Visual outcomes of combined use of implantable collamer lens implantation and laser corneal visual correction for myopia over -18.00 diopters.

PURPOSE: This retrospective comparative case series explores visual outcomes in patients with extreme myopia receiving an implantable collamer lens (ICL) at -18.00 diopters (D), with central port, followed by bioptics via laser vision correction (LASIK or PRK) to address residual myopia or myopic astigmatism. SETTING: The study was conducted at Clínica Baviera - Aier Eye Hospital Group, Spain. DESIGN: Retrospective analysis of cases. METHODS: The study assessed uncorrected distance visual acuity, corrected distance visual acuity (CDVA), predictability, safety, efficacy, and patient satisfaction after implantation of the ICL and bioptics. The model implanted was V4c and EVO (Staar Surgical), with a correction of -18.00 D. Bioptics were performed at least 3 months after implantation, and patients were followed up for at least 3 months after LASIK or PRK. RESULTS: The analysis included 125 eyes from 90 patients. Of these, 51.2% underwent LASIK and 48.8% PRK. Mean time from implantation to bioptics was 5.9 ± 9.4 months. Patients were followed up for a mean of 40.2 ± 37.9 months after bioptics. Median manifest refractive spherical equivalent was -2.89 D before bioptics and -0.49 D after. Median CDVA was 0.18 logMAR before bioptics and 0.17 after. The mean safety and efficacy indices were 2.22 ± 1.88 and 2.06 ± 1.85, respectively. CONCLUSION: Visual outcomes and safety indices following ICL implantation and subsequent LASIK or PRK in patients with extreme myopia are excellent.

Pituitary cryptococcoma in an immunocompetent patient with panhypopituitarism: illustrative case.

BACKGROUND: Cryptococcosis is the most common mycosis of the central nervous system. It may develop in immunocompetent and immunocompromised patients, the latter representing most cases. The most common presentation of the disease is meningitis, whereas intra-axial lesions in the form of cryptococcoma are less frequent with a greater tendency to present in immunocompetent patients. The presentation of pituitary cryptococcoma is exceptional. To the best of the authors' knowledge, there is only one case published in the medical literature. OBSERVATIONS: The authors present the case of a 30-year-old male without a relevant medical history. He was referred to our center with a pituitary mass on magnetic resonance imaging and panhypopituitarism. The patient underwent endonasal endoscopic transsphenoidal tumor resection, and a histopathological diagnosis of pituitary cryptococcoma was made. Medical management included fluconazole and intravenous amphotericin. LESSONS: This case underscores the neurosurgical and medical management of an exceptional clinical presentation of pituitary cryptococcoma in an immunocompetent patient. To the best of the authors' knowledge, there is only one case published in the medical literature. This case provides an invaluable review of the clinical, imaging, and therapeutic considerations regarding this exceptional clinical entity.

Uncovering perturbations in human hematopoiesis associated with healthy aging and myeloid malignancies at single-cell resolution.

Early hematopoiesis is a continuous process in which hematopoietic stem and progenitor cells (HSPCs) gradually differentiate toward specific lineages. Aging and myeloid malignant transformation are characterized by changes in the composition and regulation of HSPCs. In this study, we used single-cell RNA sequencing (scRNA-seq) to characterize an enriched population of human HSPCs obtained from young and elderly healthy individuals.Based on their transcriptional profile, we identified changes in the proportions of progenitor compartments during aging, and differences in their functionality, as evidenced by gene set enrichment analysis. Trajectory inference revealed that altered gene expression dynamics accompanied cell differentiation, which could explain aging-associated changes in hematopoiesis. Next, we focused on key regulators of transcription by constructing gene regulatory networks (GRNs) and detected regulons that were specifically active in elderly individuals. Using previous findings in healthy cells as a reference, we analyzed scRNA-seq data obtained from patients with myelodysplastic syndrome (MDS) and detected specific alterations of the expression dynamics of genes involved in erythroid differentiation in all patients with MDS such as TRIB2. In addition, the comparison between transcriptional programs and GRNs regulating normal HSPCs and MDS HSPCs allowed identification of regulons that were specifically active in MDS cases such as SMAD1, HOXA6, POU2F2, and RUNX1 suggesting a role of these transcription factors (TFs) in the pathogenesis of the disease.In summary, we demonstrate that the combination of single-cell technologies with computational analysis tools enable the study of a variety of cellular mechanisms involved in complex biological systems such as early hematopoiesis and can be used to dissect perturbed differentiation trajectories associated with perturbations such as aging and malignant transformation. Furthermore, the identification of abnormal regulatory mechanisms associated with myeloid malignancies could be exploited for personalized therapeutic approaches in individual patients.

