RESUMO
OBJECTIVES: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative. METHODS: vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi-square test were used to calculate their associations with certain trial characteristics. RESULTS: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. CONCLUSION: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO-FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real-world.
Assuntos
Neoplasias Encefálicas , Carcinoma de Células Renais , Infecções por HIV , Hepatite C , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Hepatite C/tratamento farmacológico , Neoplasias Renais/tratamento farmacológicoRESUMO
BACKGROUND: Preclinical evidence demonstrating circadian rhythmicity within the immune system provides a rationale for hypothesis that immune checkpoint inhibitor (ICI) infusion time-of-day may serve as an actionable mechanism to improve outcomes. Herein, we explore the association between ICI time of infusion (TOI) and outcomes in metastatic renal cell carcinoma (mRCC). METHODS: Data from patients with mRCC who received nivolumab or nivolumab/ipilimumab, in first- or second-line were retrospectively collected. Patients who received < 20% of infusions after 16:30 were assigned to the early TOI sub-cohort, while the rest were assigned to the late TOI sub-cohort. Clinical outcomes were compared across the 2 groups. RESULTS: Among 135 patients included, 89 (65.9%) and 46 (34.1%) were assigned to early and late TOI sub-cohorts, respectively. Baseline characteristics were comparable across the 2 sub-cohorts. Objective response rate (ORR) was 36.0% with early TOI versus 29.5% with late TOI (P = .157). Median time to treatment failure (TTF) was 9.5 months in the early TOI sub-cohort versus 4.6 months in the late TOI sub-cohort with a hazard ratio (HR) of 1.405 (95% CI, 0.919-2.149; P = .11) in univariate analysis and 1.694 (95% CI, 1.064-2.698; P = .026) in multivariate analysis. Higher cut offs allocating patients into the late TOI sub-cohort yielded an incremental increase in the HR for TTF and overall survival (OS) that reached statistical significance. CONCLUSIONS: In patients with mRCC, early TOI yielded a numerical increase in ORR, TTF and OS, with the TTF difference reaching significance in multivariate analysis. Prospective randomized studies are warranted to examine the impact of chronomodulation on outcomes with ICIs in mRCC.
Assuntos
Antineoplásicos Imunológicos , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Nivolumabe/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/patologia , Estudos Retrospectivos , Estudos Prospectivos , Antineoplásicos Imunológicos/uso terapêuticoRESUMO
PURPOSE: Eligibility criteria illustrate the characteristics of the study population and promote the safety of participants. However, overreliance on restrictive eligibility criteria may limit the generalizability of outcomes. As a result, the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) issued statements to curtail these challenges. In this study, we aimed to assess restrictiveness in eligibility criteria across advanced prostate cancer clinical trials. MATERIALS AND METHODS: We identified all phase I, II, and III advanced prostate cancer clinical trials between June 30, 2012, and June 30, 2022, through Clinicaltrials.gov. We evaluated whether a clinical trial excluded, conditionally included, or did not report 4 common criteria: brain metastases, prior or concurrent malignancies, HIV infection, and hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. Performance status (PS) criteria were recorded based on the Eastern Cooperative Oncology Group (ECOG) scale. RESULTS: Out of 699 clinical trials within our search strategy, 265 (37.9%) trials possessed all the required data and were included in our analysis. The most common excluded condition of our interest was brain metastases (60.8%), followed by HIV positivity (46.4%), HBV/HCV positivity (46.0%), and concurrent malignancies (15.5%). Additionally, 50.9% of clinical trials only included patients with ECOG PS 0 to 1. HIV and HBV/HCV infection were exclusion criteria of 22 (80.8%) and 19 (73.1%) immunotherapy trials, respectively. CONCLUSION: Patients with brain metastases, prior or concurrent malignancies, HIV infection, HBV/HCV infection, or low-functioning PS were overly restricted from participating in advanced prostate clinical trials. Advocating for broader criteria may ameliorate generalizability.
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Neoplasias Encefálicas , Infecções por HIV , Hepatite C , Neoplasias da Próstata , Masculino , Humanos , Infecções por HIV/tratamento farmacológico , Amigos , Neoplasias da Próstata/terapia , OncologiaRESUMO
The introduction of targeted therapy (TT) and immuno-oncology (IO) agents have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). However, despite the significant improvements in survival and clinical response yielded by these agents, a significant percentage of patients still experience progressive disease. Evidence now suggests that microorganisms living in the gut (i.e., the gut microbiome) could be used as a biomarker for response and may also have utility in increasing response to these treatments. In this review, we present an overview of the role of the gut microbiome in cancer and its potential implications in the treatment of mRCC.
