesidade/metabolismo , Obesidade/complicações , Sobrepeso/sangue , Sobrepeso/metabolismo , Sobrepeso/complicações , Glicemia/metabolismo , Glicemia/análise , Adulto , Hispânico ou Latino , Estudos Longitudinais , Idoso , Estudos Prospectivos
11.
Ophthalmologica ; : 1-14, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38857572

RESUMO

INTRODUCTION: The objective of this study was to examine the association between retinal thickness (RT) fluctuations and best corrected visual acuity (BCVA) in eyes with neovascular AMD, macular edema secondary to RVO, and DME treated with anti-VEGF therapy. METHODS: A systematic search of Ovid MEDLINE, EMBASE, and the Cochrane Library was performed from January 2006 to March 2024. Studies comparing visual or anatomic outcomes of patients treated with anti-VEGF therapy, stratified by magnitudes of RT fluctuation, were included. ROBINS-I and Cochrane RoB 2 tools were used to assess risk of bias, and certainty of evidence was evaluated with GRADE criteria. Meta-analysis was performed with a random-effects model. Primary outcomes were final BCVA and change in BCVA relative to baseline. RESULTS: 15,725 articles were screened; 15 studies were identified in the systematic review and 5 studies were included in the meta-analysis. Final ETDRS VA was significantly worse in eyes with the highest level of RT fluctuation (weighted mean difference [WMD] = 7.86 letters; 95% CI, 4.97, 10.74; p < 0.00001; I2 = 81%; 3,136 eyes). RT at last observation was significantly greater in eyes with high RT fluctuations (WMD = -27.35 µm; 95% CI, -0.04, 54.75; p = 0.05; I2 = 88%; 962 eyes). CONCLUSIONS: Final visual outcome is associated with magnitude of RT fluctuation over the course of therapy. It is unclear whether minimizing RT fluctuations would help optimize visual outcomes in patients treated with anti-VEGF therapy. These findings are limited by a small set of studies, risk of bias, and considerable heterogeneity.

12.
Diabetologia ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38772919

RESUMO

AIMS/HYPOTHESIS: Many studies have examined the relationship between plasma metabolites and type 2 diabetes progression, but few have explored saliva and multi-fluid metabolites. METHODS: We used LC/MS to measure plasma (n=1051) and saliva (n=635) metabolites among Puerto Rican adults from the San Juan Overweight Adults Longitudinal Study. We used elastic net regression to identify plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting baseline HOMA-IR in a training set (n=509) and validated these scores in a testing set (n=340). We used multivariable Cox proportional hazards models to estimate HRs for the association of baseline metabolomic scores predicting insulin resistance with incident type 2 diabetes (n=54) and prediabetes (characterised by impaired glucose tolerance, impaired fasting glucose and/or high HbA1c) (n=130) at 3 years, along with regression from prediabetes to normoglycaemia (n=122), adjusting for traditional diabetes-related risk factors. RESULTS: Plasma, saliva and multi-fluid plasma-saliva metabolomic scores predicting insulin resistance included highly weighted metabolites from fructose, tyrosine, lipid and amino acid metabolism. Each SD increase in the plasma (HR 1.99 [95% CI 1.18, 3.38]; p=0.01) and multi-fluid (1.80 [1.06, 3.07]; p=0.03) metabolomic scores was associated with higher risk of type 2 diabetes. The saliva metabolomic score was associated with incident prediabetes (1.48 [1.17, 1.86]; p=0.001). All three metabolomic scores were significantly associated with lower likelihood of regressing from prediabetes to normoglycaemia in models adjusting for adiposity (HRs 0.72 for plasma, 0.78 for saliva and 0.72 for multi-fluid), but associations were attenuated when adjusting for lipid and glycaemic measures. CONCLUSIONS/INTERPRETATION: The plasma metabolomic score predicting insulin resistance was more strongly associated with incident type 2 diabetes than the saliva metabolomic score. Only the saliva metabolomic score was associated with incident prediabetes.