Our blood contains many different types of cells; red blood cells carry oxygen through the body, platelets help to stop bleeding and a variety of white blood cells fight infections. All of these critical components come from a pool of immature cells in bone marrow, which can develop and specialise into any of these. However, as we get older, these immature cells can accumulate damage, including mutations in specific genes. This increases the risk of diseases such as myelodysplastic syndromes (MDS), a type of cancer in which the cells cannot develop and the patient does not have enough healthy mature blood cells. The changes in gene activity in the immature cells have previously been studied using samples from young and elderly people, as well as individuals with MDS. These studies examined large numbers of cells together, revealing differences between young and elderly people, and individuals with MDS. However, this does not describe how the different types alter their behaviour. To address this, Ainciburu, Ezponda et al. used a technique called single-cell RNA sequencing to study the gene activity in individual immature blood cells. This revealed changes associated with maturation that may account for the different combinations of cell populations in younger and older people. The results confirmed findings from previous studies and suggested new genes involved in ageing or MDS. Ainciburu, Ezponda et al. used these results to create an analytical system that highlights gene activity differences in individual MDS patients that are independent of age-related changes. These results provide new insights that could help further research into the development of MDS and the ageing process. In addition, scientists could study other diseases using this approach of analysing individual patients' gene activity. In future, this could help to personalise clinical decisions on diagnosis and treatment.

Efficacy of cabergoline therapy in patients with non-functioning pituitary adenomas: A single center clinical experience.

Introduction: To evaluate the response to cabergoline (CBG) treatment in patients with non-functioning pituitary adenomas (NFPA). Subjects and methods: Retrospective, single tertiary care center study. A total of 44 patients were treated with 3 mg/week of CBG, 32 after surgical treatment (transsphenoidal surgery [TSS] in 27 and TC in 5 patients) and 12 as primary therapy. Mean age was 59.2 ± 12 years and 23 (52.2%) were women. Response to therapy was ascertained by serial magnetic resonance imaging. The median duration of CBG therapy was 30 months (IQR 24-48). Response to CBG therapy was defined as a greater than 20% reduction in tumor size and volume. Results: A significant reduction in tumor size was documented in 29 patients (66%), whereas in 11 patients (25%) the tumor increased in size and in 4 (9%), it remained stable. Significant tumor shrinkage was documented in 4 (33.3%) of 12 patients treated primarily and in 23 (71.8%) of those treated secondarily. The three-year progression-free survival was 0.61. Conclusion: Cabergoline therapy is effective in reducing tumor growth in over two thirds of patients with NFPA, however 16% of patients will escape to this beneficial effect and will require alternative forms of treatment to halt tumor progression.

The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas.

Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poorly understood. To better understand the genomic landscape of all the lesions of the corticotroph lineage, we sequenced the whole exome of three SCA, one CCA, four ACTH-secreting PA causing CD, one corticotrophinoma occurring in a CD patient who developed Nelson syndrome after adrenalectomy and one patient with an ACTH-producing CA. The ACTH-producing CA was the lesion with the highest number of single nucleotide variants (SNV) in genes such as USP8, TP53, AURKA, EGFR, HSD3B1 and CDKN1A. The USP8 variant was found only in the ACTH-CA and in the corticotrophinoma occurring in a patient with Nelson syndrome. In CCA, SNV in TP53, EGFR, HSD3B1 and CDKN1A SNV were present. HSD3B1 and CDKN1A SNVs were present in all three SCA, whereas in two of these tumors SNV in TP53, AURKA and EGFR were found. None of the analyzed tumors showed SNV in USP48, BRAF, BRG1 or CABLES1. The amplification of 17q12 was found in all tumors, except for the ACTH-producing carcinoma. The four clinically functioning ACTH adenomas and the ACTH-CA shared the amplification of 10q11.22 and showed more copy-number variation (CNV) gains and single-nucleotide variations than the nonfunctioning tumors.