RESUMO
Stereotactic body radiation therapy (SBRT) has been shown to be safe and effective for delaying systemic treatment change among patients with metastatic renal cell carcinoma (mRCC). In this study, we sought to assess the genomic signatures of patients with mRCC who underwent SBRT for oligoprogression. A total of 30 patients with oligoprogressive disease were identified, the majority of whom had clear cell renal cell carcinoma (83.3%) and were receiving first-line treatment (53.3%). Genomic and transcriptomic sequencing were available in 20 and 16 patients, respectively. Duration of systemic treatment (DOT) was categorized as that prior (DOT[P]) and subsequent (DOT[S]) to radiation treatment. The median DOT(P) and DOT(S) were 15.1 and 18.3 mo, respectively, with a median DOT(S)/DOT(P) ratio of 1.4. Patients who had a DOT(S)/DOT(P) ratio of ≥1 had increased expression in pathways related to cell proliferation and development. In contrast, among patients with a ratio of ≤1, the reactive oxygen species pathway was enriched. This study highlights the potential role of genomics and transcriptomics to refine radiation treatment selection in patients with mRCC. PATIENT SUMMARY: In this study, we looked at mutations and genomic expressions among kidney cancer patients who responded better to stereotactic body radiotherapy. We found that enriched expression of certain pathways might play a role in response to radiotherapy.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Radiocirurgia , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/radioterapia , Radiocirurgia/efeitos adversos , Transcriptoma , GenômicaRESUMO
Since the approval of the COVID-19 vaccines, their safety and efficacy has been widely demonstrated in patients with cancer. However, there remain patients with reservations regarding vaccination. We aimed to assess genitourinary cancer patients' perceptions of the vaccines as well as barriers and influencers of decision-making through the completion of a questionnaire. While vaccine-associated concerns were observed, most patients with genitourinary cancers were willing to receive the vaccine. Moving forward, differing strategies could be considered to enhance patient education on the utility of vaccination in the setting of cancer and beyond.
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Vacinas contra COVID-19 , COVID-19 , Neoplasias Urogenitais , Humanos , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , VacinaçãoAssuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/secundário , Suplementos Nutricionais , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Resultado do TratamentoRESUMO
In an era of several therapeutic options available, optimal treatment sequencing is crucial to providing patients the most effective therapy and promoting quality of life. In clear cell renal cell carcinoma, a combination approach with an immunotherapy backbone, such as nivolumab/ipilimumab or axitinib/pembrolizumab, has a key role in the first-line setting. Safety and activity data support the transition to single-agent targeted therapies in the second-line setting. Nivolumab monotherapy possesses clinical and mechanistic rationale as a second-line therapeutic option for patients treated with targeted therapies in the first-line setting. Gene expression models are being generated from large prospective clinical trial data sets.
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Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Expressão Gênica , Humanos , Imunoterapia , Terapia de Alvo MolecularAssuntos
COVID-19/epidemiologia , Disseminação de Informação/métodos , Oftalmologia/métodos , SARS-CoV-2 , Mídias Sociais/estatística & dados numéricos , Pesquisa Biomédica , COVID-19/prevenção & controle , Transmissão de Doença Infecciosa/prevenção & controle , Humanos , Colaboração Intersetorial , Oftalmologistas/organização & administração , Padrões de Prática Médica/organização & administraçãoRESUMO
PURPOSE: To assess the outcomes of micropulse transscleral cyclophotocoagulation for intraocular pressure (IOP) control in keratoplasty eyes. METHODS: Outcomes of micropulse laser treatments of postkeratoplasty eyes were retrospectively reviewed. IOP was assessed with applanation tonometry. Keratoplasty survival was calculated with Kaplan-Meier survival analysis. RESULTS: Sixty-one eyes in 57 patients received laser treatment; 31 eyes received 1, 21 received 2, 8 received 3, and 1 received 4 treatments. The median follow-up was 21 months (range, 2-35 months). At baseline, the mean IOP was 28 ± 11 mm Hg. At 1, 3, 6, and 12 months after the last treatment, respectively, the numbers of eyes with IOP data were 58, 50, 46, and 38; the mean IOP was 17 ± 7, 17 ± 8, 18 ± 9, and 15 ± 5 mm Hg; the proportions of eyes with IOP ≤ 15 mm Hg were 40%, 51%, 48%, and 55%; and the proportions with IOP ≤ 12 mm Hg were 21%, 29%, 20% and 29%. Six eyes (10%) received subsequent glaucoma filtration surgery. The mean number of antiglaucoma medications used before the initial treatment was 2.7 (range, 0-4) versus 2.2 (range, 0-4) at last follow-up. At baseline, 7 grafts were decompensated and 5 of 54 clear grafts (9%) had endothelial cell density < 700 cells/mm. Graft survival was 94% at 1 year and 81% at 2 years after the initial laser treatment. CONCLUSIONS: Micropulse transscleral cyclophotocoagulation is a noninvasive alternative to glaucoma filtration surgery for IOP reduction in keratoplasty eyes.
