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1.
J Med Virol ; 96(5): e29521, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38727013

RESUMO

Methylation panels, tools for investigating epigenetic changes associated with diseases like cancer, can identify DNA methylation patterns indicative of disease, providing diagnostic or prognostic insights. However, the application of methylation panels focusing on the sex-determining region Y-box 1 (SOX1) and paired box gene 1 (PAX1) genes for diagnosing cervical lesions is under-researched. This study aims to examine the diagnostic performance of PAX1/SOX1 gene methylation as a marker for cervical precancerous lesions and its potential application in triage diagnosis. From September 2022 to April 2023, 181 patients with abnormal HPV-DNA tests or cytological exam results requiring colposcopy were studied at Hubei Maternal and Child Health Hospital, China. Data were collected from colposcopy, cytology, HPV-DNA tests, and PAX1/SOX1 methylation detection. Patients were categorized as control, cervical intraepithelial neoplasia Grade 1 (CIN1), Grade 2 (CIN2), Grade 3 (CIN3), and cervical cancer (CC) groups based on histopathology. We performed HPV testing, liquid-based cytology, and PAX1/SOX1 gene methylation testing. We evaluated the diagnostic value of methylation detection in cervical cancer using DNA methylation positivity rate, sensitivity, specificity, and area under the curve (AUC), and explored its potential for triage diagnosis. PAX1/SOX1 methylation positivity rates were: control 17.1%, CIN1 22.5%, CIN2 100.0%, CIN3 90.0%, and CC 100.0%. The AUC values for PAX1 gene methylation detection in diagnosing CIN1+, CIN2+, and CIN3+ were 0.52 (95% confidence interval [CI]: 0.43-0.62), 0.88 (95% CI: 0.80-0.97), and 0.88 (95% CI: 0.75-1.00), respectively. Corresponding AUC values for SOX1 gene methylation detection were 0.47 (95% CI: 0.40-0.58), 0.80 (95% CI: 0.68-0.93), and 0.92 (95% CI: 0.811-1.00), respectively. In HPV16/18-negative patients, methylation detection showed sensitivity of 32.4% and specificity of 83.7% for CIN1+. For CIN2+ and CIN3+, sensitivity was all 100%, with specificities of 83.0% and 81.1%. Among the patients who underwent colposcopy examination, 166 cases had cytological examination results ≤ASCUS, of which 37 cases were positive for methylation, and the colposcopy referral rate was 22.29%. PAX1/SOX1 gene methylation detection exhibits strong diagnostic efficacy for cervical precancerous lesions and holds significant value in triage diagnosis.


Assuntos
Metilação de DNA , Fatores de Transcrição Box Pareados , Infecções por Papillomavirus , Fatores de Transcrição SOXB1 , Triagem , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Fatores de Transcrição SOXB1/genética , Adulto , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/virologia , Pessoa de Meia-Idade , Triagem/métodos , Fatores de Transcrição Box Pareados/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/genética , Sensibilidade e Especificidade , Biomarcadores Tumorais/genética , China , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/genética , Adulto Jovem , Detecção Precoce de Câncer/métodos , Colposcopia
2.
Ophthalmol Retina ; 8(2): 126-136, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37673395

