A Report of a Rare Case of BCOR (B-cell Line 6 Corepressor)-Altered Sarcoma of the Lung in a Child.

Ewing sarcoma is one of the small round blue cell tumors of childhood that typically affects bone. Recently, a subgroup of undifferentiated round-cell sarcomas has been genetically identified as BCOR (B-cell Line 6 Corepressor)-altered sarcomas (BAS). We present a case of a six-year-old male child who presented with a chief complaint of shortness of breath and tachypnea and was found to have a large mediastinal mass concerning sarcoma. Preliminary biopsy results were positive for small round blue cells, possibly Ewing sarcoma. After six cycles of chemotherapy, with subsequent shrinkage of mediastinal mass, the patient was able to undergo wedge resection and excision of the mass with en bloc resection of the fifth and sixth rib, preserving his right lung. Final tissue pathology was positive for BAS. There have been only four reported cases of BAS of the chest wall and zero reported cases of primary tumor presentation of the lung, making this a rare presentation of the disease.

Visual Acuity Outcomes and Complications after Intraocular Lens Exchange: An IRIS® Registry (Intelligent Research in Sight) Analysis.

PURPOSE: To assess risk factors for worse visual acuity (VA) outcomes after intraocular lens (IOL) exchange, and the most common postsurgical complications. DESIGN: Retrospective cohort study. PARTICIPANTS: Eyes from patients 18 years of age and older in the IRIS® Registry (Intelligent Research in Sight) that underwent IOL exchange in the United States between 2013 and 2019. METHODS: Vision improvement compared with baseline was determined at 1 year after surgery. A multivariable generalized estimating equation model adjusting for demographic factors and baseline vision was used to identify factors associated with VA worse than 20/40 at 1 year. MAIN OUTCOME MEASURES: Visual outcomes and postoperative complications after lens exchange. RESULTS: A total of 46 063 procedures (n = 41 925 unique patients) were included in the analysis. Overall, VA improved from a mean ± standard deviation (SD) of 0.53 ± 0.58 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/70) before surgery to a mean ± SD of 0.31 ± 0.40 logMAR (Snellen equivalent, 20/40) at 1 year. Among eyes with VA recorded at both baseline and 1 year after surgery, 60.5% achieved VA of 20/40 or better at 1 year. Vision of worse than 20/40 at 1 year was associated with greater age (odds ratio [OR], 1.16 per 5-year increase; 95% confidence interval [CI], 1.14-1.18) and higher logMAR baseline VA (OR, 1.14 per 0.1-logMAR increase; 95% CI, 1.14-1.15), as well as Black or African American (OR, 1.96; 95% CI, 1.68-2.28), Hispanic (OR, 1.82; 95% CI, 1.59-2.08), and Asian (OR, 1.48; 95% CI, 1.21-1.81) race or ethnicity versus White race, Medicaid (OR, 1.78; 95% CI, 1.40-2.25) versus private insurance, smoking history (OR, 1.22; 95% CI, 1.11-1.35), and concurrent anterior (OR, 1.65; 95% CI, 1.51-1.81) and posterior (OR, 1.53; 95% CI, 1.41-1.66) vitrectomy versus no vitrectomy. Female sex was associated with better VA at 1 year. At 1 year, epiretinal membrane (10.9%), mechanical lens complication (9.4%), and dislocation of the replacement lens (7.1%) were the most common complications. CONCLUSIONS: In this large national cohort, the annual number of IOL exchanges rose steadily over time. Vision improved in 60.2% of patients; worse visual outcomes were associated with greater age, worse baseline vision, Black race, Hispanic ethnicity, Medicaid insurance, smoking, and concurrent vitrectomy. Epiretinal membrane was the most common complication. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Prevalence and Risk Factors of Blindness Among Primary Angle Closure Glaucoma Patients in the United States: An IRIS Registry Analysis.

