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PURPOSE OF REVIEW: In recent years, the field of aesthetic medicine has witnessed a paradigm shift with an increasing demand for minimally invasive cosmetic procedures, including cosmetic injectables. This review aims to delineate the distinctive role played by oculoplastic surgeons in the administration of cosmetic injectables, comparing their expertise to that of nonphysician practitioners. RECENT FINDINGS: Complications arising from cosmetic injections are discussed, including skin discoloration, inflammation, necrosis, vision loss, retinal pathology, and central nervous system adverse effects. Injector expertise, patient factors, type of filler, location of injection, and management strategies are reviewed. Findings highlight diverse practitioner involvement, common adverse effects like skin necrosis and vision loss, with hyaluronic acid fillers being prominent. Areas at the highest risk for ocular complication include the glabella and nose with potential management involving dissolving fillers and reducing pressure. Emphasis is placed on expert injector selection and patient awareness. SUMMARY: The administration of cosmetic injectables requires a profound understanding of facial anatomy, vasculature, and potential complications. In contrast to nonphysician practitioners, oculoplastic and aesthetic surgeons bring a level of anatomical precision and clinical acumen that is essential for navigating the complexities of cosmetic injectables. Emphasis on training and collaboration among practitioners will be essential in advancing the field while prioritizing patient safety and satisfaction.
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Técnicas Cosméticas , Preenchedores Dérmicos , Humanos , Técnicas Cosméticas/efeitos adversos , Preenchedores Dérmicos/efeitos adversos , Preenchedores Dérmicos/administração & dosagem , Procedimentos Cirúrgicos Minimamente Invasivos , Injeções , Papel do Médico , Cirurgiões , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversosRESUMO
PURPOSE: The initial management of patients presenting with orbital inflammatory syndromes varies-with some pursuing a diagnostic workup while others treat without any testing. The evidence behind this rationale is limited. A review of patients with orbital inflammation is performed with an analysis of diagnostic testing to develop a workflow for such patients. DESIGN: A retrospective review of patients presenting with acute orbital inflammation at a single institution from 2011 to 2020 was conducted. METHODS: Orbital imaging was required for inclusion. Patients with high suspicion of neoplasm, bacterial infection, vascular malformation, or thyroid eye disease were excluded. A review of presenting clinical findings, laboratory workup, orbital imaging, and biopsy were performed. Statistical analysis was performed identifying statistically significant diagnostic and treatment maneuvers. RESULTS: In total, 172 patients met inclusion criteria (66% female, mean age 46 years). The primary clinical presentation was myositis, dacryoadenitis, and infiltrative in 67, 73, and 32 patients (39.0%, 43.0%, 18.6%, respectively). Laboratory studies were conducted in 145 (84%) while biopsy was performed in 55 (32%). Specific orbital inflammation (SOI) was diagnosed in 29 (16.9%) with the most frequent diagnoses being sarcoidosis, IgG4-related disease, inflammatory bowel disease, and systemic lupus erythematosus. The majority (147, 85.5%) was initially treated with steroids, but steroid-sparing agent use was statistically higher in patients with SOI. CONCLUSIONS: In patients presenting with orbital inflammatory syndromes, distinguishing myositis, dacryoadenitis, and infiltrative disease has workup and differential diagnosis impacts. Because SOI is relatively common, sequelae of SOI, and potential steroid-sparing therapy needs, diagnosis via an evidence-based systemic approach is critical. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
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PURPOSE: The current study queries the American Academy of Ophthalmology (AAO) Intelligent Research in Sight (IRIS) registry for data on the epidemiology, work-up, and management patterns of autoimmune orbital inflammation. METHODS: Analysis and description of patient data from the IRIS registry between 2013 and 2019 reviewing patients with autoimmune or idiopathic orbital inflammation with filters based on International Classification of Disease (ICD) and Current Procedural Terminology (CPT) codes. Patients with thyroid eye disease, orbital cellulitis, and orbital abscess were excluded. MAIN OUTCOME MEASURES: Demographic descriptions included gender, age, geographic region, and treatment. Sub-analysis was performed by assessing rates of imaging, biopsy, lab work-up, and diagnostic categories. RESULTS: In a final cohort of 20,584 patients, the mean age of onset of orbital inflammation was 51.7 years; 67% female; and 63% Caucasian, 21% unknown, 12% Black, 2.6% Asian, and 1.5% other. Only 49 had imaging, 78 had laboratory work-up, and 1,411 had biopsy codes. Treatment results showed 166 patients receiving antibiotics, 224 patients receiving steroids, and 35 patients receiving both. CONCLUSIONS: This study assessed the epidemiology, diagnostic patterns, and treatment patterns for orbital inflammation through the AAO IRIS registry. Practise patterns suggest a relatively low overall rate of imaging and laboratory studies compared to biopsies, although this certainly under-represents the actual number of imaging and laboratory studies and exemplifies the inherent imprecision of using a large database. However, the methodology of this study provides a framework of approaching the IRIS registry for oculoplastic research.