The kinome, cyclins and cyclin-dependent kinases of pituitary adenomas, a look into the gene expression profile among tumors from different lineages.

BACKGROUND: Pituitary adenomas (PA) are the second most common intracranial tumors and are classified according to hormone they produce, and the transcription factors they express. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. METHODS: Here we performed transcriptome and proteome analysis of tumors derived from POU1F1 (GH-, TSH-, and PRL-tumors, N = 16), NR5A1 (gonadotropes and null cells adenomas, n = 17) and TBX19 (ACTH-tumors, n = 6) lineages as well as from silent ACTH-tumors (n = 3) to determine expression of kinases, cyclins, CDKs and CDK inhibitors. RESULTS: The expression profiles of genes encoding kinases were distinctive for each of the three PA lineage: NR5A1-derived tumors showed upregulation of ETNK2 and PIK3C2G and alterations in MAPK, ErbB and RAS signaling, POU1F1-derived adenomas showed upregulation of PIP5K1B and NEK10 and alterations in phosphatidylinositol, insulin and phospholipase D signaling pathways and TBX19-derived adenomas showed upregulation of MERTK and STK17B and alterations in VEGFA-VEGFR, EGF-EGFR and Insulin signaling pathways. In contrast, the expression of the different genes encoding cyclins, CDK and CDK inhibitors among NR5A1-, POU1F1- and TBX19-adenomas showed only subtle differences. CDK9 and CDK18 were upregulated in NR5A1-adenomas, whereas CDK4 and CDK7 were upregulated in POUF1-adenomas. CONCLUSIONS: The kinome of PA clusters these lesions into three distinct groups according to the transcription factor that drives their terminal differentiation. And these complexes could be harnessed as molecular therapy targets.

Laser corneal enhancement after trifocal intraocular lens implantation in eyes that previously had photoablative corneal refractive surgery.

PURPOSE: To evaluate the visual and refractive outcomes of laser corneal enhancement after trifocal intraocular lens (IOL) implantation in eyes previously treated with myopic/hyperopic laser corneal refractive surgery (LCRS). SETTING: Clinica Baviera-AIER-Eye Group, Spain. DESIGN: Retrospective comparative case series. METHODS: Patients were divided by primary LCRS into myopic and hyperopic groups. The outcomes evaluated were uncorrected distance (UDVA), corrected distance (CDVA), uncorrected intermediate (UIVA), and uncorrected near visual acuity (UNVA), and predictability, safety, efficacy, and satisfaction after implantation of 2 trifocal IOL models (Physiol-FineVision and Zeiss-ATLisa 839) and subsequent laser enhancement. RESULTS: 186 eyes (89 myopic and 97 hyperopic eyes) from 146 patients were assessed. At the last visit, refractive outcomes were better in myopic than those in hyperopic eyes, with statistically significant differences for sphere ( P < .001), cylinder ( P < .001), manifest refraction spherical equivalent (MRSE) ( P = .003), CDVA ( P = .005), UDVA ( P = .047), and UNVA ( P = .003) but not for UIVA ( P = .580), binocular UIVA ( P = .660), or binocular UNVA ( P = .836). Predictability differences were nonsignificant between groups for a final MRSE of ±0.5 diopters (D) and ±1.0 D (P = .167 and .502, respectively). Efficacy and safety were similar in both groups ( P = .235 and P = .080). A greater myopic MRSE was present after trifocal implantation in myopic than in hyperopic eyes (MRSE = -0.93 vs -0.69 D, P = .013), and the statistically significant differences were maintained after enhancement between both groups (MRSE -0.00 vs 0.00 D, P = .003). Overall satisfaction was similar in both groups ( P > .05 all items). CONCLUSIONS: Corneal laser enhancement after implantation of a trifocal IOL in eyes previously treated for myopia or hyperopia with LCRS was safe, effective, predictable, and highly satisfactory.

