Descemet's membrane endothelial keratoplasty for primary graft failure after penetrating keratoplasty / Transplante endotelial de membrana de Descemet para falência primária após transplante penetrante

ABSTRACT Primary graft failure (PGF) is a known complication following penetrating keratoplasty (PKP). The usual approach to treat this complication is to repeat a penetrating keratoplasty. Here, we report a case of Descemet's membrane endothelial keratoplasty (DMEK) for the treatment of PGF after PKP. A patient that underwent PKP, developed PGF with persistent graft edema and very poor visual acuity despite aggressive steroid use and a proof anti-viral treatment. Three months after the initial surgery, a DMEK was performed under the PKP graft. There was progressive early corneal clearing and, by the end of the first month, the patient already had no corneal edema. Uncorrected visual acuity (UCVA) improved to 20/40 and best corrected visual acuity (BCVA) to 20/20. DMEK may be an alternative to a second PKP for the treatment of PGF. This technique is a less invasive option when compared to the standard PKP procedure.

RESUMO A falência primária do enxerto é uma complicação conhecida que pode ocorrer após o transplante penetrante de córnea. O tratamento usual dessa complicação é com um novo transplante penetrante. Apresentamos um caso em que foi usado o transplante endotelial de membrana de Descemet (DMEK - do inglês Descemet membrane endo-thelial keratoplasty) para o tratamento da falência primária após o transplante penetrante. Uma paciente submetida a transplante penetrante evoluiu com falência primária do enxerto a despeito do uso intenso de corticoide tópico e uma prova terapêutica de antivirais. Três meses após a cirurgia inicial, foi optado pela realização do transplante endotelial de membrana de Descemet sob o transplante penetrante. Houve um clareamento precoce e progressivo do enxerto com melhora importante da visão. Após um mês, a visão sem correção era de 20/40 melhorando para 20/20 com refração. O transplante endotelial de membrana de Descemet pode ser uma alternativa a um novo transplante penetrante como tratamento da falência primária.

The Role of Interferon Receptors α/ß/γ Ablation During Western Diet-Induced Obesity and Insulin Resistance in the Inflectional Model AG129 Mice Strain.

Diet-induced obesity triggers elevation of circulating pro-inflammatory cytokines and acute-phase proteins, including interferons (IFNs). IFNs strongly contribute to low-grade inflammation associated with obesity-related complications, such as nonalcoholic fat liver disease and diabetes. In this study, AG129 mice model (double-knockout strain for IFN α/ß/γ receptors) was fed with a high-fat high-sucrose (HFHS) diet (Western diet) for 20 weeks aiming to understand the impact of IFN receptor ablation on diet-induced obesity, insulin resistance, and nonalcoholic fat liver disease. Mice were responsive to the diet, becoming obese after 20 weeks of HFHS diet which was accompanied by 2-fold increase of white adipose tissues. Moreover, animals developed glucose and insulin intolerance, as well as dysregulation of insulin signaling mediators such as Insulin Receptor Substrate 1 (IRS1), protein kinase B (AKT), and S6 ribosomal protein. Liver increased interstitial cells, and lipid accumulation was also found, presenting augmented fibrotic markers (transforming growth factor beta 1 [Tgfb1], Keratin 18 [Krt18], Vimentin [Vim]), yet lower expression on IFN receptor downstream proteins (Toll-like receptor [TLR] 4, nuclear factor kappa-light-chain-enhancer of activated B cells [NFκB], and cAMP response element-binding protein [CREB]). Thus, IFN receptor ablation promoted effects on NFκB and CREB pathways, with no positive effects on systemic homeostasis in diet-induced obese mice. Therefore, we conclude that IFN receptor signaling is not essential for promoting the complications of diet-induced obesity and thus cannot be correlated with metabolic diseases in a noninfectious condition.

Once a week consumption of Western diet over twelve weeks promotes sustained insulin resistance and non-alcoholic fat liver disease in C57BL/6 J mice.