RESUMO

PURPOSE: To explore the risk factors and fundus imaging features of vitamin A deficiency retinopathy (VADR) in an academic tertiary referral center in Atlanta, GA, United States, and to propose guidance regarding diagnostic workup and management of affected patients. DESIGN: Single-center retrospective case series. SUBJECTS: Nine patients seen between 2015 and 2021 at the Emory Eye Center diagnosed with VADR. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Baseline serum retinol level, Snellen visual acuity, multimodal fundus imaging findings, and electroretinography findings. RESULTS: Nine patients, 4 (44.4%) female, with a median (range) age of 68 (50-75) years were identified. The most common underlying etiologies for vitamin A deficiency included history of gastrointestinal surgery (55.6%), liver disease (44.4%), and nutritional depletion due to low-quality diet (44.4%). Only 1 (11.1%) patient had a history of bariatric surgery. Four (44.4%) patients were on some form of vitamin A supplementation before the diagnosis of VADR. Median (range) serum retinol level was 0.06 (< 0.06-0.19) mg/L. All patients had macular subretinal hyperreflective deposits resembling subretinal drusenoid deposits, although in some cases, these were scant and sparsely distributed. Six eyes of 3 patients with longstanding deficiency had defects in the external limiting membrane (ELM). Three of these eyes additionally had macular areas of complete retinal pigment epithelium and outer retinal atrophy (cRORA). Full-field electroretinography demonstrated severe rod dysfunction and mild to moderate cone system dysfunction. Many findings of VADR were reversible with vitamin A repletion. However, all eyes with ELM defects or cRORA had persistence or continued growth of these lesions. CONCLUSION: Vitamin A deficiency retinopathy is uncommon in the developed world. However, given that early intervention can lead to dramatic visual improvement and avoid potentially permanent retinal damage, retina specialists should be familiar with its clinical presentation. The presence of nyctalopia and subretinal hyperreflective deposits in a patient with a history of gastrointestinal surgery, liver disease, and/or poor diet can be suggestive of this diagnosis, even in the presence of ongoing vitamin A supplementation. Vitamin A supplementation can vary in route and dosage and can be tailored to the individual with serial testing of serum retinol. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.


Assuntos
Hepatopatias , Degeneração Retiniana , Deficiência de Vitamina A , Humanos , Feminino , Estados Unidos/epidemiologia , Idoso , Masculino , Vitamina A , Deficiência de Vitamina A/complicações , Deficiência de Vitamina A/diagnóstico , Estudos Retrospectivos , Centros de Atenção Terciária , Angiofluoresceinografia/métodos
3.
J Vitreoretin Dis ; 7(6): 504-509, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37974918

RESUMO

Purpose: To investigate whether any systemic medical conditions may be associated with a higher risk for developing postinjection endophthalmitis. Methods: This case-control study is a retrospective review within the Emory Eye Center from 2009 to 2019 and The Cleveland Clinic Foundation from 2012 to 2019. Each case was matched in a 1:4 case-to-control ratio. The associations between medical comorbidities and endophthalmitis were explored using multivariable logistic regression models on the combined sample. Results: Sixty-six individuals were diagnosed with injection-associated endophthalmitis. Systemic immunocompromised status was found to be a risk factor associated with developing endophthalmitis with an adjusted odds ratio (aOR) of 3.17 (P = .009). Other conditions with increased risk approaching statistical significance included a history of pulmonary disease (aOR, 1.74; P = .08) and a history of smoking (aOR, 1.72; P = .06). Conclusions: This is the first report to our knowledge demonstrating that immunocompromised status is associated with an increased risk for developing postinjection endophthalmitis. While this study may be limited due to its retrospective nature, the result may nevertheless serve as a guidance for risk counseling. Future analysis using a large-scale database will be needed.

4.
J Natl Cancer Cent ; 2(4): 291-297, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36532841

RESUMO

Necroptosis is currently attracting the attention of the scientific community for its broad implications in inflammatory diseases and cancer. However, detecting ongoing necroptosis in vivo under both experimental and clinical disease conditions remains challenging. The technical barrier lies in four aspects, namely tissue sampling, real-time in vivo monitoring, specific markers, and distinction between different types of cell death. In this review, we presented the latest methodological advances for in vivo necroptosis identification. The advances highlighted the multi-parameter flow cytometry, sA5-YFP tool, radiolabeled Annexin V/Duramycin, Gallium-68-labeled IRDye800CW contrast agent, and SMART platform in vivo. We also discussed the up-to-date research models in studying necroptosis, particularly the mice models for manipulating and monitoring necroptosis. Based on these recent advances, this review aims to provide some advice on current necroptosis techniques and approaches.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36007259

RESUMO

BACKGROUND/PURPOSE: To report an atypical presentation of postoperative endophthalmitis after cataract surgery that initially presented as angle-closure glaucoma and to discuss challenges with the case management due to the unusual presentation and patient non-compliance. METHODS: Observational case report. B-scan ultrasound and ultrasound biomicroscopy. RESULTS: A 69-year-old Caucasian male with a 1-week history of uncomplicated cataract surgery was referred to our glaucoma clinic due to vision loss and concern for angle closure glaucoma. Anterior segment exam showed 360 degrees of flat anterior chamber (AC) with no hypopyon. A diagnosis of postoperative endophthalmitis was established when a B-scan ultrasound showed dense vitreous opacities. The patient underwent a pars plana vitrectomy (PPV), AC reformation, peripheral iridectomy, and intravitreal injection of antibiotics for treatment of endophthalmitis in the presence of an angle-closure glaucoma with good visual recovery. CONCLUSION: A low threshold for suspicion of endophthalmitis is needed after any routine intraocular procedure. An atypical presentation may masquerade as another pathology that delays the true diagnosis and treatment. Timely intervention in postoperative endophthalmitis is crucial in preserving vision.

