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Background: To clarify the risk of adverse ocular events following influenza vaccination. Methods: This self-controlled case series study used a claims database linked to vaccination records of a large city in Japan between April 2014 and September 2021. Individuals aged ≥ 65 years who developed adverse ocular events during the follow-up period were included. The exposure was influenza vaccination. The primary outcome was defined as the occurrence of at least one of the following five eye diseases: uveitis, scleritis, retinal vein occlusion, retinal artery occlusion, or optic neuritis. Conditional Poisson regression was used to estimate the within-subject incidence rate ratio of ocular adverse events during the risk period (0–56 days after vaccination) compared to the control period. Results: A total of 4,527 cases were eligible for the study (median age, 74 years; male, 42%). The incidence rate ratio for the outcome during the risk period was 0.99 (95% confidence interval, 0.87 to 1.14). No increased risk was observed for individual components of the outcome either; the incidence rate ratio was 0.94 (0.78 to 1.13) for uveitis, 1.17 (0.86 to 1.59) for scleritis, 0.98 (0.76 to 1.27) for retinal vein occlusion, 0.89 (0.42 to 1.87) for retinal artery occlusion, and 0.87 (0.44 to 1.70) for optic neuritis. Conclusions: This self-controlled case series showed no apparent increase in the risk of adverse ocular events after influenza vaccination among older adults. These results mitigate the concerns of older adults who may hesitate to receive influenza vaccination for fear of adverse ocular events. Abbreviation: HR = hazard ratio; CI = confidence interval; RVO = retinal vein occlusion; SCCS = self-controlled case series [ABSTRACT FROM AUTHOR]

Study Design: A retrospective cohort study using the Kaplan-Meier method with propensity-score matching. Purpose: To evaluate whether the presence of prevalent morphometric vertebral fractures (VFs) poses a risk for subsequent clinical VFs after short-fusion surgery in women aged ≥60 years with degenerative spondylolisthesis. Overview of Literature: VFs are common osteoporotic fractures and are associated with a low quality of life. Subsequent VFs are a complication of instrumented fusion in patients with degenerative lumbar disorders. Thus, risk factors for subsequent VFs after fusion surgery must be analyzed. Population-based studies have suggested that prevalent morphometric VFs led to a higher incidence of subsequent VFs in postmenopausal women; however, no studies have investigated whether prevalent morphometric VFs are a risk factor for subsequent VFs after fusion surgery in patients with degenerative spondylolisthesis. Methods: The study enrolled a total of 237 older female patients: 50 and 187 patients had prevalent morphometric VFs (VF [+] group) and nonprevalent morphometric VFs (VF [−] group), respectively. The time to subsequent clinical VFs after fusion surgery was compared between the two groups using the Kaplan-Meier method. Moreover, 40 and 80 patients in the VF (+) and VF (−) groups, respectively, were analyzed and matched by propensity scores for age, follow-up duration, surgical procedure, number of fused segments, body mass index, and number of patients treated for osteoporosis. Results: Kaplan-Meier analysis indicated that the VF (+) group had a higher incidence of subsequent clinical VFs than the VF (−) group, and Cox regression analysis showed that the presence of prevalent morphometric VFs was an independent risk factor for subsequent clinical VFs before matching. Kaplan-Meier analysis demonstrated comparable results after matching. Conclusions: The presence of prevalent morphometric VFs may be a risk factor for subsequent clinical VFs in older women with degenerative spondylolisthesis who underwent short-fusion surgery. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective case-control propensity score-matching study. Purpose: This study aimed to longitudinally evaluate whether preoperative ligamentous stenosis at the spondylolisthetic segments could affect the incidence of symptomatic adjacent canal stenosis following one-segment fusion surgery. Overview of Literature: Several risk factors for symptomatic adjacent canal stenosis following fusion surgery have been assessed. Patients with lumbar canal stenosis mainly due to ligamentum flavum (LF) hypertrophy (ligamentous stenosis) also have LF hypertrophy in other segments. Methods: In total, 76 patients participated in this case-control study (neurologically symptomatic adjacent canal stenosis, n=33; neurologically asymptomatic cases at follow-up, n=43). Their risk factors during surgery and magnetic resonance (MR) images before the surgery and at follow-up were evaluated. Data from the two groups (n=25 each) were matched using propensity scores for age, sex, time to MR imaging at follow-up, surgical procedure, and LF hypertrophy in adjacent segments before the surgery and analyzed. Results: Compared with the asymptomatic group, the symptomatic adjacent canal stenosis group had a significantly larger LF area/spinal canal area in the spondylolisthetic segments before the surgery. During the follow-up periods (in months), they had a larger LF area/spinal canal area in the adjacent segments: the two values were significantly correlated. The sensitivity, specificity, and positive and negative predictive values for determining symptomatic adjacent canal stenosis were high compared with on the cutoff value for the LF area/spinal canal area at the spondylolisthetic segments before the surgery. These results were the same after matching. Conclusions: Symptomatic adjacent canal stenosis is mainly caused by LF hypertrophy. Ligamentous stenosis at the spondylolisthetic segments before fusion surgery might be strongly associated with symptomatic adjacent canal stenosis at follow-up. [ABSTRACT FROM AUTHOR]

