Citations

ImportanceDetermining spectacle-corrected visual acuity (VA) is essential when managing many ophthalmic diseases. If artificial intelligence (AI) evaluations of macular images estimated this VA from a fundus image, AI might provide spectacle-corrected VA without technician costs, reduce visit time, or facilitate home monitoring of VA from fundus images obtained outside of the clinic.ObjectiveTo estimate spectacle-corrected VA measured on a standard eye chart among patients with diabetic macular edema (DME) in clinical practice settings using previously validated AI algorithms evaluating best-corrected VA from fundus photographs in eyes with DME.Design, Setting, and ParticipantsRetrospective cross-sectional evaluation of deidentified fundus photographs matched to spectacle-corrected VA determined by technicians on eye charts among patients with a history of DME based on optical coherence tomography and at least 2 visits within 1 to 6 months of each other at a university-based clinic between January 2014 and December 2022. Data were analyzed from January 2023 to October 2024.ExposurePreviously validated AI algorithm evaluation of fundus photographs.Main Outcomes and MeasuresAI-determined VA mean absolute error (MAE) compared with actual spectacle-corrected VA.ResultsAmong 141 patients, the mean (SD) age was 63 (13) years, 71 (50%) were male, 2 (1%) were Asian, 42 (30%) were Black or African American, and 88 (63%) were White. Among 282 eyes at visit 1, 66 had nonproliferative diabetic retinopathy (NPDR) and DME, 38 had proliferative diabetic retinopathy (PDR) and DME, 101 had NPDR and no DME, and 77 had PDR and no DME. Among 564 images (282 eyes) at both initial and follow-up visits, MAE (SD) among eyes with NPDR, with or without center-involved DME (CI-DME), was 1.16 (1.00) lines on the eye chart for VA between 20/10 and 20/20 (67 images), and 1.44 (1.15) lines for between VA 20/25 and 20/80 (231 images). MAE (SD) among eyes with PDR, with or without CI-DME, was 1.92 (1.08) lines for VA between 20/10 and 20/20 (50 images), and 1.42 (0.97) lines for spectacle-corrected VA between 20/25 and 20/80 (150 images). Only 65 images had VA 20/100 or worse, precluding meaningful analyses.Conclusions and RelevanceIn this cross-sectional study, AI evaluation of fundus photographs among patients with DME and VA 20/80 or better estimated spectacle-corrected VA within approximately 1 to 1.5 lines of actual spectacle-corrected VA. These results support use of AI evaluation of fundus photographs to determine spectacle-corrected VA among patients with DME globally, beyond ophthalmology offices.

ABSTRACT Background and Objective Previously, the novel small molecule ISFP10 has been shown to inhibit fungal phosphoglucomutase (PGM) activity in Aspergillus fumigatus and Pneumocystis spp. With 50-fold selectivity over the human PGM molecule due to the presence of a unique yet conserved cysteine residue present in a number pathogenic fungal PGMs, use of this compound may provide a novel broad-spectrum approach to treating fungal infections. Accordingly, we sought to determine the tolerability in test animals receiving this compound, as well as the potential antifungal activity of ISFP10 on cultures of the common fungal pathogens Candida albicans and Candida glabrata . Methods C57BL6 mice received once daily intraperitoneal (IP) injections of 100 mL of vehicle control (DMSO) or ISFP10 at a concentration of 10 mg/kg. Body weights were recorded daily for 7 days of treatment. On the final day, mice were weighed and euthanized. Postmortem blood collection was conducted via cardiac puncture and distributed to EDTA and lithium heparin tubes for complete blood count (CBC) and comprehensive blood chemistry panels, respectively. Liver, kidney, and lung tissue were also harvested and placed in 10% formalin for H&E staining and blinded histopathologic scoring. Lung samples were further analyzed for proinflammatory cytokines using enzyme-linked immunosorbent assays (ELISA) and quantitative PCR (qPCR). Furthermore, ISPF10 was tested for antifungal activity via 8-hour growth curve analysis in a concentration-dependent fashion against Candida albicans and Candida glabrata . Results There was no significant difference in the daily or final body weights of the mice receiving 10 mg/kg of ISFP10 compared to those of the vehicle control group. Extracellular matrix (ECM) transcripts for IL-6 and TNFα were statistically similar via qPCR. ELISA results of proinflammatory cytokines for IL-6 was not significant whereas TNFα levels in lung tissue from the ISFP10 treatment group were significantly reduced, indicating a potential anti-inflammatory effect of ISFP10 at this dosage. Overall, blood chemistry and CBC analysis revealed no overall significant differences between the two groups, except for increased neutrophil counts and decreased potassium levels in samples collected from ISFP10 treated animals compared to the vehicle control group. These laboratory abnormalities were not of clinical significance to the test animals. Blinded histopathological examination revealed no abnormalities or evidence of critical organ toxicity from all groups. Inhibition of C. albicans and C. glabrata culture growth by ISFP10 was concentration-dependent in YPD liquid media containing the ISFP10 compared to vehicle control. Conclusions Our preliminary testing of ISFP10 revealed no inherent safety or toxicology concerns within the observed parameters. These data further support significant culture suppressive activity against C. albicans and C. glabrata . Taken together, these observations of ISFP10 further indicate that targeting PGM might be a novel and viable therapeutic strategy for serious fungal infections. Key points An inhibitor specific to fungal PGM enzymes, termed ISFP10, was generally well tolerated when administered via intraperitoneal (IP) injection in mice. ISFP10 displays antifungal activity in a concentration-dependent manner against C. albicans and C. glabrata .