6.
Ophthalmic Surg Lasers Imaging Retina ; 53(3): 132-138, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35272560

RESUMO

BACKGROUND AND OBJECTIVE: To provide an overview of progressive retinoschisis-related retinal detachment (RSRD) management at a tertiary referral center. MATERIALS AND METHODS: Single-institution retrospective case series from January 1, 2003, to May 1, 2020. RESULTS: Progressive RSRD occurred in 0.9% of patients with retinoschisis. Mean (range) age at time of surgery was 58.7 years (40.0 to 74.0). Ten eyes were initially treated with scleral buckle, three eyes with vitrectomy, and three eyes with combined scleral buckle and vitrectomy. Overall reattachment rate was 100.0%; single-surgery success was 56.2%. Proliferative vitreoretinopathy developed in 10.0% of scleral buckles, 33.3% of vitrectomies, and 33.3% of combined surgeries. CONCLUSIONS: Progressive RSRD is rare and poses surgical management challenges. Final retinal attachment can be achieved successfully but often requires secondary and staged surgeries. Localization of outer retinal breaks may help guide surgical management. Further research-such as a large-scale, prospective, multicenter, randomized trial-would be needed to determine the optimal surgical technique. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:132-138.].


Assuntos
Descolamento Retiniano , Retinosquise , Humanos , Estudos Prospectivos , Retina , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Descolamento Retiniano/cirurgia , Retinosquise/diagnóstico , Retinosquise/etiologia , Retinosquise/cirurgia , Estudos Retrospectivos , Recurvamento da Esclera/métodos , Resultado do Tratamento , Acuidade Visual , Vitrectomia/métodos
8.
Trends Cancer ; 8(1): 21-27, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34627742

RESUMO

Necroptosis, a form of programmed necrotic cell death, is a gatekeeper of host defense against certain pathogen invasions. The deregulation of necroptosis is also a key factor of many inflammatory diseases. Recent studies have revealed an important role of necroptosis in tumorigenesis and metastasis and imply the potential of targeting necroptosis as a novel cancer therapy. While its molecular mechanism has been well studied, details of the regulation and function of necroptosis of tumor cells in tumorigenesis and metastasis only began to emerge recently, and we discuss these herein.


Assuntos
Necroptose , Proteína Serina-Treonina Quinases de Interação com Receptores , Apoptose/genética , Humanos , Necroptose/genética , Necrose , Proteínas Quinases/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
9.
J Mol Diagn ; 23(12): 1774-1786, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34562613

RESUMO

Although most small B-cell lymphomas (SBCLs) can be diagnosed using routine methods, challenges exist. For example, marginal zone lymphomas (MZLs) can be difficult to rule-in, in large part because no widely-used, sensitive, and specific biomarker is available for the marginal zone cell of origin. In this study, it was hypothesized that DNA methylation array profiling can assist with the classification of SBCLs, including MZLs. Extramedullary SBCLs, including challenging cases, were reviewed internally for pathology consensus and profiled. By combining the resulting array data set with data sets from other groups, a set of 26 informative probes was selected and used to train machine learning models to classify 4 common SBCLs: chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, and MZL. Prediction probability cutoff was used to separate classifiable from unclassifiable cases, and show that the trained model was able to classify 95% of independent test cases (n = 264/279). The concordance between model predictions and pathology diagnoses was 99.6% (n = 262/263) among classifiable test cases. One validation reference test case was reclassified based on model prediction. The model was also used to predict the diagnoses of two challenging SBCLs. Although the differential examined and data on difficult cases are limited, these results support accurate methylation-based classification of SBCLs. Furthermore, high specificities of predictions suggest that methylation signatures can be used to rule-in MZLs.