When estimating the causal effects of time-varying treatments on survival in nested case-control (NCC) studies, marginal structural Cox models (Cox-MSMs) with inverse probability weights (IPWs) are a natural approach. However, calculating IPWs from the cases and controls is difficult because they are not random samples from the full cohort, and the number of subjects may be insufficient for calculation. To overcome these difficulties, we propose a method for calculating IPWs to fit Cox-MSMs to NCC sampling data. We estimate the IPWs using a pseudo-likelihood estimation method with an inverse probability of sampling weight using NCC samples, and additional samples of subjects who experience treatment changes and subjects whose follow-up is censored are required to calculate the weights. Our method only requires covariate histories for the samples. The confidence intervals are calculated from the robust variance estimator for the NCC sampling data. We also derive the asymptotic properties of the estimator of Cox-MSM under NCC sampling. The proposed methods will allow researchers to apply several case-control matching methods to improve statistical efficiency. A simulation study was conducted to evaluate the finite sample performance of the proposed method. We also applied our method to a motivating pharmacoepidemiological study examining the effect of statins on the incidence of coronary heart disease. The proposed method may be useful for estimating the causal effects of time-varying treatments in NCC studies. [ABSTRACT FROM AUTHOR]

During periods of fasting, the body undergoes a metabolic shift from carbohydrate utilization to the use of fats and ketones as an energy source, as well as the inhibition of de novo lipogenesis and the initiation of gluconeogenesis in the liver. The transcription factor sterol regulatory element‐binding protein‐1 (SREBP‐1), which plays a critical role in the regulation of lipogenesis, is suppressed during fasting, resulting in the suppression of hepatic lipogenesis. We previously demonstrated that the interaction of fasting‐induced Kruppel‐like factor 15 (KLF15) with liver X receptor serves as the essential mechanism for the nutritional regulation of SREBP‐1 expression. However, the underlying mechanisms of KLF15 induction during fasting remain unclear. In this study, we show that the glucocorticoid receptor (GR) regulates the hepatic expression of KLF15 and, subsequently, lipogenesis through the KLF15‐SREBP‐1 pathway during fasting. KLF15 is necessary for the suppression of SREBP‐1 by GR, as demonstrated through experiments using KLF15 knockout mice. Additionally, we show that GR is involved in the fasting response, with heightened binding to the KLF15 enhancer. It has been widely known that the hypothalamic–pituitary–adrenal (HPA) axis regulates the secretion of glucocorticoids and plays a significant role in the metabolic response to undernutrition. These findings demonstrate the importance of the HPA‐axis‐regulated GR‐KLF15 pathway in the regulation of lipid metabolism in the liver during fasting. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a progressive disorder denoted by hyperglycemia and impaired insulin secretion. Although a decrease in β-cell function and mass is a well-known trigger for diabetes, the comprehensive mechanism is still unidentified. Here, we performed single-cell RNA sequencing of pancreatic islets from prediabetic and diabetic db/db mice, an animal model of type 2 diabetes. We discovered a diabetes-specific transcriptome landscape of endocrine and nonendocrine cell types with subpopulations of β- and α-cells. We recognized a new prediabetic gene, Anxa10, that was induced by and regulated Ca2+ influx from metabolic stresses. Anxa10-overexpressed β-cells displayed suppression of glucose-stimulated intracellular Ca2+ elevation and potassium-induced insulin secretion. Pseudotime analysis of β-cells predicted that this Ca2+-surge responder cluster would proceed to mitochondria dysfunction and endoplasmic reticulum stress. Other trajectories comprised dedifferentiation and transdifferentiation, emphasizing acinar-like cells in diabetic islets. Altogether, our data provide a new insight into Ca2+ allostasis and β-cell failure processes. Article Highlights: The transcriptome of single-islet cells from healthy, prediabetic, and diabetic mice was studied. Distinct β-cell heterogeneity and islet cell-cell network in prediabetes and diabetes were found. A new prediabetic β-cell marker, Anxa10, regulates intracellular Ca2+ and insulin secretion. Diabetes triggers β-cell to acinar cell transdifferentiation. [ABSTRACT FROM AUTHOR]