PURPOSE: To assess the prevalence and risk factors of blindness among patients newly diagnosed with primary angle closure glaucoma (PACG) in the United States. DESIGN: Retrospective cross-sectional study. METHODS: Eligible patients from the American Academy of Ophthalmology (AAO) Intelligent Research in Sight (IRIS) Registry had newly diagnosed PACG, defined as: 1) observable during a 24-month lookback period from index date of PACG diagnosis; 2) no history of eye drops, laser, or cataract surgery unless preceded by a diagnosis of anatomical narrow angle (ANA); and 3) no history of glaucoma surgery. Logistic regression models were developed to identify risk factors for any (one or both eyes) or bilateral (both eyes) blindness (visual acuity ≤20/200) at first diagnosis of PACG. RESULTS: Among 43,901 eligible patients, overall prevalence of any and bilateral blindness were 11.5% and 1.8%, respectively. Black and Hispanic patients were at higher risk of any (odds ratios [ORs] 1.42 and 1.21, respectively; P < .001) and bilateral (ORs 2.04 and 1.53, respectively; P < .001) blindness compared with non-Hispanic White patients adjusted for ocular comorbidities. Age <50 or >80 years, male sex, Medicaid or Medicare insurance product, and Southern or Western practice region also conferred a higher risk of blindness (OR > 1.28; P ≤ .01). CONCLUSIONS: Blindness affects 1 of 9 patients with newly diagnosed PACG in the IRIS Registry. Black and Hispanic patients and Medicaid and Medicare recipients are at significantly higher risk. These findings highlight the severe ocular morbidity among patients with PACG and the need for improved disease awareness and detection methods.

Mechanism of polycyclic aromatic hydrocarbons degradation in the rhizosphere of Phragmites australis: Organic acid co-metabolism, iron-driven, and microbial response.

Microbial co-metabolism is crucial for the efficient biodegradation of polycyclic aromatic hydrocarbons (PAHs); however, their intrinsic mechanisms remain unclear. To explore the co-metabolic degradation of PAHs, root organic acids (ROAs) (phenolic ROAs: caffeic acid [CA] and ferulic acid [FA]; non-phenolic ROAs: oxalic acid [OA]) were exogenously added as co-metabolic substrates under high (HFe) and low (LFe) iron levels in this study. The results demonstrated that more than 90% of PAHs were eliminated from the rhizosphere of Phragmites australis. OA can promote the enrichment of unrelated degrading bacteria and non-specific dioxygenases. FA with a monohydroxy structure can activate hydroxylase; however, it relies on phytosiderophores released by plants (such as OA) to adapt to stress. Therefore, non-specific co-metabolism occurred in these units. The best performance for PAH removal was observed in the HFe-CA unit because: (a) HFe concentrations enriched the Fe-reducing and denitrifying bacteria and promoted the rate-limiting degradation for PAHs as the enzyme cofactor; (b) CA with a dihydroxyl structure enriched the related degrading bacteria, stimulated specific dioxygenase, and activated Fe to concentrate around the rhizosphere simultaneously to perform the specific co-metabolism. Understanding the co-metabolic degradation of PAHs will help improve the efficacy of rhizosphere-mediated remediation.

Loss to Follow-up in Patients with Neovascular Age-Related Macular Degeneration Treated with Anti-VEGF Therapy in the United States in the IRIS® Registry.