Assuntos
Metilação de DNA , Linfoma de Células B/genética , Linfoma de Células B/patologia , Idoso , Biomarcadores Tumorais/genética , Feminino , Humanos , Linfonodos/patologia , Linfoma de Células B/classificação , Linfoma de Células B/cirurgia , Linfoma de Zona Marginal Tipo Células B/genética , Linfoma de Zona Marginal Tipo Células B/cirurgia , Pessoa de Meia-Idade , Modelos Biológicos , Estudo de Prova de Conceito , Reprodutibilidade dos Testes
10.
Nat Commun ; 12(1): 2666, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976222

RESUMO

Tumor necrosis happens commonly in advanced solid tumors. We reported that necroptosis plays a major role in tumor necrosis. Although several key necroptosis regulators including receptor interacting protein kinase 1 (RIPK1) have been identified, the regulation of tumor necroptosis during tumor development remains elusive. Here, we report that Z-DNA-binding protein 1 (ZBP1), not RIPK1, mediates tumor necroptosis during tumor development in preclinical cancer models. We found that ZBP1 expression is dramatically elevated in necrotic tumors. Importantly, ZBP1, not RIPK1, deletion blocks tumor necroptosis during tumor development and inhibits metastasis. We showed that glucose deprivation triggers ZBP1-depedent necroptosis in tumor cells. Glucose deprivation causes mitochondrial DNA (mtDNA) release to the cytoplasm and the binding of mtDNA to ZBP1 to activate MLKL in a BCL-2 family protein, NOXA-dependent manner. Therefore, our study reveals ZBP1 as the key regulator of tumor necroptosis and provides a potential drug target for controlling tumor metastasis.


Assuntos
Neoplasias da Mama/genética , Necroptose/genética , Proteínas de Ligação a RNA/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Células HEK293 , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Knockout , Camundongos Nus , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Proteínas de Ligação a RNA/metabolismo , Terapêutica com RNAi/métodos , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
11.
Ophthalmic Surg Lasers Imaging Retina ; 52(2): 107-109, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33626172

RESUMO

Jeune syndrome is a rare skeletal dysplasia with an associated retinal dystrophy. The authors describe a case of progressive bilateral macular atrophy (with multimodal imaging) in a patient with Jeune syndrome who was followed over 13 years. This case, confirmed with genetic testing, highlights the importance of characterizing the relationship between phenotype and genotype in this genetically heterogenous condition. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:107-109.].


Assuntos
Síndrome de Ellis-Van Creveld , Degeneração Macular , Atrofia , Humanos , Imagem Multimodal
12.
Ophthalmol Retina ; 5(9): 901-909, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33271346

RESUMO

PURPOSE: The mainstay empiric treatments of bacterial endophthalmitis are intravitreal vancomycin and ceftazidime. In the United States, up to 10% of the general population has a reported penicillin (PCN) allergy. Despite low cross-reactivity between PCN and later-generation cephalosporins, some providers alter the intravitreal antibiotic choice for endophthalmitis because of concern for allergic reactions. We evaluated the management strategies of infectious endophthalmitis in the setting of self-reported systemic antibiotic allergies and the association with adverse reactions after standard intravitreal antibiotic administration. DESIGN: Single-center, retrospective cohort study. PARTICIPANTS: All patients with endophthalmitis between 2005 and 2019 and documented PCN, PCN-analog, cephalosporin, or vancomycin allergy who received intravitreal antibiotics on the basis of International Classification of Diseases 9th and 10th Revisions, and Current Procedural Terminology codes. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Any allergic reaction after intravitreal injection, additional surgical interventions required for treatment, and visual function at last recorded visit. RESULTS: Of the 65 patients included in this cohort, the most common causes of endophthalmitis were postcataract extraction surgery (n = 23, 35.4%) and postintravitreal injection (n = 11, 16.9%). All patients (65/65) received intravitreal vancomycin, and 81.5% (53/65) received intravitreal ceftazidime. Of the 53 patients who received intravitreal ceftazidime, 46 (86.8%) had allergies to PCNs alone, 5 (9.4%) had a cephalosporin allergy alone, and 2 (3.8%) had reported allergies to both PCN and cephalosporin antibiotics. Two patients (3.1%) with a documented vancomycin allergy received intravitreal vancomycin without complication. No patients exhibited any systemic or local allergic reactions or complications after intravitreal injection. CONCLUSIONS: There were no documented allergic reactions in this cohort of patients with systemic antibiotic allergies who were treated for infectious endophthalmitis. Our findings are consistent with previous reports of a low allergic cross-reactivity between PCN and later-generation cephalosporins. Ophthalmologists should use evidence-based practices and a careful informed consent process when choosing intravitreal antibiotics for patients with specific antibiotic allergies. In the routine patient with suspected bacterial endophthalmitis, PCN allergy may not be an absolute contraindication to intravitreal cephalosporin use.