Separation Iron(III)-Manganese(II) via Supported Liquid Membrane Technology in the Treatment of Spent Alkaline Batteries.

In this paper, the transport of iron(III) from iron(III)-manganese(II)-hydrochloric acid mixed solutions, coming from the treatment of spent alkaline batteries through a flat-sheet supported liquid membrane, is investigated (the carrier phase being of Cyanex 923 (commercially available phosphine oxide extractant) dissolved in Solvesso 100 (commercially available diluent)). Iron(III) transport is studied as a function of hydrodynamic conditions, the concentration of manganese and HCl in the feed phase, and the carrier concentration in the membrane phase. A transport model is derived that describes the transport mechanism, consisting of diffusion through a feed aqueous diffusion layer, a fast interfacial chemical reaction, and diffusion of the iron(III) species-Cyanex 923 complex across the membrane phase. The membrane diffusional resistance (Δm) and feed diffusional resistance (Δf) are calculated from the model, and their values are 145 s/cm and 361 s/cm, respectively. It is apparent that the transport of iron(III) is mainly controlled by diffusion through the aqueous feed boundary layer, this being the thickness of this layer calculated as 2.9 × 10-3 cm. Since manganese(II) is not transported through the membrane phase, the present system allows the purification of these manganese-bearing solutions.

Dynamic assessment of variations in pupil diameter using swept-source anterior segment optical coherence tomography after phakic collamer lens implantation.

PURPOSE: To dynamically assess variations in pupil diameter induced by changes in brightness in myopic eyes implanted with an implantable collamer lens (ICL, STAAR Surgical) with a central port. METHODS: This prospective, observational single-center case series study comprised 65 eyes from 65 consecutive patients undergoing ICL implant. A modified commercially available swept-source Fourier-domain anterior segment optical coherence tomography (AS-OCT) device was used for imaging and performing dynamic pupillometry under changing light conditions before and after a mean follow-up interval of four months after surgery. RESULTS: Preoperative mean pupil size under photopic conditions was 3.38 ± 0.64 mm; after surgery, this increased to 3.48 ± 0.61 mm. Mean pupil size under scotopic light conditions was 5.72 ± 0.79 mm before surgery and 5.84 ± 0.77 mm postoperatively. The differences between preoperative and postoperative pupil diameter in miosis and mydriasis were 0.10 ± 0.44 mm (P = 0.078) and 0.12 ± 0.58 mm (P = 0.098), respectively. The scotopic pupil exceeded the optic zone of the implanted lens in 39 eyes (60%). The mean central vault value was 412 ± 177 µm under maximum miosis and 506 ± 190 µm under maximum mydriasis. We found a positive correlation between vault and differences in pupil diameter under all light conditions (P < 0.05). CONCLUSION: Dynamic AS-OCT enables a very precise determination of the pupillary diameter in the iris plane. The changes in the pupil diameter under different light conditions after the implantation of an ICL are related to the postoperative vault.

Case Report: Double Intrastromal Corneal Ring Segment and Posterior Chamber Phakic Intraocular Lens Implantation.

SIGNIFICANCE: Keratoconus can manifest asymmetrically, affecting binocularity and becoming a refractive problem that is sometimes complex to solve. We propose a therapeutic approach for correction of keratoconus based on parallel implantation of a second intrastromal corneal ring segment (ICRS). PURPOSE: This study aimed to improve the refractive status of a patient affected with advanced bilateral keratoconus using implantation of a second ICRS and a phakic intraocular lens. CASE REPORT: A 44-year-old man came to our clinic requesting a refractive solution for his visual impairment. He had been diagnosed with bilateral severe keratoconus categorized by the Amsler-Krumeich classification scale as grade III (right eye) and grade II (left eye). He had previously undergone corneal cross-linking and implantation of ICRS (Intacs) in both eyes. Significant anisometropia was present between the eyes, and the patient also complained of poor quality of vision. We decided to implant a posterior chamber phakic collamer lens in his right eye and to insert a new ICRS (Keraring) deep and parallel to the previous one in his left eye. We aimed to prevent anisometropia in his right eye and to further regularize the affected cornea in his left eye. Refractive symmetry was achieved, and vision was optimized after surgery. CONCLUSIONS: In a patient with keratoconus, refractive surgery should be performed from a bilateral perspective. Specific cases of keratoconus can be managed by parallel implantation of a second ICRS.