PURPOSE: To determine the incidence of being lost to follow-up (LTFU) and nonpersistence in patients with neovascular age-related macular degeneration (AMD) treated with anti-VEGF injections in the United States. DESIGN: Retrospective cohort study using the IRIS® (Intelligent Research in Sight) Registry data. PARTICIPANTS: One hundred fifty-six thousand three hundred twenty-seven treatment-naive patients with neovascular AMD who subsequently were treated with anti-VEGF therapy from 2013 through 2015 and followed up through 2019. METHODS: Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: Being LTFU was defined as no follow-up within 12 months from last intravitreal injection. Nonpersistence was defined as no follow-up within 6 months from last intravitreal injection. RESULTS: For neovascular AMD, 11.6% of patients (95% CI, 11.4%-11.7%) were LTFU, and 88.4% of patients were followed up within 12 months. The rate of being LTFU generally was higher with increasing age, with odds of being LTFU greatest for patients between 81 and 84 years of age (OR, 2.51; 95% CI, 2.31-2.74; P < 0.001) compared with patients 70 years of age and younger. Odds of being LTFU for Black or African American patients (OR, 1.32; 95% CI, 1.08-1.61; P = 0.007) were greater than for White patients. Odds of being LTFU were higher for patients with Medicaid insurance (OR, 1.27; 95% CI, 1.01-1.60; P = 0.04) and lower for patients with Medicare Fee-For-Service insurance (OR, 0.69; 95% CI, 0.64-0.74; P < 0.001) than for patients with private insurance. Furthermore, 14.3% (95% CI, 14.1-14.4) of patients were nonpersistent, and 85.7% of patients underwent follow-up within 6 months. Odds of nonpersistence also were greatest among patients between 81 and 84 years of age (OR, 2.13; 95% CI, 1.98-2.29; P < 0.001) compared with patients 70 years of age or younger. Odds of nonpersistence for Black or African-American patients (OR, 1.38; 95% CI, 1.15-1.65; P < 0.001) and Hispanic patients (OR, 1.13; 95% CI, 1.03-1.24; P = 0.009) were greater than odds for White patients. CONCLUSIONS: Nearly 1 of 9 patients with neovascular AMD treated with anti-VEGF injections became LTFU, whereas 1 of 7 patients were nonpersistent. Risk factors identified included increasing age, male sex, unilateral involvement, diabetes, Medicaid insurance, and race or ethnicity. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Endoscopic Superior Peroneal Retinaculum Reconstruction Using Q-FIX MINI Suture Anchor.

Post-traumatic peroneal tendon subluxation or dislocation is most commonly caused by injury to the superior peroneal retinaculum. Classic open surgeries usually require extensive soft-tissue dissection and have potential risks of peritendinous fibrous adhesions, sural nerve injury, limited range of movement, recurrent or persistent peroneal tendon instability, and tendon irritation. The purpose of this Technical Note is to describe the details of endoscopic superior peroneal retinaculum reconstruction using Q-FIX MINI suture anchor. This endoscopic approach has the advantages of minimally invasive surgery, including better cosmesis, less soft-tissue dissection, less postoperative pain, less peritendinous fibrosis, and less subjective tightness at peroneal tendons. Insertion of the Q-FIX MINI suture anchor can be performed inside a drill guide, and trapping of the surrounding soft tissue can be avoided.

Vitreoretinopathy-Associated Pediatric Retinal Detachment Treatment Outcomes: IRIS® Registry (Intelligent Research in Sight) Analysis.