13.
Nucleic Acids Res ; 52(11): e50, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38797520

RESUMO

Whole-genome bisulfite sequencing (BS-Seq) measures cytosine methylation changes at single-base resolution and can be used to profile cell-free DNA (cfDNA). In plasma, ultrashort single-stranded cfDNA (uscfDNA, ∼50 nt) has been identified together with 167 bp double-stranded mononucleosomal cell-free DNA (mncfDNA). However, the methylation profile of uscfDNA has not been described. Conventional BS-Seq workflows may not be helpful because bisulfite conversion degrades larger DNA into smaller fragments, leading to erroneous categorization as uscfDNA. We describe the '5mCAdpBS-Seq' workflow in which pre-methylated 5mC (5-methylcytosine) single-stranded adapters are ligated to heat-denatured cfDNA before bisulfite conversion. This method retains only DNA fragments that are unaltered by bisulfite treatment, resulting in less biased uscfDNA methylation analysis. Using 5mCAdpBS-Seq, uscfDNA had lower levels of DNA methylation (∼15%) compared to mncfDNA and was enriched in promoters and CpG islands. Hypomethylated uscfDNA fragments were enriched in upstream transcription start sites (TSSs), and the intensity of enrichment was correlated with expressed genes of hemopoietic cells. Using tissue-of-origin deconvolution, we inferred that uscfDNA is derived primarily from eosinophils, neutrophils, and monocytes. As proof-of-principle, we show that characteristics of the methylation profile of uscfDNA can distinguish non-small cell lung carcinoma from non-cancer samples. The 5mCAdpBS-Seq workflow is recommended for any cfDNA methylation-based investigations.


Assuntos
5-Metilcitosina , Ácidos Nucleicos Livres , Ilhas de CpG , Metilação de DNA , DNA de Cadeia Simples , Humanos , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , DNA de Cadeia Simples/metabolismo , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/sangue , 5-Metilcitosina/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangue , Sulfitos/química , Regiões Promotoras Genéticas , Análise de Sequência de DNA/métodos , Sequenciamento Completo do Genoma/métodos
14.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167168, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38641012

RESUMO

OBJECTIVES: Testing for anti-SSA/Ro antibodies in serum is essential in the diagnostic work-up for primary Sjögren's syndrome (pSS). In this study, we aimed to validate our previous assay for detection of salivary anti-SSA/Ro52, and to develop assays for detection of salivary anti-SSA/Ro60 and for detection of anti-Ro52 and -Ro60 in plasma using the electric field-induced release and measurement (EFIRM) platform. METHODS: Whole saliva samples from two independent Danish cohorts (DN1 and DN2) including 49 patients with pSS, 73 patients with sicca symptoms, but not fulfilling the classification criteria for pSS (non-pSS sicca), and 51 healthy controls (HC), as well as plasma samples from the DN1 cohort were analyzed using EFIRM to detect anti-SSA/Ro52 and -Ro60. RESULTS: In the DN1 cohort, 100 % in the pSS group and 16 % in the non-pSS sicca group were serum anti-SSA/Ro positive by ELISA. EFIRM detected anti-SSA (Ro52 and/or -Ro60) in plasma and saliva in 100 % and 96 % patients with pSS, and 16 % and 29 % with non-pSS sicca. In the DN2 cohort, 80 % patients with pSS and 26 % with non-pSS sicca were serum anti-SSA/Ro positive. Salivary anti-SSA discriminated patients with pSS from HC and non-pSS sicca with an AUC range of 0.74-0.96 in the DN1 and DN2 cohorts. EFIRM discriminated pSS from non-pSS sicca with an AUC of 0.98 in plasma. CONCLUSION: Our findings suggest that salivary anti-SSA/Ro antibodies are potential discriminatory biomarkers for pSS, which may also identify seronegative patients, addressing the unmet clinical need of early detection and stratification of pSS.


Assuntos
Ribonucleoproteínas , Saliva , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/sangue , Saliva/imunologia , Saliva/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Ribonucleoproteínas/imunologia , Adulto , Idoso , Anticorpos Antinucleares/sangue , Anticorpos Antinucleares/imunologia , Estudos de Casos e Controles , Autoanticorpos/sangue , Autoanticorpos/imunologia , Ensaio de Imunoadsorção Enzimática , Autoantígenos , RNA Citoplasmático Pequeno
15.
RMD Open ; 10(2)2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599651

RESUMO

OBJECTIVE: Primary Sjögren's syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva. METHODS: Using a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls. RESULTS: Saliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001) CONCLUSIONS: Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.