Assuntos
Glaucoma/cirurgia , Ceratoplastia Penetrante , Fotocoagulação a Laser/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glaucoma/fisiopatologia , Sobrevivência de Enxerto , Humanos , Pressão Intraocular/fisiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tonometria OcularRESUMO
PURPOSE: To evaluate outcomes and graft survival of Descemet membrane endothelial keratoplasty (DMEK) for failed penetrating keratoplasty (PK). METHODS: Ninety-three DMEK procedures performed in 84 eyes of 77 patients with failed PK were retrospectively reviewed. The main outcomes were corrected distance visual acuity and graft survival assessed with Kaplan-Meier survival analysis and proportional hazards modeling taking follow-up into consideration. RESULTS: Sixty-nine eyes had 1 previous failed PK, 13 had 2, 1 had 3, and 1 had 4. Ten eyes had failed Descemet stripping endothelial keratoplasty (DSEK) performed under failed PK. Fourteen cases (15%) had previous glaucoma filtration surgery (9 trabeculectomy alone; 5 trabeculectomy and aqueous shunt). Median follow-up was 21 months (range, 1 month to 7 years). Median Snellen corrected distance visual acuity improved from 20/100 preoperatively (range, 20/30 to count fingers) to 20/30 at 6 months postoperatively (n = 73; range, 20/20-20/200). Rebubbling rates were 53% when the diameter of the DMEK graft was oversized, 27% when same sized, and 33% when undersized relative to that of the previous PK graft. Two grafts (2%) experienced an immunologic rejection episode, and 15 (16%) failed, including 5 primary/early failures and 10 late failures. Previous glaucoma surgery was the only significant risk factor for failure (relative risk, 7.1; 95% confidence interval, 2.1-37.0). The 1-, 2-, and 3-year graft survival rates were 96%, 89%, and 89% without versus 78%, 53%, and 39% with previous glaucoma surgery. CONCLUSIONS: Treatment of failed PK with DMEK produced similar 4-year survival (76%) and better visual outcomes than previously reported with Descemet stripping endothelial keratoplasty or an initial PK regraft.
Assuntos
Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Glaucoma/cirurgia , Sobrevivência de Enxerto , Adulto , Idoso , Idoso de 80 Anos ou mais , Lâmina Limitante Posterior/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/estatística & dados numéricos , Feminino , Glaucoma/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Ceratoplastia Penetrante , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To assess patient satisfaction with corneal crosslinking (CXL). SETTING: Price Vision Group, Indianapolis, Indiana, USA. DESIGN: Prospective case series. METHODS: Patients treated with the Dresden protocol or accelerated epithelium-off CXL during an 8-year period were invited to participate in an electronic survey. RESULTS: Of the 552 patients who were invited to participate, 448 (80% response rate) completed the electronic survey. The median time from CXL to survey completion was 3.5 years (range 1 to 9 years). The participants were 73% men; 78% had keratoconus, 22% had post-refractive surgical ectasia, and 44% had bilateral treatment. Comparable proportions of those treated with standard and accelerated CXL reported that it halted disease progression (88% versus 87%, respectively, P = .78). A younger treatment age was associated with higher perceived efficacy (P = .0003). The proportion who considered CXL effective was 93% among those with mild keratoconus, 86% with moderate to severe keratoconus, and 78% with post-refractive surgical ectasia (P = .0004). Regarding vision, 41% reported improvement after CXL, 46% noted no change, and 14% perceived continued decline. The mean satisfaction score was 8.8 ± 1.7 (SD) on a scale of 1 (would not recommend CXL) to 10 (definitely would recommend) among those treated for keratoconus and 7.6 ± 2.5 among those treated for ectasia after keratorefractive surgery (P < .0001). Eleven (1.7%) of 644 treated eyes had subsequent keratoplasty. CONCLUSION: Most patients considered CXL effective. The perceived efficacy did not vary significantly as a function of follow-up time (P = .90), suggesting no discernible fading of effect over the 1- to 9-year follow-up.