Purpose: To determine the treatment patterns and outcomes of pediatric retinal detachments (RDs) associated with hereditary vitreoretinopathies. Design: Retrospective cohort analysis using IRIS® Registry (Intelligent Research in Sight) database. Participants: Patients < 18 years old with a rhegmatogenous RD and a systemic disorder associated with vitreoretinal degeneration (e.g., Stickler syndrome) or other malformation of the vitreous from 2013-2019. Methods: Cases were identified using International Classification of Diseases, Ninth and Tenth Revisions (ICD-9, ICD-10) diagnostic codes from the IRIS® Registry cohort. Other hereditary vitreoretinopathies that are not encoded by specific ICD code(s) were captured by text search. Nonspecific vitreous abnormality ICD codes were also included. Exclusion criteria included traumatic retinal detachments using ICD codes for ocular trauma and serous or exudative retinal detachment. Surgical procedures were identified using Current Procedural Terminology (CPT) codes for repair of retinal detachment. Baseline demographic information collected included age, gender, race/ethnicity, geographic region of the provider location, and health insurance status. Main Outcome Measures: Main outcomes measured in this study were average time to first surgery, number of eyes presenting with bilateral detachments, and choice of initial surgical procedure. Results: A total of 2115 eyes of 1722 patients were identified (mean age, 10.4 years; 58% male). The median time to first surgery was 7 days (interquartile range, 40 days). One thousand four hundred seven eyes of 1134 patients had ≥ 1 year of follow-up, with 506 eyes (36%) developing a fellow eye RD. Thirty-three percent of patients presenting with bilateral detachments, and 349 eyes had initial RD surgery within 1 year of the index date documented by CPT code. Fellow eye detachment occurred a mean of 32 days after initial presentation. The mean number of surgeries per eye within 1 year was 1.68. Best-corrected visual acuity did not improve from a baseline 20/54 to 20/62. The initial procedure was most commonly complex RD repair (n = 176), followed by scleral buckle (n = 102), pars plana vitrectomy (n = 89), laser (n = 59), cryotherapy (n = 5), and pneumatic retinopexy (n = 5). There were 51 new diagnoses of glaucoma and 37 new diagnoses of aphakia within 1 year after the surgical procedure. Conclusions: IRIS Registry data provide insight into rare pediatric vitreoretinopathy-associated RDs, which have a high rate of reoperation and fellow eye involvement. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Emulating VIEW 1 and VIEW 2 Clinical Trial Outcome Data Using the American Academy of Ophthalmology IRIS Registry.

BACKGROUND AND OBJECTIVE: A retrospective, noninterventional cohort study of the American Academy of Ophthalmology IRIS Registry, an electronic health record (EHR)-based comprehensive eye disease and condition registry, intended to assess whether the IRIS® Registry (Intelligent Research in Sight) could emulate the VIEW randomized clinical trials (VIEW RCTs) eligibility criteria, treatment protocol regimen, and primary endpoint. PATIENTS AND METHODS: Deidentified patients having an anti-VEGF injection of aflibercept or ranibizumab between January 1, 2013, and December 31, 2018, from the IRIS Registry. Patients were treated in accordance with one of three treatment regimens from the VIEW RCT: monthly intravitreal aflibercept injection (IAI 2Q4), intravitreal aflibercept every 2 months after 3 initial monthly doses (IAI 2Q8), or monthly ranibizumab (RQ4) injection. The main outcome measures are the number and proportion of patients meeting VIEW RCT eligibility and treatment group criteria, demographic, and clinical differences between IRIS Registry treatment groups, mean change in best documented visual acuity at one year, and evaluation of the primary endpoint of the VIEW RCT: difference in the proportion of patients maintaining vision. RESULTS: Among the 90,900 patients who met VIEW RCT eligibility criteria, 4,457 (4.85%) met treatment group criteria. The percentage of patients maintaining vision at one year was over 90%. No statistically significant difference was observed when comparing the proportion of patients maintaining vision among the RQ4 treatment group to the IAI 2Q4 or IAI 2Q8 treatment group. CONCLUSIONS: A small percentage of real-world patients met VIEW RCT study eligibility criteria and treatment protocol regimen. Among patients meeting all available criteria, the primary endpoint interpretation yielded by an observational EHR-based dataset suggested comparable results to the VIEW RCT. [Ophthalmic Surg Lasers Imaging Retina 2023;54:6-14.].

Multiplex epigenome editing of MECP2 to rescue Rett syndrome neurons.

Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by loss-of-function heterozygous mutations of methyl CpG-binding protein 2 (MECP2) on the X chromosome in young females. Reactivation of the silent wild-type MECP2 allele from the inactive X chromosome (Xi) represents a promising therapeutic opportunity for female patients with RTT. Here, we applied a multiplex epigenome editing approach to reactivate MECP2 from Xi in RTT human embryonic stem cells (hESCs) and derived neurons. Demethylation of the MECP2 promoter by dCas9-Tet1 with target single-guide RNA reactivated MECP2 from Xi in RTT hESCs without detectable off-target effects at the transcriptional level. Neurons derived from methylation-edited RTT hESCs maintained MECP2 reactivation and reversed the smaller soma size and electrophysiological abnormalities, two hallmarks of RTT. In RTT neurons, insulation of the methylation-edited MECP2 locus by dCpf1-CTCF (a catalytically dead Cpf1 fused with CCCTC-binding factor) with target CRISPR RNA enhanced MECP2 reactivation and rescued RTT-related neuronal defects, providing a proof-of-concept study for epigenome editing to treat RTT and potentially other dominant X-linked diseases.