The Western diet (high in fat and sucrose) consumption is a highly prevalent feature in the whole world, mainly due to the increasing consumption of ultra-processed foods (UPF), which are cheaper and easier-to-eat, as compared to fresh and highly nutritive meals. Epidemiological studies have associated UPF consumption with development of obesity, non-alcoholic fat liver disease (NAFLD) and insulin resistance. For molecular studies, mice fed with Western diets have been used to characterize signaling pathways involved in these diet-induced pathologies. However, these studies fed mice continuously with the diets, which is not compatible with what occurs in real life, when consumption is occasional. Here, we fed mice once-a-week with a high fat, high sucrose (HFHS) diet and compared these animals with those fed continuously with HFHS diet or with a standard diet. Our results show that after a single day of consuming HFHS, animals presented impaired oral glucose tolerance test (oGTT) as compared to control group. Although this impairment was reversed after 24 h consuming regular diet, repetition of HFHS consumption once-a-week aggravated the picture such as after 12-weeks, oGTT impairment was not reversed after 6 days under control diet. Liver steatosis, inflammation, impaired insulin signaling pathway and endoplasmic reticulum stress are similar comparing animals that consumed HFHS once-a-week with those that continuously consumed HFHS, though weekly-fed animals did not gain as much weight. Therefore, we conclude that regimen of one day HFHS plus 6 days normal diet over 12 weeks is sufficient to induce insulin resistance and NAFLD in mice.

P2Y2-P2X7 receptors cross-talk in primed mesenteric endothelial cells upregulates NF-κB signaling favoring mononuclear cell adhesion in schistosomiasis.

Schistosomiasis is an intravascular infectious disease that impacts over 200 million people globally. In its chronic stage, it leads to mesenteric inflammation with significant involvement of monocytes/macrophages. Endothelial cells lining the vessel lumens play a crucial role, and mount of evidence links this disease to a downregulation of endoprotective cell signaling favoring a primed and proinflammatory endothelial cell phenotype and therefore the loss of immunovascular homeostasis. One hallmark of infectious and inflammatory conditions is the release of nucleotides into the extracellular milieu, which, in turn, act as innate messengers, activating purinergic receptors and triggering cell-to-cell communication. ATP influences the progression of various diseases through P2X and P2Y purinergic receptor subtypes. Among these receptors, P2Y2 (P2Y2R) and P2X7 (P2X7R) receptors stand out, known for their roles in inflammation. However, their specific role in schistosomiasis has remained largely unexplored. Therefore, we hypothesized that endothelial P2Y2R and P2X7R could contribute to monocyte adhesion to mesenteric endothelial cells in schistosomiasis. Using a preclinical murine model of schistosomiasis associated with endothelial dysfunction and age-matched control mice, we showed that endothelial P2Y2R and P2X7R activation increased monocyte adhesion to cultured primary endothelial cells in both groups. However, a distinct upregulation of endothelial P2Y2R-driven canonical Ca2+ signaling was observed in the infected group, amplifying adhesion. In the control group, the coactivation of endothelial P2Y2R and P2X7R did not alter the maximal monocyte adhesion induced by each receptor individually. However, in the infected group, this coactivation induced a distinct upregulation of P2Y2R-P2X7R-driven canonical signaling, IL-1ß release, and VCAM-1 expression, with underlying mechanisms involving inflammasome and NF-κB signaling. Therefore, current data suggest that schistosomiasis alters endothelial cell P2Y2R/P2X7R signaling during inflammation. These discoveries advance our understanding of schistosomiasis. This intricate interplay, driven by PAMP-triggered endothelial P2Y2R/P2X7R cross-talk, emerges as a potential key player in the mesenteric inflammation during schistosomiasis.

Descemet's membrane endothelial keratoplasty for primary graft failure after penetrating keratoplasty.

Primary graft failure (PGF) is a known complication following penetrating keratoplasty (PKP). The usual approach to treat this complication is to repeat a penetrating keratoplasty. Here, we report a case of Descemet's membrane endothelial keratoplasty (DMEK) for the treatment of PGF after PKP. A patient that underwent PKP, developed PGF with persistent graft edema and very poor visual acuity despite aggressive steroid use and a proof anti-viral treatment. Three months after the initial surgery, a DMEK was performed under the PKP graft. There was progressive early corneal clearing and, by the end of the first month, the patient already had no corneal edema. Uncorrected visual acuity (UCVA) improved to 20/40 and best corrected visual acuity (BCVA) to 20/20. DMEK may be an alternative to a second PKP for the treatment of PGF. This technique is a less invasive option when compared to the standard PKP procedure.