Assuntos
Reagentes de Ligações Cruzadas , Epitélio Corneano/cirurgia , Ceratocone/tratamento farmacológico , Satisfação do Paciente/estatística & dados numéricos , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico , Adolescente , Adulto , Idoso , Criança , Colágeno/metabolismo , Paquimetria Corneana , Substância Própria/efeitos dos fármacos , Substância Própria/metabolismo , Topografia da Córnea , Desbridamento/métodos , Feminino , Humanos , Ceratocone/metabolismo , Ceratocone/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia/métodos , Estudos Prospectivos , Resultado do Tratamento , Raios Ultravioleta , Acuidade Visual/fisiologia , Adulto JovemRESUMO
PURPOSE: To identify whether intraoperative hyphema from the peripheral iridotomy during Descemet membrane endothelial keratoplasty (DMEK) is associated with anticoagulant or antiplatelet use, age, combined phacoemulsification, or adverse outcomes. SETTING: Price Vision Group, Indianapolis, Indiana, USA. DESIGN: Retrospective case series. METHODS: Data were obtained from consecutive DMEK cases with an intraoperative iridotomy from July 2015 through July 2016. Hyphema was classified as negative or positive (small or large). Associations with possible risk factors and with transplant outcomes were assessed. RESULTS: Of 445 cases, 262 (59%) were negative for hyphema and 183 (41%) were positive. The proportion of patients who used preoperative anticoagulant or antiplatelet medication did not differ significantly with the hyphema classification (negative hyphema 42%, small hyphema 34%, large hyphema 46%) (P = .31). Likewise, recipient age was not a risk factor for hyphema (P = .085). Hyphema was more likely in cases combined with phacoemulsification than in single DMEK procedures (relative risk, 1.5 [95% confidence interval, 1.2-1.9]). Hyphema was not associated with postoperative rebubbling rates (negative hyphema 10.5%, small hyphema 10.3%, large hyphema 8.0%) (P = .33), 6-month endothelial cell loss (mean = 29%, P = .19), or 6-month visual acuity (mean = 20/25 Snellen in all hyphema groups, P = .98). CONCLUSIONS: Preoperative anticoagulant or antiplatelet use was not a significant risk factor for hyphema. The risk for hyphema was increased somewhat when DMEK was combined with cataract surgery. Intraoperative hyphema did not significantly affect the rebubbling rate, endothelial cell loss, or visual acuity outcomes.
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Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Hifema/etiologia , Complicações Intraoperatórias , Facoemulsificação/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Edema da Córnea/cirurgia , Feminino , Distrofia Endotelial de Fuchs/cirurgia , Humanos , Iridectomia , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE: To investigate whether the riboflavin dosing frequency affects corneal cross-linking efficacy or safety, given that isotonic riboflavin solution is viscous and each installation coats the corneal surface with a film that absorbs some of the incident ultraviolet A light. DESIGN: Prospective, randomized, single-center equivalence trial. PARTICIPANTS: Patients with progressive keratoconus or ectasia after refractive surgery (n = 510). METHODS: One eye per patient was prospectively randomized to 2-minute or 5-minute riboflavin dosing intervals with standard corneal cross-linking (epithelial removal and 30-minute irradiation with 3 mW/cm2 ultraviolet A light). Block randomization resulted in comparable representation of keratoconus and ectasia after refractive surgery in the 2 treatment arms. Treatment equivalence was assessed using the 2 one-sided test. Fellow eyes (n = 207) were treated with 5-minute dosing and considered in the safety analysis. MAIN OUTCOME MEASURES: The primary hypothesis was equivalent change in the topography-derived maximum keratometry value from baseline to 6 months with 2-minute vs. 5-minute dosing. A ±0.75-diopter margin of equivalence for the treatment difference between dosing regimens was considered clinically relevant. Adverse events and changes from baseline to 6 months in corrected distance visual acuity (CDVA), uncorrected distance visual acuity, and minimum corneal thickness were assessed. RESULTS: The mean reduction in maximum keratometry from baseline was equivalent with 2-minute and 5-minute riboflavin dosing intervals at 6 months (0.97 and 0.76 diopters, respectively; 90% confidence interval for treatment difference, -0.23 to 0.66; per-protocol population). With both dosing intervals, the mean improvement in CDVA was 0.07 logarithm of the minimum angle of resolution or 3.5 letters at 6 months. Of the 635 study and fellow eyes examined at 6 months, 134 (21%) gained and 32 (5%) lost 2 or more lines of CDVA. Three eyes (0.4%) developed sterile infiltrates, 1 (0.1%) had delayed epithelial healing with dendrites, and 3 (0.4%) had recurrent epithelial defects. Three eyes (0.4%) were re-treated. CONCLUSIONS: The 2 riboflavin dosing regimens produced equivalent reduction in the maximum keratometry value, with a favorable safety profile.