Comprehensive analyses of a tumor-infiltrating lymphocytes-related gene signature regarding the prognosis and immunologic features for immunotherapy in bladder cancer on the basis of WGCNA.

Tumor-infiltrating lymphocyte (TIL) is a class of cells with important immune functions and plays a crucial role in bladder cancer (BCa). Several studies have shown the clinical significance of TIL in predicting the prognosis and immunotherapy efficacy. TIL-related gene module was screened utilizing weighted gene coexpression network analysis. We screened eight TIL-related genes utilizing univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and multivariate Cox regression analysis. Then, we established a TIL-related signature model containing the eight selected genes and subsequently classified all patients into two groups, that is, the high-risk as well as low-risk groups. Gene mutation status, prognosis, immune cell infiltration, immune subtypes, TME, clinical features, and immunotherapy response were assessed among different risk subgroups. The results affirmed that the TIL-related signature model was a reliable predictor of overall survival (OS) for BCa and was determined as an independent risk factor for BCa patients in two cohorts. Moreover, the risk score was substantially linked to age, tumor staging, TNM stage, and pathological grade. And there were different mutational profiles, biological pathways, immune scores, stromal scores, and immune cell infiltration in the tumor microenvironment (TME) between the two risk groups. In particular, immune checkpoint genes' expression was remarkably different between the two risk groups, with patients belonging to the low-risk group responding better to immune checkpoint inhibition (ICI) therapy. In conclusion, our study demonstrates that the TIL-related model was a reliable signature in anticipating prognosis, immune status, and immunotherapy response, which can help in screening patients who respond to immunotherapy.

Ultra-high field 7 T MRI localizes regional brain volume recovery following corticotroph adenoma resection and hormonal remission in Cushing's disease: A case series.

Background: Cushing's disease (CD) is defined by glucocorticoid excess secondary to the increased section of corticotropin by a pituitary adenoma. Magnetic resonance imaging (MRI) studies performed at 1.5 or 3 Tesla (T) have demonstrated correlations between regional changes in brain structure and the progression of CD. In this report, we examine the changes in brain volume following corticotroph pituitary adenoma resection using ultra-high field 7 T MRI to increase the accuracy of our volumetric analyses. Methods: Thirteen patients were referred to the endocrinology clinic at our institution from 2017 to 2020 with symptoms of cortisol excess and were diagnosed with ACTH-dependent endogenous Cushing syndrome. Five patients had follow-up 7 T imaging at varying time points after a transsphenoidal resection. Results: Symmetrized percent change in regional volumes demonstrated a postoperative increase in cortical volume that was relatively larger than that of cerebral white matter or subcortical gray matter (percent changes = 0.0172%, 0.0052%, and 0.0120%, respectively). In the left cerebral hemisphere, the medial orbitofrontal, lateral orbitofrontal, and pars opercularis cortical regions experienced the most robust postoperative percent increases (percent changes = 0.0166%, 0.0122%, and 0.0068%, respectively). In the right cerebral hemisphere, the largest percent increases were observed in the pars triangularis, rostral portion of the middle frontal gyrus, and superior frontal gyrus (percent changes = 0.0156%, 0.0120%, and 0.0158%). Conclusion: Cerebral volume recovery following pituitary adenoma resection is driven by changes in cortical thickness predominantly in the frontal lobe, while subcortical white and gray matter volumes increase more modestly.

The Origin and Evolution of Bladder Cancer Stem Cells.