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OBJECTIVE: Giant cell arteritis (GCA) is an age-related vasculitis. Prior studies have identified an association between GCA and hematologic malignancies (HMs). How the presence of somatic mutations that drive the development of HMs, or clonal hematopoiesis (CH), may influence clinical outcomes in GCA is not well understood. METHODS: To examine an association between CH and GCA, we analyzed sequenced exomes of 470,960 UK Biobank (UKB) participants for the presence of CH and used multivariable Cox regression. To examine the clinical phenotype of GCA in patients with and without somatic mutations across the spectrum of CH to HM, we performed targeted sequencing of blood samples and electronic health record review on 114 patients with GCA seen at our institution. We then examined associations between specific clonal mutations and GCA disease manifestations. RESULTS: UKB participants with CH had a 1.48-fold increased risk of incident GCA compared to UKB participants without CH. GCA risk was highest among individuals with cytopenia (hazard ratio [HR] 2.98, P = 0.00178) and with TET2 mutation (HR 2.02, P = 0.00116). Mutations were detected in 27.2% of our institutional GCA cohort, three of whom had HM at GCA diagnosis. TET2 mutations were associated with vision loss in patients with GCA (odds ratio 4.33, P = 0.047). CONCLUSIONS: CH increases risk for development of GCA in a genotype-specific manner, with the greatest risk being conferred by the presence of mutations in TET2. Somatic TET2 mutations likewise increase the risk of GCA-associated vision loss. Integration of somatic genetic testing in GCA diagnostics may be warranted in the future.
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Dioxigenases , Arterite de Células Gigantes , Humanos , Arterite de Células Gigantes/complicações , Mutação , Proteínas de Ligação a DNA/genéticaRESUMO
PURPOSE: To evaluate the perceived age of patients before and after functional upper blepharoplasty. METHODS: Retrospective chart review of patients who underwent upper blepharoplasty by a single surgeon at an academic center. The inclusion criterion was having external photographs before and after blepharoplasty. Exclusion criteria included any other concurrent eyelid or facial surgery. Primary endpoint: perceived change in age after surgery as judged by the American Society of Ophthalmic Plastic & Reconstructive Surgery (ASOPRS) surgeons. RESULTS: Sixty-seven patients (14 men, 53 women) were included. Mean pre-operative age was 66.9 years (range 37.8-89.4) and mean post-operative age was 67.4 years (range 38.6-89). The mean perceived age pre-operatively was 68.9 years, and the mean perceived age post-operatively was 67.1 years, a change of 1.8 years (p = 0.0001 by two-tailed paired T-test). Inter-rater reliability of the observers was measured by intraclass correlation coefficient of 0.77 for pre-operative and 0.75 for post-operative photos. The decreased perceived age was 1.9 years for women, 1.4 years for men, 0.3 years for Asians, 1.2 years for Hispanics, and 2.1 years for whites. DISCUSSION: Functional upper blepharoplasty by an experienced ASOPRS surgeon was shown to reduce the perceived age of a patient by an average of 1.8 years.