Objective To analyze the use of electrical field imaging (EFI) in the detection of extracochlear electrodes in cochlear implants (CI) Study Design Retrospective cohort study Setting Tertiary academic medical center Methods EFI patterns from 6 recipients with extracochlear electrodes were compared with 10 recipients with all intracochlear electrodes to identify differences in EFI patterns between these two groups. For the extracochlear group, EFI patterns were analyzed using two methods: visual inspection and calculation of the average impedance difference (AID) between specific EFI curves. These results were then compared with information from CT and plain film imaging, surgical notes, and audiology tests to confirm the placement of the electrodes in each recipient. Results An average AID of 0.06 kΩ was calculated from the EFI patterns for recipients with complete electrode insertion, whereas an average AID of 0.15 kΩ was calculated from the EFI curves measured for the extracochlear electrodes. Visual analysis of the EFI impedance curves for extracochlear electrodes showed a distinct separation from those measured for intracochlear electrodes. Based on AID analysis and visual inspection the EFI, patterns were in close agreement with the number of extracochlear electrodes detected based on either imaging, intraoperative surgical note, or audiological findings. Conclusion EFI is a noninvasive, inexpensive, and time-efficient measurement that can be used to detect extracochlear electrodes and monitor electrode migration from the cochlea.

Abstract Background Despite advances in our understanding of the molecular underpinnings of meningioma progression and innovations in systemic and local treatments, recurrent meningiomas remain a substantial therapeutic challenge. The objective of this systematic review and meta-analysis is to provide a historical baseline, contemporary analysis, and propose a “rate of probable interest” to inform future clinical trial design and development on behalf of the Response Assessment in Neuro-Oncology meningioma group. Methods PubMed, ClinicalTrials.gov, and ASCOpubs databases were screened for clinical trials evaluating the activity of systemic therapies for adults with recurrent meningiomas. The pooled progression-free survival at 6-months and 1-year (PFS-6 and PFS-1 year) values were calculated using the random effects technique with I2 indices. Results The pooled PFS-6 and PFS-1 year rates for recurrent WHO grade 1 meningiomas were 43.6% (95% CI: 22.7-67.0%, I2 = 80%) and 21.7% (95% CI: 6.2-53.9%, I2 = 76%), and for grades 2-3 meningiomas, the PFS-6 was 38.0% (95% CI: 28.3-48.8%, I2 = 68%). In the targeted therapy group, PFS-6 and PFS-1 year rates stood at 62.0% (I2 = 58%) and 49.0% (I2 = 63%) for grade 1, while for grades 2-3 tumors, the PFS-6 rates with targeted therapy and immunotherapy were 42.1% (I² = 60%) and 46.0% (I² = 0%), respectively. The benchmarks were set at 67% and 54% for PFS-6 and PFS-1 year for grade 1 tumors, and PFS-6 of 49% for grades 2-3 tumors. Conclusions Several studies have reported outcomes in patients with recurrent meningiomas testing a variety of agents with modest, but variable and progressively increasing activity. In this context, we recommend new benchmarks for future trials to define efficacy of future investigational therapies.