Long-term assessment of crystalline lens transparency in eyes implanted with a central-hole phakic collamer lens developing low postoperative vault.

PURPOSE: To assess long-term crystalline lens transparency in eyes implanted with phakic collamer intraocular lens (pIOL) with a central port and low postoperative vault for correction of myopia. SETTING: Clinica Baviera, Madrid, Spain. DESIGN: Retrospective cross-sectional single-center study. METHODS: Using a noninvasive Fourier-domain swept-source anterior segment optical coherence tomography system, shifts in myopic and astigmatic myopic eyes implanted with a pIOL with vaulting lower than 100 µm in miosis and more than 4 years of follow-up were dynamically evaluated. Main outcome measures were pIOL dynamic vault (vault interval and vault range [VR]), crystalline lens density, and anterior subcapsular lens opacities. Crystalline lenses were examined under slitlamp microscopy, and lens density was evaluated using quantitative Scheimpflug images. Scheimpflug images were compared with those of a control group comprising eyes that were candidates for pIOL implantation. RESULTS: The study population comprised 24 eyes from 16 patients previously implanted with a pIOL (5.82 ± 0.9 years) with central vault lower than 100 µm under photopically induced miosis. The mean vault value was 52 ± 19 µm under photopic light conditions and 113 ± 37 µm under scotopic conditions. The mean VR was 58 ± 24 µm. Anterior subcapsular lens opacities were found in only 1 eye (4.17%). The mean lens density was 7.94 ± 0.43, and no statistically significant differences were observed compared with the control group. CONCLUSIONS: Long-term low vaulting in eyes implanted with a pIOL with a central port for correction of myopia was associated with a low risk for developing anterior crystalline lens opacities.

Proteomic and Transcriptomic Analysis Identify Spliceosome as a Significant Component of the Molecular Machinery in the Pituitary Tumors Derived from POU1F1- and NR5A1-Cell Lineages.

BACKGROUND: Pituitary adenomas (PA) are the second most common tumor in the central nervous system and have low counts of mutated genes. Splicing occurs in 95% of the coding RNA. There is scarce information about the spliceosome and mRNA-isoforms in PA, and therefore we carried out proteomic and transcriptomic analysis to identify spliceosome components and mRNA isoforms in PA. METHODS: Proteomic profile analysis was carried out by nano-HPLC and mass spectrometry with a quadrupole time-of-flight mass spectrometer. The mRNA isoforms and transcriptomic profiles were carried out by microarray technology. With proteins and mRNA information we carried out Gene Ontology and exon level analysis to identify splicing-related events. RESULTS: Approximately 2000 proteins were identified in pituitary tumors. Spliceosome proteins such as SRSF1, U2AF1 and RBM42 among others were found in PA. These results were validated at mRNA level, which showed up-regulation of spliceosome genes in PA. Spliceosome-related genes segregate and categorize PA tumor subtypes. The PA showed alterations in CDK18 and THY1 mRNA isoforms which could be tumor specific. CONCLUSIONS: Spliceosome components are significant constituents of the PA molecular machinery and could be used as molecular markers and therapeutic targets. Splicing-related genes and mRNA-isoforms profiles characterize tumor subtypes.

Transcriptome and methylome analysis reveals three cellular origins of pituitary tumors.

Pituitary adenomas (PA) are the second most common intracranial tumors. These neoplasms are classified according to the hormone they produce. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. The present transcriptomic and methylomic analysis of PA revealed that they segregate into three molecular clusters according to the transcription factor driving their terminal differentiation. First cluster, driven by NR5A1, consists of clinically non-functioning PA (CNFPA), comprising gonadotrophinomas and null cell; the second cluster consists of clinically evident ACTH adenomas and silent corticotroph adenomas, driven by TBX19; and the third, POU1F1-driven TSH-, PRL- and GH-adenomas, segregated together. Genes such as CACNA2D4, EPHA4 and SLIT1, were upregulated in each of these three clusters, respectively. Pathway enrichment analysis revealed specific alterations of these clusters: calcium signaling pathway in CNFPA; renin-angiotensin system for ACTH-adenomas and fatty acid metabolism for the TSH-, PRL-, GH-cluster. Non-tumoral pituitary scRNAseq data confirmed that this clustering also occurs in normal cytodifferentiation. Deconvolution analysis identify potential mononuclear cell infiltrate in PA consists of dendritic, NK and mast cells. Our results are consistent with a divergent origin of PA, which segregate into three clusters that depend on the specific transcription factors driving late pituitary cytodifferentiation.