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Blefaroplastia , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Lactente , Estudos Retrospectivos , Reprodutibilidade dos Testes , Pálpebras/cirurgia , Face/cirurgiaRESUMO
Ocular leishmaniasis, a rare form of vector-borne parasitic infection, can affect the adnexa, retina, uvea, and cornea. Coinfection with human immunodeficiency virus (HIV) and Leishmania may be a distinct clinical entity as the pathogens act synergistically, enhancing each other's pathogenicity, and leading to more severe forms of the disease. Ocular leishmaniasis in the setting of HIV coinfection most commonly causes anterior granulomatous uveitis, for which the etiology can be either active ocular infection or posttreatment inflammatory phenomenon. Keratitis is not considered to be associated with HIV but has rarely been seen from direct parasite invasion or in association with miltefosine. The judicious use of steroids in the treatment of ocular leishmaniasis is critical as steroid use is paramount to the treatment of uveitis associated with posttreatment inflammatory phenomenon but can worsen the prognosis when given in the setting of active, untreated infection. Here, we present a case of unilateral keratouveitis in a leishmaniasis and HIV-coinfected male following completion of systemic antileishmanial therapy. The keratouveitis completely resolved with only the addition of topical steroids. The rapid resolution with steroids suggests that keratitis, not only uveitis, can be an immune-mediated phenomenon in post- or ongoing-treatment individuals.
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A 77-year-old Asian female with a history of left orbit exenteration and lid-sparing reconstruction for recurrent sebaceous carcinoma presented with fluid-like sensation of the left orbit. Magnetic resonance imaging (MRI) demonstrated bright T2 signal and a cyst-like cavity within the exenterated orbit. Decision was made to proceed with surgical exploration and excision. A calcified, bone-like cavity was encountered intraoperatively and removed. Histopathology revealed dense fibrous connective tissue with areas of calcification without osseous metaplasia, suggestive of retained blood in the orbit that underwent dystrophic calcification. This case report illustrates a rare occurrence of a bone-like calcific cyst following exenteration.
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Multiple reporting guidelines for artificial intelligence (AI) models in healthcare recommend that models be audited for reliability and fairness. However, there is a gap of operational guidance for performing reliability and fairness audits in practice. Following guideline recommendations, we conducted a reliability audit of two models based on model performance and calibration as well as a fairness audit based on summary statistics, subgroup performance and subgroup calibration. We assessed the Epic End-of-Life (EOL) Index model and an internally developed Stanford Hospital Medicine (HM) Advance Care Planning (ACP) model in 3 practice settings: Primary Care, Inpatient Oncology and Hospital Medicine, using clinicians' answers to the surprise question ("Would you be surprised if [patient X] passed away in [Y years]?") as a surrogate outcome. For performance, the models had positive predictive value (PPV) at or above 0.76 in all settings. In Hospital Medicine and Inpatient Oncology, the Stanford HM ACP model had higher sensitivity (0.69, 0.89 respectively) than the EOL model (0.20, 0.27), and better calibration (O/E 1.5, 1.7) than the EOL model (O/E 2.5, 3.0). The Epic EOL model flagged fewer patients (11%, 21% respectively) than the Stanford HM ACP model (38%, 75%). There were no differences in performance and calibration by sex. Both models had lower sensitivity in Hispanic/Latino male patients with Race listed as "Other." 10 clinicians were surveyed after a presentation summarizing the audit. 10/10 reported that summary statistics, overall performance, and subgroup performance would affect their decision to use the model to guide care; 9/10 said the same for overall and subgroup calibration. The most commonly identified barriers for routinely conducting such reliability and fairness audits were poor demographic data quality and lack of data access. This audit required 115 person-hours across 8-10 months. Our recommendations for performing reliability and fairness audits include verifying data validity, analyzing model performance on intersectional subgroups, and collecting clinician-patient linkages as necessary for label generation by clinicians. Those responsible for AI models should require such audits before model deployment and mediate between model auditors and impacted stakeholders.
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Suction aspiration, which has not yet been described in the treatment for myiasis in the periorbital and facial regions, was used to achieve rapid resolution of maggot burden in a 78-year-old patient who presented with a large ulcerated squamous cell carcinoma of the face. This technique also facilitates submission of parasite samples for further analysis. Suction aspiration had no complications, such as significant residual ruptured maggots in the wound or eye injury. Suction aspiration is a safe and efficient technique to reduce maggot burden that has advantages over classic myiasis treatments, especially near the eyes and airway.