Bladder cancer is the most common malignant tumor of the urinary system. Bladder cancer stem cells (BCSCs) play key roles in tumor initiation, metastasis, relapse and drug-resistance. Investigation of BCSCs is of great value. On the basis of a review of normal bladder stem cells and universal cancer stem cells (CSCs), we summarize the origin of BCSCs, isolation and identification of CSCs from bladder cancer, signaling pathway of BCSCs, BCSCs targeted therapy, and relationship of BCSCs with non-muscle invasiveness and muscle invasiveness. This review aims to provide better elucidation about BCSCs, and provide constructive data for classification, prognosis, treatment and early intervention of bladder cancer.

Differential cofactor dependencies define distinct types of human enhancers.

All multicellular organisms rely on differential gene transcription regulated by genomic enhancers, which function through cofactors that are recruited by transcription factors1,2. Emerging evidence suggests that not all cofactors are required at all enhancers3-5, yet whether these observations reflect more general principles or distinct types of enhancers remained unknown. Here we categorized human enhancers by their cofactor dependencies and show that these categories provide a framework to understand the sequence and chromatin diversity of enhancers and their roles in different gene-regulatory programmes. We quantified enhancer activities along the entire human genome using STARR-seq6 in HCT116 cells, following the rapid degradation of eight cofactors. This analysis identified different types of enhancers with distinct cofactor requirements, sequences and chromatin properties. Some enhancers were insensitive to the depletion of the core Mediator subunit MED14 or the bromodomain protein BRD4 and regulated distinct transcriptional programmes. In particular, canonical Mediator7 seemed dispensable for P53-responsive enhancers, and MED14-depleted cells induced endogenous P53 target genes. Similarly, BRD4 was not required for the transcription of genes that bear CCAAT boxes and a TATA box (including histone genes and LTR12 retrotransposons) or for the induction of heat-shock genes. This categorization of enhancers through cofactor dependencies reveals distinct enhancer types that can bypass broadly utilized cofactors, which illustrates how alternative ways to activate transcription separate gene expression programmes and provide a conceptual framework to understand enhancer function and regulatory specificity.

Risk Factors for Repeat Keratoplasty After Endothelial Keratoplasty-An IRIS Registry Analysis.

PURPOSE: To assess risk factors for repeat keratoplasty after endothelial keratoplasty (EK). DESIGN: Retrospective cohort study. METHODS: EK procedures performed between 2013 and 2018 in the IRIS Registry (Intelligent Research in Sight) were identified. STUDY POPULATION: Patients aged 18 years and older who underwent EK. MAIN OUTCOME MEASURES: (1) Risk factors for repeat keratoplasty and (2) complication rates after EK. A Kaplan-Meier survival analysis was used to determine the probability of repeat keratoplasty. A multivariable shared frailty survival model was used to assess risk factors. RESULTS: A total of 59 344 procedures were identified in the registry, of which 30 600 EK procedures met the inclusion criteria for the analysis. The probability of repeat keratoplasty was 17.4% (95% CI 16.7-18.0) at 5 years. Risk factors for repeat keratoplasty include postoperative rebubbling procedure (HR 2.24, 95% CI 2.05-2.45), prior failed graft (HR 2.07, 95% CI 1.84-2.32) or bullous keratopathy (HR 1.47, 95% CI 1.33-1.61) vs Fuchs dystrophy as surgical indication; subsequent routine cataract surgery (HR 1.61, 95% CI 1.45-1.79), as well as subsequent (HR 1.53, 95% CI 1.39-1.69) and prior/concurrent (HR 1.23, 95% CI 1.11-1.36) glaucoma surgery or history of glaucoma (HR 1.24, 95% CI 1.14-1.35). Medicaid (HR 1.47, 95% CI 1.13-1.92), military/government (HR 1.29, 95% CI 1.03-1.60), Medicare Fee-for-Service (HR 1.17, 95% CI 1.05-1.31) or Medicare Managed (HR 1.17, 95% CI 1.01-1.36) insurances vs private insurance, as well as Black vs White race (HR 1.25, 95% CI 1.11-1.40) and smoking (HR 1.16, 95% CI 1.05-1.27) were also associated with an increased risk of undergoing repeat keratoplasty. CONCLUSIONS: Black race, government-based insurance plans, and smoking were identified as independent factors associated with repeat keratoplasty in addition to history of glaucoma, glaucoma surgery, and prior graft failure or bullous keratopathy as surgical indication.