Mapeamento dos profissionais de saúde no Brasil: alguns apontamentos em vista da crise sanitária da Covid-19 / Nota Técnica n. 30 (Diest) : Mapeamento dos profissionais de saúde no Brasi : alguns apontamentos em vista da crise sanitária da Covid-19

Apresenta dados que contribuem para a análise da capacidade do Estado brasileiro no enfrentamento da pandemia do vírus da Covid-19. O enfoque definido para o estudo foi examinar a distribuição estadual de algumas das principais categorias de profissionais da área da saúde em território nacional. Partindo de dados de vínculos de trabalho e pessoas nas ocupações de médicos, enfermeiros e agentes de saúde extraídos das séries anuais da Relação Anual de Informações Sociais do Ministério da Economia (Rais/ME), na versão aprimorada pelo Atlas do Estado Brasileiro, o estudo apresenta um retrato de assimetria na distribuição dessa força de trabalho entre os estados da Federação, assim como de ocupação entre os setores público e privado, com e sem fins lucrativos.

Extraction of polyphenols and synthesis of new activated carbon from spent coffee grounds.

A valorization process of spent coffee grounds (SCG) was studied. Thus, a two-stage process, the first stage of polyphenols extraction and synthesis of a carbonaceous precursor and a subsequent stage of obtaining activated carbon (AC) by means of a carbonization process from the precursor of the previous stage, was performed. The extraction was carried out with a hydro-alcoholic solution in a pressure reactor, modifying time, temperature and different mixtures EtOH:H2O. To optimize the polyphenols extraction, a two-level factorial experimental design with three replicates at the central point was used. The best results were obtained by using a temperature of 80 °C during 30 min with a mixture of EtOH:H2O 50:50 (v/v). Caffeine and chlorogenic acid were the most abundant compounds in the analysed extracts, ranging from 0.09 to 4.8 mg∙g-1 and 0.06 to 9.7 mg∙g-1, respectively. Similarly, an experimental design was realized in order to analyze the influence of different variables in the AC obtained process (reaction time, temperature and KOH:precursor ratio). The best results were 1 h, 850 °C, and a mixture of 2.5:1. The obtained activated carbons exhibit a great specific surface (between 1600 m2∙g-1 and 2330 m2∙g-1) with a microporous surface. Finally, the adsorption capacity of the activated carbons was evaluated by methylene blue adsorption.

Outcomes of Flap Lift Laser In Situ Keratomileusis Enhancements in a Large Patient Population: Does Application of a Bandage Contact Lens Affect Incidence of Epithelial Ingrowth?

PURPOSE: To compare the incidence of corneal epithelial ingrowth (EIG) and the visual outcomes of enhancement with laser in situ keratomileusis (LASIK) by flap lift when a bandage soft contact lens (CL) was fitted after the procedure and when it was not. METHODS: This is a multicenter, retrospective, interventional case series in which all patients who underwent LASIK enhancement from January 2005 to January 2015 were included consecutively. Patients were grouped depending on whether a bandage CL was fitted after re-treatment by flap lift (group 1) or not (group 2). RESULTS: A total of 16,702 eyes from 12,485 patients were included. There were statistically significant differences between the groups regarding corrected distance visual acuity (better in group 1) and safety index (better in group 2) although these were not clinically relevant. The incidence of EIG was 0.58% in group 1 and 0.55% in group 2 although, again, the difference was not statistically different. CONCLUSIONS: We found no relevant differences in LASIK enhancement between patients who received a bandage CL and those who did not regarding the incidence of EIG and visual outcomes.