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Carcinoma de Células Escamosas , Miíase , Idoso , Animais , Face , Humanos , Larva , Miíase/diagnóstico , Miíase/terapiaRESUMO
Purpose: To provide outcome data for transantral orbital decompression for functional and aesthetic rehabilitation for exophthalmos in stable thyroid eye disease (TED).Methods: Retrospective, non-comparative chart review of consecutive TED patients who underwent primary-graded transantral orbital decompression for exophthalmos by a single surgeon (MAB) between 2005 and 2018. Additional inclusion criteria included follow-up >90 days and no prior orbital surgery. Outcome data collection included millimeters of proptosis reduction, postoperative complications, and patient satisfaction.Results: A total 30 patients (47 orbits) were included. Average reduction in proptosis: 2.8 mm (range 0-9 mm, median 2.5 mm). Post-operatively, new onset diplopia occurred in four patients, V2 numbness in 15 patients (17 orbits), and sinusitis in 2 patients (2 orbits). Phone surveys reached 9/30 patients (14 orbits): cosmetic improvement was reported in 14/14 orbits, relief of orbital ache reported in 10/10 orbits with pre-operative ache, relief of dry eye in 8/13 orbits with preoperative dry eye, and overall satisfaction score: 8.9/10 (range 4-10, median 10).Conclusions: Graded transantral orbital decompression is a viable option for stable TED patients with orbital ache, exophthalmos, and exposure keratopathy, resulting in a high degree of functional and cosmetic satisfaction in our cohort.
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Exoftalmia , Oftalmopatia de Graves , Descompressão Cirúrgica , Exoftalmia/cirurgia , Oftalmopatia de Graves/cirurgia , Humanos , Órbita/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Hyaluronic acid (HA) fillers can be reversed with hyaluronidase, but their dose responses are not well-characterized. We evaluated 12 fillers' in vitro responses to varying doses of recombinant human hyaluronidase (RHH). METHODS: For the 12 HA gels, 0.2â¯mL aliquots were placed on six slides. Samples received no injection, saline injection, or RHH (2.5, 5, 10, or 20 units). The most resistant gels received 40 units of RHH on a seventh slide. Photos of gels were taken from bird's-eye and lateral views with a ruler at multiple time points. RESULTS: Restylane-L and Restylane Lyft were the most easily dissolvable HA fillers. Both demonstrated a significant response to 2.5 units RHH/0.2â¯mL. Juvéderm Ultra, Belotero, Restylane Silk, and Restylane Defyne had moderate resistance to RHH. Restylane Refyne, Juvéderm Ultra Plus, Vollure, Versa, and Voluma were most resistant, requiring more than 20 units RHH/0.2â¯mL for complete dissolution. Volbella was moderately resistant up to 20 units RHH but demonstrated pronounced dissolution with 40 units RHH. CONCLUSIONS: This study visually and objectively demonstrates the in vitro response of HA to dissolution by hyaluronidase. Fillers were categorized into least, moderate, and most resistant to RHH. Interesting findings include markedly different degrees of liquefaction for products used for similar indications (such as Restylane Lyft being more liquefied than Voluma), and Belotero easily flattening but retaining texture. Combined with in vivo data, this may help calculate hyaluronidase doses needed for controlled, partial reversal of commercially available HA gels.
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Técnicas Cosméticas , Preenchedores Dérmicos/administração & dosagem , Ácido Hialurônico/administração & dosagem , Hialuronoglucosaminidase/administração & dosagem , Preenchedores Dérmicos/química , Relação Dose-Resposta a Droga , Géis , Ácido Hialurônico/química , Hialuronoglucosaminidase/química , Técnicas In VitroRESUMO
Background The circulating level of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) is a valuable biomarker of acute myocardial infarction (AMI). The most electronegative low-density lipoprotein, L5, signals through LOX-1 to trigger atherogenesis. We examined the characteristics of LOX-1 and the role of L5 in aspirated coronary thrombi of AMI patients. Methods and Results Intracoronary thrombi were aspirated by performing interventional thrombosuction in patients with ST-segment-elevation myocardial infarction (STEMI; n=32) or non-ST-segment-elevation myocardial infarction (n=12). LOX-1 level and the ratio of sLOX-1 to membrane-bound LOX-1 were higher in thrombi of STEMI patients than in those of non-ST-segment-elevation myocardial infarction patients. In all aspirated thrombi, LOX-1 colocalized with apoB100. When we explored the role of L5 in AMI, deconvolution microscopy showed that particles of L5 but not L1 (the least electronegative low-density lipoprotein) quickly formed aggregates prone to retention in thrombi. Treating human monocytic THP-1 cells with L5 or L1 showed that L5 induced cellular adhesion and promoted the differentiation of monocytes into macrophages in a dose-dependent manner. In a second cohort of AMI patients, the L5 percentage and plasma concentration of sLOX-1 were higher in STEMI patients (n=33) than in non-ST-segment-elevation myocardial infarction patients (n=25), and sLOX-1 level positively correlated with L5 level in AMI patients. Conclusions The level of LOX-1 and the ratio of sLOX-1 to membrane-bound LOX-1 in aspirated thrombi, as well as the circulating level of sLOX-1 were higher in STEMI patients than in non-ST-segment-elevation myocardial infarction patients. L5 may play a role in releasing a high level of sLOX-1 into the circulation of STEMI patients.