Disparities in Visual Acuity Outcomes after Endothelial Keratoplasty: An Intelligent Research in Sight Registry Analysis.

PURPOSE: To assess risk factors for lack of vision improvement after endothelial keratoplasty (EK). DESIGN: Retrospective cohort study. PARTICIPANTS: Patients aged 18 years and older in the Intelligent Research in Sight (IRIS®) Registry who underwent EK surgery in the United States between 2013 and 2018. METHODS: Change in visual acuity (VA) relative to baseline were determined at 6 months and 1 year. A multivariable population-average marginal model estimated using generalized estimating equations adjusting for sociodemographic factors, baseline vision, surgical indication, ocular comorbidities, and postoperative complications was used to identify factors associated with worse VA outcomes. MAIN OUTCOME MEASURES: Visual acuity and lack of VA improvement at 1 year compared with preoperative status. RESULTS: A total of 30 600 EK procedures (N = 25 666 unique patients) were included in the analysis. Overall, VA improved from median logarithm of the minimum angle of resolution (logMAR) 0.54 (Snellen 20/69) (interquartile range [IQR] ± 0.70) preoperatively to median logMAR 0.40 (20/50) (IQR ± 0.36) at 6 months and median logMAR 0.30 (20/40) (IQR ± 0.36) at 1 year postoperatively. A total of 30.3% of the overall cohort, 29.8% of Fuchs' endothelial corneal dystrophy (FECD) subgroup, and 27.4% of the bullous keratopathy (BK) subgroup did not show visual improvement at 1 year postoperatively. In the FECD subgroup, older age (risk ratio [RR], 1.05 per 5-year increase, 95% confidence interval [CI], 1.03-1.07) and female sex (RR, 1.10, 95% CI, 1.04-1.16) were associated with VA worse than or equal to baseline at 1 year postoperatively. In both FECD and BK subgroups, eyes with higher baseline logMAR VA (per 0.1 unit increase in logMAR) were more likely to have visual improvement postoperatively (FECD: RR, 0.82, 95% CI, 0.81-0.84; BK: RR, 0.91, 95% CI, 0.91-0.92), whereas postoperative rebubbling (FECD: RR, 1.10, 95% CI, 1.02-1.19; BK: RR, 1.31, 95% CI, 1.17-1.48) and repeat keratoplasties (FECD: RR, 1.41, 95% CI, 1.32-1.52; BK: RR, 1.42, 95% CI, 1.28-1.57) were associated with higher risk of no VA improvement. CONCLUSIONS: In this large national cohort, postoperative rebubblings and repeat keratoplasties were identified as independent factors associated with worse VA outcomes after EK for both FECD and BK subgroups. Older age and female gender were associated with worse VA outcomes after EK in the FECD subgroup.

Stem cell induced inflammatory hypertrophy of the cauda equina.

Stem cell therapy can present clinicians with challenging clinical scenarios, as access to such treatments outpaces the research into their efficacy and safety due to the burgeoning trend of international travel to acquire stem cell therapy, or "stem cell tourism." Treatment of neurologic conditions remains an enticing potential application of stem cell therapy, often administered intrathecally. In response to such therapy, multiple adverse events have been described in the literature, including neoplasms, demyelinating disease, and seizures, among others. We present a case of symptomatic inflammatory cauda equina nerve root hypertrophy due to intrathecal stem cell infusion, representing a rare but significant complication.

A distinct core regulatory module enforces oncogene expression in KMT2A-rearranged leukemia.