Assuntos
Cefalosporinas/uso terapêutico , Hipersensibilidade a Drogas , Endoftalmite/tratamento farmacológico , Infecções Oculares Bacterianas/tratamento farmacológico , Penicilinas/uso terapêutico , Vancomicina/uso terapêutico , Idoso , Antibacterianos/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
13.
Acta Pharm Sin B ; 10(2): 197-206, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32082968

RESUMO

Pregnane X receptor (PXR, NR1I2) is a prototypical member of the nuclear receptor superfamily. PXR can be activated by both endobiotics and xenobiotics. As a key xenobiotic receptor, the cellular function of PXR is mostly exerted by its binding to the regulatory gene sequences in a ligand-dependent manner. Classical downstream target genes of PXR participate in xenobiotic responses, such as detoxification, metabolism and inflammation. Emerging evidence also implicates PXR signaling in the processes of apoptosis, cell cycle arrest, proliferation, angiogenesis and oxidative stress, which are closely related to cancer. Here, we discussed, in addition to the characterization of PXR per se, the biological function and regulatory mechanism of PXR signaling in cancer, and its potential for the targeted prevention and therapeutics.

14.
Zhongguo Zhong Yao Za Zhi ; 45(23): 5722-5731, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33496112

RESUMO

This paper was to investigate the effect of total flavonoids of Lichi Semen(TFL) on carbon tetrachloride(CCl_4)-induced liver fibrosis in rats, analyze and predict its mechanism of action and potential quality markers(Q-marker). Firstly, male SD rats were taken and injected subcutaneously with a 40% CCl_4-vegetable oil solution twice a week for 8 consecutive weeks to establish a rat model of liver fibrosis. The rats with liver fibrosis were randomly divided into model group, silybin group(43.19 mg·kg~(-1)), Fuzheng Huayu Capsules group(462.75 mg·kg~(-1)), and TFL groups(100 mg·kg~(-1) and 25 mg·kg~(-1)), with normal rats as a blank group, 10 rats in each group. Except for the blank group, the rats in the other groups were subcutaneously injected with 40% CCl_4-vegetable oil solution of a maintenance dose, once a week. The rats in various treatment groups received corresponding doses of drugs, while the rats in the blank group and model group received the same volume of normal saline once a day for 4 weeks. At the end of the experiment, blood was collected from the abdominal aorta and the liver tissues were collected. The levels of total bilirubin(TBiL), direct bilirubin(DBiL), indirect bilirubin(IBiL), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum were detected by using an automatic biochemical detector. Masson staining was used to observe the histopathological changes of rat liver. Then, the chemical compositions of TFL were collected, and the action targets of these chemical compositions were predicted through SWISS database and reverse molecular docking server(DRAR-CPI). After screening of disease targets of liver fibrosis by Gene Cards database, the protein-protein interaction was analyzed with use of STRING database, and GO(gene ontology) analysis and KEGG(Kyoto encyclopedia of genes and genomes) enrich analysis were also carried out. Moreover, an iTRAQ proteomics technology was used to determine protein expression in liver tissues of rats in TFL, model and blank groups to verify the targets. Furthermore, Cytoscape software was used to establish and visualize the network of chemical components, targets and pathways, and predict the potential Q-marker of TFL. The results showed that the levels of TBiL, DBiL, IBiL, ALT, and AST in the model group were significantly higher than those in the blank normal group(P<0.05), and the above levels in the treatment groups were lower than those in the model group, but with no significant differences. Masson staining showed that the liver damage and the degree of fibrosis were severe in the model group, and were relieved to different degrees in the treatment groups. Then, 74 chemical components were screened, which could act on 865 targets such as EGFR and SRC, participating in the regulation of cancer pathways, PI3 K-Akt signaling pathway, HIF-1 signaling pathway and other signaling pathways closely related to liver fibrosis. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin showed the highest correlation with liver fibrosis-related targets and pathways. Proteomics results showed that a total of 18 proteins among the 45 proteins predicted by internet pharmacology were identified, among which 6 proteins were significantly expressed, including 5 up-regulated proteins and 1 down-regulated protein. The protein expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1 was significantly returned to a normal state in the TFL treatment groups. In conclusion, TFL may demonstrate the anti-hepatic fibrosis and potential hepatoprotective effects by regulating the expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1, which may be associated with the regulation of multiple signaling pathways related to liver fibrosis such as PI3 K-Akt pathway. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin could be regarded as potential Q-markers of TFL for quality control.