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Membrana Celular/metabolismo , Trombose Coronária/metabolismo , Infarto do Miocárdio com Supradesnível do Segmento ST/metabolismo , Receptores Depuradores Classe E/metabolismo , Apolipoproteína B-100/metabolismo , Biomarcadores/metabolismo , Diferenciação Celular , Trombose Coronária/terapia , Feminino , Humanos , Lipoproteínas LDL/análise , Lipoproteínas LDL/metabolismo , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Receptores Depuradores Classe E/sangue , Sucção , Células THP-1 , Trombectomia , Regulação para CimaRESUMO
BACKGROUND/OBJECTIVE: The success of proton beam treatment (PBT) in uveal melanoma depends in part on the accuracy of tumour localisation. This study determined if using ultrasonography (US) to measure the distance between tumour margin and tantalum ring (DTR) in PBT planning improves local treatment success when compared with using intraoperative transillumination (TI) alone. METHODS: Retrospective analysis of patients with uveal melanoma treated at one centre between January 2006 and June 2017 with ≥12-month follow-up (or until treatment failure). Local tumour control was compared among study groups based on methods for measuring DTR: Group 1 (TI alone), Group 2A (postoperative US alone) and Group 2B (combination). RESULTS: Fifty-four eyes (54 patients) with uveal melanomas were included: Group 1 (22 eyes, 41%), Group 2A (11 eyes, 20%) and Group 2B (21 eyes, 39%). Mean age at diagnosis was 64 years [median 66 years, range 23-86 years]. Fifty tumours (93%) involved the choroid, while four involved the ciliary body (7%). In Group 2B, PBT treatment was based on the DTR obtained using US; DTR differed between TI and US by ≥1 mm for 25 rings in 16 eyes and ≥2 mm for 12 rings in 7 eyes. Five-year Kaplan-Meier estimate revealed a difference in local treatment success between Groups 1 and 2, (0.82 vs. 1.0, p = 0.02) with no difference in overall survival estimate, (0.85 vs. 0.83, p = 0.8). CONCLUSIONS: US can be used to measure DTR in PBT planning for uveal melanoma. This may improve accuracy of tumour localisation and improve local treatment success.
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Melanoma/radioterapia , Transiluminação/métodos , Ultrassonografia/métodos , Úvea/diagnóstico por imagem , Neoplasias Uveais/radioterapia , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Terapia com Prótons/métodos , Estudos Retrospectivos , Resultado do Tratamento , Úvea/efeitos da radiação , Neoplasias Uveais/diagnóstico , Adulto JovemRESUMO
BACKGROUND/AIMS: Enucleation for retinoblastoma is performed less often in the past decade due to increasingly widespread alternative therapies, but enucleation remains an important option. There is a paucity of reports on the current incidence of metastases and metastatic deaths in unilateral retinoblastoma from US centres. METHODS: Retrospective chart review at five tertiary retinoblastoma centres in the USA for unilateral retinoblastoma patients treated with primary enucleation, 2007-2017, with >1 year of follow-up or treatment failure. RESULTS: Among 228 patients (228 eyes), there were nine metastases (3.9%) and four deaths (1.7%). The Kaplan-Meier estimate at 5 years for metastasis-free survival was 96% (95% CI, 94% to 99 %), and for overall survival was 98% (95% CI 96% to 100%). All metastases were evident within 12 months. Histopathology revealed higher risk pathology (postlaminar optic nerve and/or massive choroidal invasion) in 62 of 228 eyes (27%). Of these higher risk eyes, 39 received adjuvant chemotherapy. There were four subsequent metastases in this higher risk pathology with adjuvant chemotherapy group, with three deaths. Of the nine overall with metastases, seven (78%) showed higher risk pathology. All metastatic patients were classified as Reese-Ellsworth V and International Classification of Retinoblastoma Groups D or E. Initial metastases presented as orbital invasion in seven of nine cases. CONCLUSIONS: Primary enucleation for unilateral retinoblastoma results in a low rate of metastatic death, but is still associated with a 3.9% chance of metastases within a year of enucleation. Most but not all patients who developed metastases had higher risk histopathological findings.