Abstract Southeast Minnesota is home to a significant population of Anuak individuals who seek care within the Mayo Clinic Health Systems. The city of Austin, MN is home to a population numbering around 450 Anuak individuals who are seen at the Mayo Clinic Austin location as well as the Rochester main campus of Mayo Clinic. In total, more than 3000 Anuak individuals live in Minnesota in what is considered to be the largest Anuak population outside of East Africa. For pediatric patients with SCD, 15 of 20 (75%) are Anuak. The majority of these patients have severe SCD with chronic anemia, frequent pain crises, cardiac ventricular enlargement, acute chest pain, and multiple hospital admissions. The objective of this review is to understand what is known about SCD, the severity of phenotype, and outcomes in the published literature regarding this special population. A scoping review was conducted using primarily OVID databases. Only 2 studies met established criteria. Unfortunately, both sources of literature were dated and not consistent with current trends. Despite communicating with colleagues in Ethiopia, there does not exist accurate or robust data about the incidence or prevalence of SCD among the Anuak people. The local Anuak diaspora in Southeast Minnesota likely represents the best current data and representation in this patient population. There is a need for further research regarding SCD outcomes in this special population.

ABSTRACT Background Multiple outpatient therapies have been developed for COVID‐19 in high‐risk individuals, but solid organ transplant (SOT) recipients were not well represented in controlled clinical trials. To date, few comparative studies have evaluated outcomes between outpatient therapies in this population. Methods We performed a retrospective cohort study using de‐identified administrative claims data from OptumLabs Data Warehouse. Patients were included if they were age ≥ 18 years, diagnosed with COVID‐19 between January 2022 and December 2023, and underwent SOT prior to COVID‐19. The primary outcome was 30‐day hospitalization. Stabilized inverse probability of treatment weighting was used to account for potential confounding variables. Results 4192 SOT recipients with COVID‐19 were identified. 1403 received an outpatient COVID‐19 therapy, including anti‐spike monoclonal antibodies ( N = 748, 53.3%), molnupiravir ( N = 327, 23.3%), ritonavir‐boosted nirmatrelvir ( N = 217, 15.5%), or remdesivir ( N = 141, 10.0%). In weighted analysis compared to no treatment, anti‐spike monoclonal antibodies (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.28–0.55; p < 0.001), molnupiravir (HR 0.56, 95% CI 0.36–0.89; p = 0.013), and nirmatrelvir (HR 0.47, 95% CI 0.25–0.89; p = 0.020) were associated with reduced hospitalization risk, while remdesivir (HR 1.00, 95% CI 0.50–1.98; p = 0.992) was not. Hospitalization rates were similar between the treatment agents, apart from remdesivir showing a higher risk compared to anti‐spike monoclonal antibodies. Conclusions Outpatient COVID‐19 therapies were largely associated with improved outcomes among SOT recipients. These treatment agents showed similar rates of 30‐day hospitalization, except for remdesivir. The choice of outpatient COVID‐19 therapy in SOT recipients should primarily account for patients’ individual circumstances and drug‐drug interactions rather than differential therapeutic efficacy. image

Abstract Inotuzumab ozogamicin (InO) is an antibody-calicheamicin conjugate with striking efficacy in B-cell acute lymphoblastic leukemia (B-ALL). However, there is wide interpatient variability in treatment response, and the genetic basis of this variation remains largely unknown. Using a genome-wide CRISPR screen, we discovered that the loss of DNA nucleotidylexotransferase (DNTT) is a primary driver of InO resistance. Mechanistically, the downregulation of DNTT attenuated InO–induced DNA damage response, cell cycle arrest, and mitochondrial apoptotic priming, thereby ultimately leading to leukemia resistance to InO. Ex vivo leukemia InO sensitivity was highly associated with DNTT expression in ALL blasts with substantial intraleukemia heterogeneity as revealed by single-cell RNA sequencing. Among patients with B-ALL enrolled in the Children's Oncology Group trial AALL1621, we observed consistent DNTT downregulation in residual blasts following InO treatment. The selection of DNTT-low blasts by InO therapy was also recapitulated in vivo using patient-derived xenograft models. Collectively, our data indicate that DNTT is a key regulator of calicheamicin response in leukemia and thus a potential biomarker for individualizing InO therapy in B-ALL.

Abstract Background Chronic kidney disease (CKD) increases cardiac arrest (CA) risk because of renal and cardiovascular interactions. Methods Using Centers for Disease Control and Prevention (CDC) data from 1999 to 2020, we analyzed CKD‐related CA mortality and the impact of social vulnerability index (SVI). Results We identified 336 494 CKD‐related CA deaths, with stable age‐adjusted mortality rates over time. Disparities were observed across gender, racial/ethnic, and geographic subpopulations, with higher mortality among males, Hispanic and non‐Hispanic Black populations, and those in urban and Western regions. Higher SVI correlated with increased mortality. Conclusions CKD‐related CA mortality rates are stable, with disparities across demographics; higher SVI correlates with increased mortality, highlighting needed interventions.