Posterior Lamellar Graft Preparation: A Prospective Review from an Eye Bank on Current and Future Aspects

Descemet membrane endothelial keratoplasty (DMEK) is a corneal surgical technique which selectively replaces the damaged posterior part of the cornea with a healthy donor graft retaining the rest of the tissue intact. There is a need to validate and standardize the donor tissue before grafting due to certain issues that can lead to consequences such as graft failure due to poor endothelial cell count, higher mortality, detachment of the graft, or increased surgical expenses, time, and effort. Thus, prospective potential surgeons and eye banks should now aim at developing new improved surgical techniques in order to prepare the best suited, validated, precut, preloaded, and easy to transplant tissue to reduce pre- and postsurgical complications. This could be achieved by defining parameters like graft thickness, accepted mortality threshold of the endothelial cells, and behavior of grafts during preservation and transportation along with using more sophisticated instruments like microkeratome and femtosecond lasers for graft preparation. Thus, a rapport between the eye banks and the surgeons along with the advanced instruments can overcome this challenge to find the best possible solution for endothelial keratoplasty (EK)

Health Status and Patient Satisfaction after Corneal Graft: Results from the Corneal Transplant Epidemiological Study

Purpose. To evaluate effects of corneal transplantation on the health-related quality of life and patients' satisfaction. Methods. Patients scheduled for elective penetrating or anterior lamellar keratoplasty completed by telephone interview the SF-12 Health Survey, before and one year after surgery, and a 6-item questionnaire on the satisfaction for graft outcomes. Results. The two questionnaires were answered by 1,223 patients. Transplantation did not influence the PCS-12 in males (ES = −0.01) and had a negative effect in females (ES = −0.18). Both sexes improved their MCS-12 (ES = 0.18 and 0.23, resp.). The majority of patients (83.1%) were satisfied by the outcome of the graft. Conclusions. This is the first report on the use of the SF-12 and one of the few that assess quality of life in patients after corneal transplantation. We showed that grafting improves patients' health-related quality of life results of patients, influencing mental health (i.e., psychological attitude, social interaction, and emotions) with minor effects on physical health (limitation, pain, and vitality)

Substrate reduction therapy with Miglustat in pediatric patients with GM1 type 2 gangliosidosis delays neurological involvement: A multicenter experience

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A sex-informed approach to improve the personalised decision making process in myelodysplastic syndromes: a multicentre, observational cohort study

Background Sex is a major source of diversity among patients and a sex-informed approach is becoming a new paradigm in precision medicine. We aimed to describe sex diversity in myelodysplastic syndromes in terms of disease genotype, phenotype, and clinical outcome. Moreover, we sought to incorporate sex information into the clinical decision-making process as a fundamental component of patient individuality. Methods In this multicentre, observational cohort study, we retrospectively analysed 13 284 patients aged 18 years or older with a diagnosis of myelodysplastic syndrome according to 2016 WHO criteria included in the EuroMDS network (n=2025), International Working Group for Prognosis in MDS (IWG-PM; n=2387), the Spanish Group of Myelodysplastic Syndromes registry (GESMD; n=7687), or the Dusseldorf MDS registry (n=1185). Recruitment periods for these cohorts were between 1990 and 2016. The correlation between sex and genomic features was analysed in the EuroMDS cohort and validated in the IWG-PM cohort. The effect of sex on clinical outcome, with overall survival as the main endpoint, was analysed in the EuroMDS population and validated in the other three cohorts. Finally, novel prognostic models incorporating sex and genomic information were built and validated, and compared to the widely used revised International Prognostic Scoring System (IPSS-R). This study is registered with ClinicalTrials.gov, NCT04889729. Findings The study included 7792 (58middot7%) men and 5492 (41middot3%) women. 10 906 (82middot1%) patients were White, and race was not reported for 2378 (17middot9%) patients. Sex biases were observed at the single-gene level with mutations in seven genes enriched in men (ASXL1, SRSF2, and ZRSR2 p<0middot0001 in both cohorts; DDX41 not available in the EuroMDS cohort vs p=0middot0062 in the IWG-PM cohort; IDH2 p<0middot0001 in EuroMDS vs p=0middot042 in IWG-PM; TET2 p=0middot031 vs p=0middot035; U2AF1 p=0middot033 vs p<0middot0001) and mutations in two genes were enriched in women (DNMT3A p<0middot0001 in EuroMDS vs p=0middot011 in IWG-PM; TP53 p=0middot030 vs p=0middot037). Additionally, sex biases were observed in co-mutational pathways of founding genomic lesions (splicing-related genes, predominantly in men, p<0middot0001 in both the EuroMDS and IWG-PM cohorts), in DNA methylation (predominantly in men, p=0middot046 in EuroMDS vs p<0middot0001 in IWG-PM), and TP53 mutational pathways (predominantly in women, p=0middot0073 in EuroMDS vs p<0middot0001 in IWG-PM). In the retrospective EuroMDS cohort, men had worse median overall survival (81middot3 months, 95% CI 70middot4-95middot0 in men vs 123middot5 months, 104middot5-127middot5 in women; hazard ratio [HR] 1middot40, 95% CI 1middot26-1middot52; p<0middot0001). This result was confirmed in the prospective validation cohorts (median overall survival was 54middot7 months, 95% CI 52middot4-59middot1 in men vs 74middot4 months, 69middot3-81middot2 in women; HR 1middot30, 95% CI 1middot23-1middot35; p<0middot0001 in the GEMSD MDS registry; 40middot0 months, 95% CI 33middot4-43middot7 in men vs 54middot2 months, 38middot6-63middot8 in women; HR 1middot23, 95% CI 1middot08-1middot36; p<0middot0001 in the Dusseldorf MDS registry). We developed new personalised prognostic tools that included sex information (the sex-informed prognostic scoring system and the sex-informed genomic scoring system). Sex maintained independent prognostic power in all prognostic systems; the highest performance was observed in the model that included both sex and genomic information. A five-to-five mapping between the IPSS-R and new score categories resulted in the re-stratification of 871 (43middot0%) of 2025 patients from the EuroMDS cohort and 1003 (42middot0%) of 2387 patients from the IWG-PM cohort by using the sex-informed prognostic scoring system, and of 1134 (56middot0%) patients from the EuroMDS cohort and 1265 (53middot0%) patients from the IWG-PM cohort by using the sex-informed genomic scoring system. We created a web portal that enables outcome predictions based on a sex-informed personalised approach. Interpretation Our results suggest that a sex-informed approach can improve the personalised decision making process in patients with myelodysplastic syndromes and should be considered in the design of clinical trials including low-risk patients. Copyright (c) 2022 Published by Elsevier Ltd. All rights reserved