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Enucleação Ocular , Neoplasias da Retina , Retinoblastoma , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Estimativa de Kaplan-Meier , Masculino , Neoplasias da Retina/mortalidade , Neoplasias da Retina/cirurgia , Retinoblastoma/mortalidade , Retinoblastoma/cirurgia , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Dysregulation of plasma lipids is associated with age-related cardiovascular diseases. L5, the most electronegative subfraction of chromatographically resolved low-density lipoprotein (LDL), induces endothelial dysfunction, whereas the least electronegative subfraction, L1, does not. In this study, we examined the effects of L5 on endothelial senescence and its underlying mechanisms. C57B6/J mice were intravenously injected with L5 or L1 (2 mg kg-1 day-1 ) from human plasma. After 4 weeks, nuclear γH2AX deposition and senescence-associated ß-galactosidase staining indicative of DNA damage and premature senescence, respectively, were increased in the aortic endothelium of L5-treated but not L1-treated mice. Similar to that, in Syrian hamsters with elevated serum L5 levels induced by a high-fat diet, nuclear γH2AX deposition and senescence-associated ß-galactosidase staining were increased in the aortic endothelium. This phenomenon was blocked in the presence of N-acetyl-cysteine (free-radical scavenger) or caffeine (ATM blocker), as well as in lectin-like oxidized LDL receptor-1 (LOX-1) knockout mice. In cultured human aortic endothelial cells, L5 augmented mitochondrial oxygen consumption and mitochondrial free-radical production, which led to ATM activation, nuclear γH2AX deposition, Chk2 phosphorylation, and TP53 stabilization. L5 also decreased human telomerase reverse transcriptase (hTERT) protein levels and activity. Pharmacologic or genetic manipulation of the reactive oxygen species (ROS)/ATM/Chk2/TP53 pathway efficiently blocked L5-induced endothelial senescence. In conclusion, L5 may promote mitochondrial free-radical production and activate the DNA damage response to induce premature vascular endothelial senescence that leads to atherosclerosis. Novel therapeutic strategies that target L5-induced endothelial senescence may be used to prevent and treat atherosclerotic vascular disease.
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Senescência Celular/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Lipoproteínas LDL/farmacologia , Mitocôndrias/efeitos dos fármacos , Animais , Células Cultivadas , Endotélio Vascular/metabolismo , Humanos , Injeções Intravenosas , Lipoproteínas LDL/administração & dosagem , Lipoproteínas LDL/sangue , Mesocricetus , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismoRESUMO
PURPOSE: This single-dose, randomized, open-label, parallel-group, and crossover study assessed pharmacokinetics (PK), pharmacodynamics (PD), and safety of ticagrelor in subjects on hemodialysis versus healthy subjects. METHODS: Hemodialysis subjects were randomized, receiving a single ticagrelor 90-mg dose 1 day post-hemodialysis or just before hemodialysis, with an intervening washout of ≥ 7 days. Healthy subjects (creatinine clearance ≥ 90 mL/min) received a single ticagrelor 90-mg dose. PK, PD (P2Y12 reaction units [PRU], inhibition of platelet aggregation [IPA]), and safety were evaluated. RESULTS: Twenty-seven subjects (14 hemodialysis, 13 healthy) received ticagrelor. The mean maximum plasma concentration (Cmax) and area under the plasma concentration curve from time zero to infinity (AUC0-∞) of ticagrelor were 598.4 ng/mL and 3256.1 ng·h/mL, respectively, in pre-hemodialysis subjects; 560.3 ng/mL and 3015.1 ng·h/mL, respectively, in post-hemodialysis subjects; and 370.8 ng/mL and 2188.8 ng·h/mL, respectively, in healthy subjects. Cmax and AUC0-∞ of AR-C124910XX, the active metabolite, were 152.3 ng/mL and 1144.2 ng·h/mL, respectively, in pre-hemodialysis subjects; 130.8 ng/mL and 1127.8 ng·h/mL, respectively, in post-hemodialysis subjects; and 111.7 ng/mL and 1000.4 ng·h/mL, respectively, in healthy subjects. Mean IPA time curves over 24 h post-dose were almost indistinguishable for all three treatments. The greatest reduction in mean PRU occurred approximately 2 h post-dose for all three treatments. No safety or tolerability issues were identified. CONCLUSION: Hemodialysis resulted in modestly higher exposure to ticagrelor and AR-C124910XX, with no clinically significant effect on PD or tolerability. Accordingly, no dose adjustment is required for hemodialysis patients. Timing of hemodialysis has little impact on ticagrelor PK, or the effect of ticagrelor on IPA.