Assuntos
Flavonoides , Sêmen , Animais , Tetracloreto de Carbono , Fígado/patologia , Cirrose Hepática , Masculino , Simulação de Acoplamento Molecular , Ratos , Ratos Sprague-Dawley
15.
JIMD Rep ; 49(1): 37-42, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31788408

RESUMO

Congenital neutropenias due to mutations in ELANE, SBDS or HAX1 or in the setting of glycogen storage disease (GSD) which is caused by SLC37A4 mutation, often require prolonged granulocyte colony stimulating factor (G-CSF) therapy to prevent recurrent infections and hospital admission. There has been emerging evidence that prolonged exposure to G-CSF in cases with congenital neutropenia other than GSD is associated with transformation to myelodysplastic syndrome/acute myeloid leukemia.

16.
JAMA Ophthalmol ; 137(11): 1275-1282, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31486843

RESUMO

IMPORTANCE: A unique pigmentary maculopathy was recently described in 6 patients with long-term exposure to pentosan polysulfate sodium (PPS), a long-standing oral therapy for interstitial cystitis. OBJECTIVE: To characterize the exposure characteristics and clinical manifestations of PPS-associated maculopathy. DESIGN, SETTING, AND PARTICIPANTS: In this multi-institutional case series, medical records of patients who exhibited the characteristic maculopathy in the setting of prior PPS exposure were retrospectively reviewed. Data were collected from August 1, 2012, to October 1, 2018, and data were analyzed from October 2018 to January 2019. MAIN OUTCOMES AND MEASURES: Drug exposure, visual acuity, and retinal imaging characteristics. RESULTS: Of the 35 included patients (70 eyes), 34 (97%) were female, and the median (range) age was 60 (37-79) years. The median (range) duration of PPS intake was 15 (3-22) years, and the median (range) cumulative exposure was 1.61 (0.44-4.31) kg. The leading visual symptoms were metamorphopsia, blurred vision, and prolonged dark adaptation. Median (range) logMAR visual acuity of all eyes was 0.10 (-0.12 to 1.18). Fundus examination often revealed hyperpigmented macular spots (34 of 64 eyes [53%]) with interspersed pale-yellow deposits, although less commonly in eyes that exhibited retinal pigment epithelial atrophy (6 of 26 eyes [23%]; P < .001). Optical coherence tomography showed foci of retinal pigment epithelium elevation or thickening associated with hyperreflectance on near-infrared reflectance imaging. Fundus autofluorescence imaging typically revealed a symmetric, confluent pattern of hyperautofluorescent and hypoautofluorescent spots that involved the fovea in all eyes and extended to the retinal periphery in 24 eyes (36%). Longitudinal evaluation demonstrated dynamic changes in pigmentary abnormalities. CONCLUSIONS AND RELEVANCE: These findings suggest that PPS-associated maculopathy is a vision-threatening condition that can manifest in the setting of long-term exposure to the drug. Multimodal imaging posits a distinctive clinical phenotype, characterized in this cohort by dynamic alterations within the retinal pigment epithelium and at the retinal pigment epithelium-photoreceptor interface. Ongoing work might explore causality and direct screening guidelines.