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Colágeno/metabolismo , Substância Própria/metabolismo , Reagentes de Ligações Cruzadas , Ceratocone/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Riboflavina/administração & dosagem , Adolescente , Adulto , Idoso , Criança , Paquimetria Corneana , Topografia da Córnea , Dilatação Patológica/tratamento farmacológico , Dilatação Patológica/metabolismo , Dilatação Patológica/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Ceratocone/metabolismo , Ceratocone/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Refração Ocular/fisiologia , Equivalência Terapêutica , Fatores de Tempo , Raios Ultravioleta , Acuidade Visual/fisiologiaRESUMO
PURPOSE: To assess the rejection episode rate after deep anterior lamellar keratoplasty (DALK) and to identify associated risk factors. METHODS: This retrospective review of 251 primary DALK procedures performed by 14 surgeons at a single center between February 2008 and November 2015 evaluated the rejection episode rate and associated risk factors using Kaplan-Meier survival and proportional hazards analyses, which took the length of follow-up into consideration. RESULTS: Transplant indications were keratoconus or ectasia after laser refractive surgery (n = 170, 68%), corneal opacity (n = 72, 28%), and other anterior corneal disease (n = 9, 4%). The median recipient age was 46 years. The overall rejection episode rate was 14% with 18-month median follow-up and a 7-week median postoperative corticosteroid duration. In univariate analysis, increased risk of rejection episodes was associated with younger recipient age [relative risk (RR): 2.1, 95% confidence interval (CI): 1.4-5.2], African American race (RR: 2.1, 95% CI: 1.1-4.1), and use of manual trephination (compared with the femtosecond laser) for the side-cut incisions (RR: 2.7, 95% CI: 1.4-5.2). In multivariate analysis, the combined effect of patient age and race (P = 0.0012) and the side-cut method (P = 0.021) were each significant risk factors. CONCLUSIONS: This study demonstrates the substantial rate of rejection episodes that can be induced by corneal stroma in DALK and suggests that postoperative topical corticosteroids should be continued longer than the study's 7-week median and that young African Americans need higher-dose, longer-duration topical corticosteroids. The association between the side-cut method and rejection risk merits further investigation.
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Doenças da Córnea/cirurgia , Rejeição de Enxerto/imunologia , Ceratoplastia Penetrante/métodos , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Dissecação/métodos , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Corneal endothelium (CE) is among the most metabolically active tissues in the body. This elevated metabolic rate helps the CE maintain corneal transparency by its ion and fluid transport properties, which when disrupted, leads to visual impairment. Here we demonstrate that glutamine catabolism (glutaminolysis) through TCA cycle generates a large fraction of the ATP needed to maintain CE function, and this glutaminolysis is severely disrupted in cells deficient in NH3:H+ cotransporter Solute Carrier Family 4 Member 11 (SLC4A11). Considering SLC4A11 mutations leads to corneal endothelial dystrophy and sensorineural deafness, our results indicate that SLC4A11-associated developmental and degenerative disorders result from altered glutamine catabolism. Overall, our results describe an important metabolic mechanism that provides CE cells with the energy required to maintain high level transport activity, reveal a direct link between glutamine metabolism and developmental and degenerative neuronal diseases, and suggest an approach for protecting the CE during ophthalmic surgeries.