Acute myeloid leukemia with KMT2A (MLL) rearrangements is characterized by specific patterns of gene expression and enhancer architecture, implying unique core transcriptional regulatory circuitry. Here, we identified the transcription factors MEF2D and IRF8 as selective transcriptional dependencies of KMT2A-rearranged AML, where MEF2D displays partially redundant functions with its paralog, MEF2C. Rapid transcription factor degradation followed by measurements of genome-wide transcription rates and superresolution microscopy revealed that MEF2D and IRF8 form a distinct core regulatory module with a narrow direct transcriptional program that includes activation of the key oncogenes MYC, HOXA9, and BCL2. Our study illustrates a mechanism of context-specific transcriptional addiction whereby a specific AML subclass depends on a highly specialized core regulatory module to directly enforce expression of common leukemia oncogenes.

Clinical care pathway for the evaluation of patients with suspected VITT after ChAdOx1 nCoV-19 vaccination.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adenoviral vector vaccination. In British Columbia (BC), Canada, a provincial clinical care pathway was developed to guide clinicians in evaluating for VITT among patients who present with thrombocytopenia or thrombosis symptoms within 4 to 28 days after adenoviral vector vaccine exposure. All patients had enzyme-linked immunosorbent assay (ELISA) testing for platelet factor 4 (PF4) antibodies, and all cases with positive PF4-ELISA or d-dimer levels ≥2.0 mg/L fibrinogen equivalent units (FEU) had further testing for platelet-activating PF4 antibodies using a modified serotonin release assay (SRA). Between 1 May and 30 June 2021, 37% of 68 patients investigated for VITT had thrombosis, but only 3 had VITT confirmed by PF4-ELISA and SRA. Platelet counts, d-dimer levels, and ELISA optical density values were significantly different between those with and without VITT. Three patients had thrombocytopenia and thrombosis with d-dimer levels >4.0 mg/L FEU but had negative PF4-ELISA and SRA results. Patients with VITT were treated successfully with IV immunoglobulin, nonheparin anticoagulants, and corticosteroids. Our pathway demonstrated that thrombosis is common among patients investigated for VITT and that PF4-ELISA testing is necessary to confirm VITT in those presenting with thrombosis and thrombocytopenia.

Immunological characterization of chicken tumor necrosis factor-α (TNF-α) using new sets of monoclonal antibodies specific for poultry TNF-α.

Tumor necrosis factor-α (TNF-α) is a type II transmembrane protein with either membrane-bound or soluble forms and is a prototypical member of the TNF superfamily. TNF-α is a pleiotropic cytokine associated with the regulation of systemic inflammation and host defense. Chicken TNF-α (chTNF-α) is a long-missed avian ortholog, and its immunological properties remain largely unknown compared to those of its mammalian counterparts. Here, we report the functional characterization and immunomodulatory properties of chTNF-α using a panel of newly developed anti-chTNF-α mouse monoclonal antibodies (mAbs). Using anti-chTNF-α mAbs, we determined the tissue expression of chTNF-α in lymphoid and non-lymphoid organs. A chTNF-α-specific antigen-capture sandwich ELISA was developed using compatible mAb partners by screening and validation of ten different mAbs. Employing 3G11 and 12G6 as capture and detection antibodies, respectively, the levels of native chTNF-α in the circulation of Clostridium perfringens, Eimeria, or dual C. perfringens/Eimeria-infected chickens were determined. Furthermore, intracellular expression of chTNF-α in primary immune cells or cell lines derived from chickens was validated by immunocytochemistry and flow cytometry assays using both 3G11 and 12G6 mAbs. Notably, both 3G11 and 12G6 neutralized chTNF-α-induced nitric oxide production in chicken HD11 cells in vitro. Collectively, our results enhance our understanding of the functional characteristics of chTNF-α, and these anti-chTNF-α mAbs will serve as valuable immune reagents to inform on inflammatory responses and disease pathogenesis in the fundamental and applied studies of avian species.