Category-Specific Organization in the Human Brain Does Not Require Visual Experience

Distinct regions within the ventral visual pathway show neural specialization for nonliving and living stimuli (e.g., tools, houses versus animals, faces). The causes of these category preferences are widely debated. Using functional magnetic resonance imaging, we find that the same regions of the ventral stream that show category preferences for nonliving stimuli and animals in sighted adults show the same category preferences in adults who are blind since birth. Both blind and sighted participants had larger blood oxygen-level dependent (BOLD) responses in the medial fusiform gyrus for nonliving stimuli compared to animal stimuli and differential BOLD responses in lateral occipital cortex for animal stimuli compared to nonliving stimuli. These findings demonstrate that the medial-to-lateral bias by conceptual domain in the ventral visual pathway does not require visual experience in order to develop and suggest the operation of innately determined domain-specific constraints on the organization of object knowledge.Psycholog

Health Status and Patient Satisfaction after Corneal Graft: Results from the Corneal Transplant Epidemiological Study

. Purpose. To evaluate effects of corneal transplantation on the health-related quality of life and patients&apos; satisfaction. Methods. Patients scheduled for elective penetrating or anterior lamellar keratoplasty completed by telephone interview the SF-12 Health Survey, before and one year after surgery, and a 6-item questionnaire on the satisfaction for graft outcomes. Results. The two questionnaires were answered by 1,223 patients. Transplantation did not influence the PCS-12 in males (ES = −0.01) and had a negative effect in females (ES = −0.18). Both sexes improved their MCS-12 (ES = 0.18 and 0.23, resp.). The majority of patients (83.1%) were satisfied by the outcome of the graft. Conclusions. This is the first report on the use of the SF-12 and one of the few that assess quality of life in patients after corneal transplantation. We showed that grafting improves patients&apos; health-related quality of life results of patients, influencing mental health (i.e., psychological attitude, social interaction, and emotions) with minor effects on physical health (limitation, pain, and vitality)

A sex-informed approach to improve the personalised decision making process in myelodysplastic syndromes : a multicentre, observational cohort study