Assuntos
Saliva , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/diagnóstico , Imunoglobulina A , Autoanticorpos , Imunoglobulina G
16.
Front Oncol ; 14: 1332004, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38511142

RESUMO

In clinical oncology, cell-free DNA (cfDNA) has shown immense potential in its ability to noninvasively detect cancer at various stages and monitor the progression of therapy. Despite the rapid improvements in cfDNA liquid biopsy approaches, achieving the required sensitivity to detect rare tumor-derived cfDNA still remains a challenge. For next-generation sequencing, the perceived presentation of cfDNA is strongly linked to the extraction and library preparation protocols. Conventional double-stranded DNA library preparation (dsDNA-LP) focuses on assessing ~167bp double-stranded mononucleosomal (mncfDNA) and its other oligonucleosomal cell-free DNA counterparts in plasma. However, dsDNA-LP methods fail to include short, single-stranded, or nicked DNA in the final library preparation, biasing the representation of the actual cfDNA populations in plasma. The emergence of single-stranded library preparation (ssDNA-LP) strategies over the past decade has now allowed these other populations of cfDNA to be studied from plasma. With the use of ssDNA-LP, single-stranded, nicked, and ultrashort cfDNA can be comprehensively assessed for its molecular characteristics and clinical potential. In this review, we overview the current literature on applications of ssDNA-LP on plasma cfDNA from a potential cancer liquid biopsy perspective. To this end, we discuss the molecular principles of single-stranded DNA adapter ligation, how library preparation contributes to the understanding of native cfDNA characteristics, and the potential for ssDNA-LP to improve the sensitivity of circulating tumor DNA detection. Additionally, we review the current literature on the newly reported species of plasma ultrashort single-stranded cell-free DNA plasma, which appear biologically distinct from mncfDNA. We conclude with a discussion of future perspectives of ssDNA-LP for liquid biopsy endeavors.

18.
JAMA Ophthalmol ; 142(4): 321-326, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38421670

RESUMO

Importance: Ophthalmology is reliant on effective interpretation of multimodal imaging to ensure diagnostic accuracy. The new ability of ChatGPT-4 (OpenAI) to interpret ophthalmic images has not yet been explored. Objective: To evaluate the performance of the novel release of an artificial intelligence chatbot that is capable of processing imaging data. Design, Setting, and Participants: This cross-sectional study used a publicly available dataset of ophthalmic cases from OCTCases, a medical education platform based out of the Department of Ophthalmology and Vision Sciences at the University of Toronto, with accompanying clinical multimodal imaging and multiple-choice questions. Across 137 available cases, 136 contained multiple-choice questions (99%). Exposures: The chatbot answered questions requiring multimodal input from October 16 to October 23, 2023. Main Outcomes and Measures: The primary outcome was the accuracy of the chatbot in answering multiple-choice questions pertaining to image recognition in ophthalmic cases, measured as the proportion of correct responses. χ2 Tests were conducted to compare the proportion of correct responses across different ophthalmic subspecialties. Results: A total of 429 multiple-choice questions from 136 ophthalmic cases and 448 images were included in the analysis. The chatbot answered 299 of multiple-choice questions correctly across all cases (70%). The chatbot's performance was better on retina questions than neuro-ophthalmology questions (77% vs 58%; difference = 18%; 95% CI, 7.5%-29.4%; χ21 = 11.4; P < .001). The chatbot achieved a better performance on nonimage-based questions compared with image-based questions (82% vs 65%; difference = 17%; 95% CI, 7.8%-25.1%; χ21 = 12.2; P < .001).The chatbot performed best on questions in the retina category (77% correct) and poorest in the neuro-ophthalmology category (58% correct). The chatbot demonstrated intermediate performance on questions from the ocular oncology (72% correct), pediatric ophthalmology (68% correct), uveitis (67% correct), and glaucoma (61% correct) categories. Conclusions and Relevance: In this study, the recent version of the chatbot accurately responded to approximately two-thirds of multiple-choice questions pertaining to ophthalmic cases based on imaging interpretation. The multimodal chatbot performed better on questions that did not rely on the interpretation of imaging modalities. As the use of multimodal chatbots becomes increasingly widespread, it is imperative to stress their appropriate integration within medical contexts.