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Trifosfato de Adenosina/metabolismo , Endotélio Corneano/metabolismo , Metabolismo Energético , Glutamina/metabolismo , Sistema X-AG de Transporte de Aminoácidos/genética , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular , Células Cultivadas , Ciclo do Ácido Cítrico , Distrofias Hereditárias da Córnea/genética , Distrofias Hereditárias da Córnea/metabolismo , Distrofias Hereditárias da Córnea/patologia , Epitélio Corneano/citologia , Epitélio Corneano/metabolismo , Distrofia Endotelial de Fuchs/genética , Distrofia Endotelial de Fuchs/metabolismo , Distrofia Endotelial de Fuchs/patologia , Expressão Gênica , Humanos , Transporte de Íons , Camundongos Knockout , Microscopia de Fluorescência , Mutação , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas SLC4A/genética , Proteínas SLC4A/metabolismoRESUMO
PURPOSE: To assess frequency, associations, and outcomes of full air fill after Descemet membrane endothelial keratoplasty (DMEK). METHODS: This retrospective study reviewed 368 consecutive DMEK cases performed to treat Fuchs dystrophy, bullous keratopathy, or failed keratoplasty. Primary outcomes were air bubble status, intraocular pressure, and incidence of pupil block and air reinjection. RESULTS: Using an air management algorithm, slit-lamp assessment 1 hour after DMEK identified complete air fill in 80/368 eyes (22%). This spontaneously resolved in 45 eyes. Air was removed from 35 eyes (9%). Eyes that required air removal were more likely to have occluded iridotomy than did eyes in which the full air fill spontaneously resolved (23% vs. 6.6%, respectively), P = 0.05. Although full air fill was more likely after DMEK combined with cataract surgery (P = 0.001), air removal was more likely after DMEK-only procedures (P = 0.01). Eyes that underwent air removal tended to have lower rebubble rates, although this did not reach statistical significance (P = 0.06). No cases of pupillary block glaucoma occurred, and full air fill did not significantly affect 6-month postoperative vision or endothelial cell density. CONCLUSIONS: A careful air management strategy successfully prevented pupil block in eyes that developed full air fill. DMEK-only procedures were more likely to require air removal than those combined with cataract surgery, which suggests that decreased zonular flexibility may prevent the air bubble from taking a more spherical shape and more easily allow occlusion of iridotomy.
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Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Distúrbios Pupilares/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Ar , Contagem de Células , Doenças da Córnea/cirurgia , Tamponamento Interno , Endotélio Corneano/patologia , Feminino , Glaucoma/etiologia , Glaucoma/prevenção & controle , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Distúrbios Pupilares/etiologia , Estudos Retrospectivos , Acuidade Visual/fisiologia , Adulto JovemAssuntos
Doenças da Córnea/induzido quimicamente , Endotélio Corneano/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Rejeição de Enxerto/induzido quimicamente , Memantina/efeitos adversos , Idoso de 80 Anos ou mais , Doença de Alzheimer/tratamento farmacológico , Doenças da Córnea/fisiopatologia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Endotélio Corneano/fisiopatologia , Feminino , Distrofia Endotelial de Fuchs/cirurgia , Rejeição de Enxerto/fisiopatologia , Humanos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Reoperação , Tomografia de Coerência ÓpticaRESUMO
PURPOSE: The goal of this study was to provide an update of significant corneal literature published in 2013. DESIGN: This study is a systematic literature review. METHODS: We conducted a systematic review of the English-language literature published from January 1, 2013, to December 31, 2013, using the following PubMed search and Medical Subject Headings terms: cornea transplantation, keratoplasty, Descemet membrane endothelial keratoplasty, Descemet stripping endothelial keratoplasty, cross linking, pre-Descemet's layer, Rho-associated kinase, keratoprosthesis, infectious keratitis, corneal dystrophy, corneal astigmatism, and keratoconus. RESULTS: This review summarizes relevant and innovative original articles, review articles, and novel techniques from the following journals: American Journal of Ophthalmology, British Journal of Ophthalmology, Cornea, Graefe's Archive for Clinical and Experimental Ophthalmology, Investigative Ophthalmology & Visual Science, JAMA Ophthalmology, Journal of Cataract and Refractive Surgery, Journal of Refractive Surgery, and Ophthalmology. Case reports, abstracts, letters to the Editor, and unpublished work were excluded, as well as articles e-published ahead of print in 2012 that were discussed in the previous review. One hundred twenty-seven articles met the criteria for this review. CONCLUSIONS: This review summarizes significant cornea-related literature from 2013.