Altres ajuts: the AIRC Foundation (Associazione Italiana per la Ricerca contro il Cancro; Milan, Italy; projects #22053 to MGDP, #26216 to GC, and #21267 to MTV), PRIN 2017 (Ministry of University and Research, Italy; project 2017WXR7ZT to MGDP), Ricerca Finalizzata 2016 and 2018 (Italian Ministry of Health, Italy; projects RF2016-02364918 to MGDP and NET-2018-12365935 to MGDP, FP, and MTV), the Cariplo Foundation (Milan, Italy; project #2016-0860 to MGDP), and the Beat Leukemia Foundation (Milan, Italy; to MGDP).Background: Sex is a major source of diversity among patients and a sex-informed approach is becoming a new paradigm in precision medicine. We aimed to describe sex diversity in myelodysplastic syndromes in terms of disease genotype, phenotype, and clinical outcome. Moreover, we sought to incorporate sex information into the clinical decision-making process as a fundamental component of patient individuality. Methods: In this multicentre, observational cohort study, we retrospectively analysed 13 284 patients aged 18 years or older with a diagnosis of myelodysplastic syndrome according to 2016 WHO criteria included in the EuroMDS network (n=2025), International Working Group for Prognosis in MDS (IWG-PM; n=2387), the Spanish Group of Myelodysplastic Syndromes registry (GESMD; n=7687), or the Düsseldorf MDS registry (n=1185). Recruitment periods for these cohorts were between 1990 and 2016. The correlation between sex and genomic features was analysed in the EuroMDS cohort and validated in the IWG-PM cohort. The effect of sex on clinical outcome, with overall survival as the main endpoint, was analysed in the EuroMDS population and validated in the other three cohorts. Finally, novel prognostic models incorporating sex and genomic information were built and validated, and compared to the widely used revised International Prognostic Scoring System (IPSS-R). This study is registered with ClinicalTrials.gov, NCT04889729. Findings: The study included 7792 (58·7%) men and 5492 (41·3%) women. 10 906 (82·1%) patients were White, and race was not reported for 2378 (17·9%) patients. Sex biases were observed at the single-gene level with mutations in seven genes enriched in men (ASXL1, SRSF2, and ZRSR2 p<0·0001 in both cohorts; DDX41 not available in the EuroMDS cohort vs p=0·0062 in the IWG-PM cohort; IDH2 p<0·0001 in EuroMDS vs p=0·042 in IWG-PM; TET2 p=0·031 vs p=0·035; U2AF1 p=0·033 vs p<0·0001) and mutations in two genes were enriched in women (DNMT3A p<0·0001 in EuroMDS vs p=0·011 in IWG-PM; TP53 p=0·030 vs p=0·037). Additionally, sex biases were observed in co-mutational pathways of founding genomic lesions (splicing-related genes, predominantly in men, p<0·0001 in both the EuroMDS and IWG-PM cohorts), in DNA methylation (predominantly in men, p=0·046 in EuroMDS vs p<0·0001 in IWG-PM), and TP53 mutational pathways (predominantly in women, p=0·0073 in EuroMDS vs p<0·0001 in IWG-PM). In the retrospective EuroMDS cohort, men had worse median overall survival (81·3 months, 95% CI 70·4-95·0 in men vs 123·5 months, 104·5-127·5 in women; hazard ratio [HR] 1·40, 95% CI 1·26-1·52; p<0·0001). This result was confirmed in the prospective validation cohorts (median overall survival was 54·7 months, 95% CI 52·4-59·1 in men vs 74·4 months, 69·3-81·2 in women; HR 1·30, 95% CI 1·23-1·35; p<0·0001 in the GEMSD MDS registry; 40·0 months, 95% CI 33·4-43·7 in men vs 54·2 months, 38·6-63·8 in women; HR 1·23, 95% CI 1·08-1·36; p<0·0001 in the Dusseldorf MDS registry). We developed new personalised prognostic tools that included sex information (the sex-informed prognostic scoring system and the sex-informed genomic scoring system). Sex maintained independent prognostic power in all prognostic systems; the highest performance was observed in the model that included both sex and genomic information. A five-to-five mapping between the IPSS-R and new score categories resulted in the re-stratification of 871 (43·0%) of 2025 patients from the EuroMDS cohort and 1003 (42·0%) of 2387 patients from the IWG-PM cohort by using the sex-informed prognostic scoring system, and of 1134 (56·0%) patients from the EuroMDS cohort and 1265 (53·0%) patients from the IWG-PM cohort by using the sex-informed genomic scoring system. We created a web portal that enables outcome predictions based on a sex-informed personalised approach. Interpretation: Our results suggest that a sex-informed approach can improve the personalised decision making process in patients with myelodysplastic syndromes and should be considered in the design of clinical trials including low-risk patients. Funding: European Union (Horizon 2020 and Transcan programs), Italian Association for Cancer Research, Italian Ministry of Health, and Italian Ministry of University and Research