Descolamento seroso da retina neurossensorial associado à mácula dome-shaped: relato de dois casos / Serous detachment of the sensorineural retina associated with the dome-shaped macula: report of two cases

RESUMO A mácula dome-shaped consiste na elevação convexa da região macular, encontrada principalmente em pacientes com alta miopia. O significado clínico e a correlação com outras patologias oculares ainda são incertos. Este artigo tem como objetivo descrever dois casos de mácula dome-shaped com acúmulo de fluido sub-retiniano em olhos alto míopes. Trata-se de pacientes com baixa acuidade visual, fundus miopicos e nítida elevação em forma de cúpula na área macular vista na tomografia de coerência óptica. A mácula dome-shaped pode cursar com descolamento seroso da retina neurossensorial envolvendo a fóvea, levando à baixa acuidade visual. Sua patogênese ainda não é bem estabelecida. De acordo com a tomografia de coerência óptica, a mácula dome-shaped pode ser classificada em três tipos morfológicos, sendo, nesses dois casos, demonstrada a disposição oval horizontalizada. Interessante ressaltar que o diagnóstico de mácula dome-shaped deve ser considerado em pacientes alto míopes, especialmente quando há queixa de baixa acuidade visual, que pode estar relacionada à presença de fluido sub-retiniano. Como o exame clínico não permite o diagnóstico adequado da mácula em cúpula, a realização da tomografia de coerência óptica com cortes verticais e horizontais é fundamental na suspeita de mácula dome-shaped.

ABSTRACT Dome-shaped macula consists of the convex elevation of the macular region, found mainly in patients with high myopia. The clinical significance and the correlation with other ocular pathologies are still uncertain. This article aims to describe two cases of dome-shaped macula with accumulation of subretinal fluid in high myopic eyes. Those are patients with low visual acuity, myopic fundus and a clear dome-shaped elevation in the macular area at optical coherence tomography. A dome-shaped macula can course with a serous detachment of the sensorineural retina involving the fovea, leading to low visual acuity. Such a pathogenesis is still not well studied. According to the optical coherence tomography, dome-shaped macula can be classified into three morphological types, those two cases being shown in a horizontal, oval arrangement. It is interesting to note that the diagnosis of dome-shaped macula should be considered in patients with high myopia, especially when there is a complaint of low visual acuity, which may be related to the presence of subretinal fluid in cases of dome-shaped macula. As the clinical examination does not allow an adequate diagnosis of the domed macula, the performance of the optical coherence tomography with vertical and horizontal cuts is fundamental in the suspicion of the dome-shaped macula.

Surgical Treatment Alone of Cerebral Aspergillosis in Immunocompetent Patient.

Aspergillosis is a disease that predominantly affects immunocompromised patients. The incidence in immunocompetents is rare, and manifestation is generally pulmonary. Few reports in the literature refer to isolated cerebral aspergillosis in individuals with no chronic comorbidities. We describe a case of a 59-year-old rural worker without previous pathologies who had a partial convulsive crisis in a subtle form, with self-limiting and nonrecurrent secondary generalization. Diagnostic investigation demonstrated a subcortical tumorlike lesion in the right precentral gyrus by nuclear magnetic resonance that allowed en bloc microsurgical resection, with histopathologic findings indicating cerebral aspergillosis. Because of the delay in obtaining the result of the biopsy due to technical difficulties with analysis, the diagnosis was delayed. The patient was clinically stable, with imaging without modifications and with negative serologic tests, so it was decided to follow the patient without antifungal therapy, which was successful. This was a case of isolated cerebral aspergillosis in an immunocompetent individual who was successfully treated by complete resection of the lesion alone, without combined antifungal therapy.