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Adenosina/análogos & derivados , Plaquetas/efeitos dos fármacos , Nefropatias/terapia , Rim/fisiopatologia , Inibidores da Agregação Plaquetária/farmacocinética , Antagonistas do Receptor Purinérgico P2Y/farmacocinética , Diálise Renal , Adenosina/administração & dosagem , Adenosina/sangue , Adenosina/farmacocinética , Adulto , Plaquetas/metabolismo , Estudos Cross-Over , Feminino , Humanos , Nefropatias/sangue , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/sangue , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/sangue , Receptores Purinérgicos P2Y12/sangue , Receptores Purinérgicos P2Y12/efeitos dos fármacos , Ticagrelor , Estados UnidosRESUMO
INTRODUCTION: Our aim was to compare the effect of techniques of wound closure in the emergent colon surgery with wound class IV. METHODS: Using 2014 the colectomy targeted ACS-NSQIP dataset; we identified patients undergoing emergent colectomy with wound class IV. Comparison of surgical incision complete closure versus leaving the skin open and multivariate logistic regression analyses was performed. RESULTS: Of 1792 patients undergoing emergent colectomy with wound class IV, the complete closure cohort had 1376 patients and the incision skin open cohort had 416 patients. The incidence of deep SSI was 2.3% in the complete closure cohort vs. 1.2% in the incision skin open, p = 0.15, and intra-abdominal abscess rate was 11.8% in the complete closure cohort vs. 12.3% in the incision skin open, p = 0.78. The dehiscence rate, readmission rate, and reoperation rates were not statistically significant between two cohorts. A multivariate model for dehiscence did not yield significant association between the complete closure cohort and incision skin open cohort. CONCLUSIONS: Surgical incision complete wound closure in the emergent colon surgery with wound class III/IV is safe and effective.
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Colectomia/efeitos adversos , Colo/cirurgia , Emergências , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/cirurgia , Ferida Cirúrgica/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Reoperação , Estudos Retrospectivos , Fatores de Risco , Ferida Cirúrgica/diagnóstico , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The development of immune checkpoint inhibitors has revolutionized the treatment of cancer. Their use in non-small cell lung cancer (NSCLC) remains in its infancy, but rapid progress has been made in treating metastatic NSCLC. METHODS: This article outlines the role of immune checkpoint inhibitors in the treatment of malignancy and reviews clinical trials of novel immunotherapies in the setting of metastatic NSCLC. RESULTS: Traditional chemotherapy with a platinum-based doublet has long been the backbone in the treatment of metastatic NSCLC. While the treatment of NSCLC can be targeted to specific mutations such as epidermal growth factor receptor, these subgroups are rare. The development of immunotherapy has expanded the treatment options for patients who have failed initial chemotherapy. Additionally, new studies have shown positive results for the use of immunotherapy in the first-line setting under certain conditions, allowing pembrolizumab to become the first immunotherapy to be approved in the first-line setting. CONCLUSION: Treatment of NSCLC is constantly changing, and new immune checkpoint inhibitors have shown promising results. Clinical trials are examining their use in the adjuvant setting and in combination with other therapies, and these combination therapies have the potential to show even greater benefits and broader applications than the individual drugs themselves.