Assuntos
Glaucoma , Oftalmologia , Criança , Humanos , Inteligência Artificial , Estudos Transversais , Retina
19.
J Surg Res ; 296: 10-17, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38181644

RESUMO

INTRODUCTION: Few studies have examined the use of ibutilide in noncardiac surgical populations. Our study considered the effectiveness and safety of ibutilide in cardioversion of atrial fibrillation (AF) in medical and surgical intensive care patients. METHODS: A retrospective chart review was performed for patients with a confirmed diagnosis of AF who were hemodynamically stable and received ibutilide after the initial diagnosis. Patients were administered 1 mg of ibutilide fumarate intravenous for 10 min with a second dose administered if AF persisted after 30 min. Patients were pretreated with intravenous magnesium sulfate if their blood magnesium level was <2 mg/dL. RESULTS: Fifty seven total female patients and 99 male patients received ibutilide. Females had an 88% conversion rate to normal sinus rhythm (NSR) compared to 68% in males (P = 0.008). A 70% successful return to NSR was observed in patients from all groups pretreated with magnesium sulfate (P = 0.045). One year after discharge, 74% of the patients stayed in the NSR. CONCLUSIONS: Within our population, pretreatment with magnesium sulfate followed by ibutilide was associated with increased conversion to NSR. Additionally, we noted that females had a higher conversion rate to NSR compared to males, regardless of whether they were pretreated with magnesium sulfate.


Assuntos
Fibrilação Atrial , Flutter Atrial , Sulfonamidas , Humanos , Masculino , Feminino , Fibrilação Atrial/tratamento farmacológico , Antiarrítmicos/efeitos adversos , Sulfato de Magnésio/efeitos adversos , Cardioversão Elétrica , Estudos Retrospectivos , Fatores Sexuais , Flutter Atrial/tratamento farmacológico , Resultado do Tratamento
20.
Br J Ophthalmol ; 108(9): 1263-1268, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-38290803

RESUMO

BACKGROUND: The purpose of the study is to compare visual acuity, complications and outer retinal integrity following subretinal fluid (SRF) drainage from the peripheral retinal breaks (PRBs) versus posterior retinotomy (PR) versus perfluorocarbon liquid (PFCL) for macula-off rhegmatogenous retinal detachments (RRDs) at 2 years post-surgery. METHODS: Retrospective analysis of 300 consecutive patients with primary RRD undergoing 23-gauge pars plana vitrectomy with SRF drainage through (1) PRB (n=100), (2) PR (n=100) or (3) with PFCL (n=100). Primary outcomes were visual acuity (best-corrected visual acuity (BCVA)) and complications (cystoid macular oedema (CMO) and epiretinal membrane (ERM)). Secondary outcomes were discontinuity of the external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IDZ) at 2 years post-surgery. RESULTS: Mean (±SD) logMAR BCVA at 24 months was better in the PRB compared with PR and PFCL, with PFCL having the worst BCVA (PRB 0.5±0.6; PR 0.7±0.5; PFCL 0.9±0.7, p=0.001). CMO was higher with PFCL (PRB 29.7%; PR 30.2%; PFCL 45.9%, p=0.0015) and ERM formation was higher in PR (PRB 62.6%; PR 93.0%; PFCL 68.9%, p=0.002). There were no differences in ELM or EZ discontinuity. However, IDZ discontinuity was higher in PFCL (PRB 34%; PR 27%; PFCL 46%, p=0.002) at 2 years. CONCLUSIONS: Visual acuity was worse and discontinuity of the IDZ and CMO was greater in eyes with PFCL-assisted drainage compared with PRB or PR. Drainage technique may impact long-term visual acuity and photoreceptor integrity.


Assuntos
Drenagem , Fóvea Central , Descolamento Retiniano , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Descolamento Retiniano/cirurgia , Descolamento Retiniano/fisiopatologia , Acuidade Visual/fisiologia , Estudos Retrospectivos , Feminino , Masculino , Drenagem/métodos , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Fluorocarbonos/administração & dosagem , Seguimentos
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