18.
Ophthalmology ; 126(9): 1263-1270, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30419297

RESUMO

PURPOSE: To describe presenting clinical features and surgical techniques that are associated with successful surgical repair of pediatric rhegmatogenous retinal detachment (RRD). DESIGN: Retrospective interventional case series. PARTICIPANTS: Two hundred twelve eyes of 191 patients 0 to 18 years of age undergoing surgical repair for RRD between 2001 and 2015 with a minimum follow-up of 3 months. METHODS: Patients were divided into 3 age groups (0-6 years, 7-12 years, and 13-18 years) and comparisons were made using bivariate and multivariate generalized estimating equation models. A mixed means model was used to examine visual acuity in each age group over time. MAIN OUTCOME MEASURES: Complete reattachment of the retina at final follow-up. RESULTS: Of 212 eyes, 166 (78%) achieved total reattachment at final follow-up. Mean follow-up was 36.3 months. Rhegmatogenous retinal detachment associated with Stickler syndrome was more likely to occur in the younger cohorts (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.22-0.91), whereas RRD associated with blunt trauma was more likely to occur in the oldest cohort (OR, 2.3; 95% CI, 1.2-4.4). Subtotal RRD was more likely to be repaired successfully than total RRD (OR, 3.6; 95% CI, 1.5-8.4; P = 0.0100), and eyes with previous vitreoretinal surgery were less likely to undergo successful repair (OR, 0.30; 95% CI, 0.12-0.78; P = 0.0258). There was no significant difference between age groups in the rate of surgical success (P = 0.55). There was a significantly higher success rate with primary scleral buckle (SB; 63%; OR, 2.2; 95% CI, 1.1-4.5) and combined SB plus pars plana vitrectomy (PPV; 68%; OR, 2.3; 95% CI, 1.1-5.1) compared with PPV alone (51%). CONCLUSIONS: Most pediatric patients with RRD achieved complete reattachment with surgery. Success was more common in patients with a subtotal RRD at presentation. Previous vitreoretinal surgery was a risk factor for failure. Younger patients were more likely to demonstrate RRD involving the macula, but there was no difference between age groups in successful reattachment at final follow-up. Primary PPV showed a lower rate of success than SB or combined SB plus PPV.


Assuntos
Retina/fisiologia , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/cirurgia , Recurvamento da Esclera/métodos , Acuidade Visual/fisiologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Descolamento Retiniano/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento , Vitrectomia/métodos , Cirurgia Vitreorretiniana
20.
Ophthalmol Retina ; 2(4): 268-275, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-31047235

RESUMO

PURPOSE: To evaluate postoperative pain level using a supplemental peribulbar injection at the conclusion of retinal surgery. DESIGN: Prospective, parallel-assigned, single-masked, randomized clinical trial. PARTICIPANTS: Fifty-eight patients undergoing scleral buckle, vitrectomy, or combined surgery. METHODS: In a single academic institutional practice, 58 patients undergoing scleral buckle, vitrectomy, or combined surgery were enrolled. Exclusion criteria included those with a risk for glaucoma, a pre-existing chronic pain disorder, among others. Patients were assigned randomly to receive a postoperative peribulbar formulation of either bupivacaine, triamcinolone acetonide, and cefazolin (group A) or bupivacaine, balanced salt solution, and cefazolin (group B). The postoperative pain score and ocular motility were assessed by a masked observer on the first postoperative day. MAIN OUTCOME MEASURES: The primary outcome measure was the postoperative pain score. Secondary outcome measures included oral analgesic use, ocular motility, and intraocular pressure (IOP). RESULTS: The mean pain scores were 2.8±2.9 for group A and 3.8±2.6 for group B (P = 0.095). Pain was absent in 28% of group A patients versus 14% of group B patients (P = 0.11). Group A required less narcotic pain medication (hydroxycodone: group A, 0.7±3 mg vs. group B, 3±6 mg; P = 0.05; oxycodone: group A, 7±7 mg vs. 9±13 mg; P = 0.2) than group B. Motility was full in group B and limited in group A (P ≤ 0.001), with no differences in mean IOP measurements at any point after surgery. CONCLUSIONS: We did not demonstrate a statistically significant reduction in mean postoperative pain scores. However, patients in group A required less hydroxycodone use and had greater akinesia, suggesting prolonged neural blockade.

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