Hypoxic drive caused type 3 neovascularization in a preclinical model of exudative age-related macular degeneration.

Hypoxia associated with the high metabolic demand of rods has been implicated in the pathology of age-related macular degeneration (AMD), the most common cause of adult blindness in the developed world. The majority of AMD-associated severe vision loss cases are due to exudative AMD, characterized by neovascularization. To further investigate the causes and histopathology of exudative AMD, we conditionally induced hypoxia in a novel preclinical AMD model (Pde6gcreERT2/+;Vhl-/-) by targeting Vhl and used multimodal imaging and immunohistochemistry to track the development of hypoxia-induced neovascularization. In addition to developing a preclinical model that phenocopies exudative AMD, our studies revealed that the photoreceptor hypoxic response initiates and drives type 3 neovascularization, mainly in the outer retina. Activation of the VHL-HIF1a-VEGF-EPO pathway in the adult retina led to long-term neovascularization, retinal hemorrhages and compromised retinal layers. Our novel preclinical model would accelerate the testing of therapies that use metabolomic approaches to ameliorate AMD.

Surgical outcomes of two kinds of demineralized bone matrix putties/local autograft composites in instrumented posterolateral lumbar fusion.

BACKGROUND: This study aimed to assess the surgical outcomes of two kinds of demineralized bone matrix (DBM) putties/local autograft composites in instrumented posterolateral lumbar fusion (PLF). METHODS: Twenty-seven fusion segments of 19 patients, who underwent decompression and instrumented PLF for lumbar spinal stenosis or degenerative spondylolisthesis less than grade 1, were included in this study. The PLF mass consisted of different two kinds of DBMs (Grafton® and DBX®) and local autograft. Next, 7.5 cc of Grafton® DBM/local autograft composite was implanted on the left side, and the same amount of DBX® DBM/local autograft composite was implanted on the right side in the same patient. The PLF masses of 54 total sides (27 Grafton® sides and 27 DBX® sides) were assessed for fusion based on both flexion/extension lateral radiographs and computed tomography images at 12 and 24 months postoperatively. Clinical symptoms were also evaluated. RESULTS: At 12 months postoperatively, the fusion rates for the Grafton® and DBX® sides were 59.5 and 51.9%, respectively; the difference was not statistically significant (P = 0.425). At 24 months postoperatively, the fusion rates for the Grafton® and DBX® sides increased to 70.4 and 66.7%, respectively, but the difference was still not statistically significant (P = 0.574). Diabetes mellitus, smoking, and obesity (body mass index ≥25) negatively affected the fusion rate of both the Grafton® and DBX® sides. Visual analog scores for lower back pain and leg pain and Oswestry Disability Index were significantly improved after surgery (both, P < 0.01). No deep or superficial infections occurred postoperatively. No patients underwent revision surgery due to nonunion during follow-up. CONCLUSIONS: Our results suggest that two kinds of DBMs/local autograft composites might be considered as useful bone graft substitute in instrumented posterolateral fusion for lumbar spinal stenosis or degenerative spondylolisthesis less than grade 1.

The potential causal relationship between BMI, T1D, urolithiasis, and hydronephrosis in European ancestry: A Mendelian randomization analysis.

Body mass index (BMI), type 1 diabetes (T1D), urolithiasis, and hydronephrosis are interrelated. Our aim was to analyze their causal relationships at the genetic level. Mendelian randomization is an instrumental variable analysis method that follows Mendel genetic law of random allocation of parental alleles to offspring. In observational studies, genetic variants are used as instrumental variables to infer causal relationships between exposure factors and study outcomes. All the genome-wide association study data in our study were publicly available and from published genome-wide association studies, UK Biobank, and FinnGen. Random-effects inverse variance weighted was the primary analysis method, with R Egger, weighted median, and weighted mode as supplementary methods. We examined heterogeneity, horizontal pleiotropy, and the influence of individual single nucleotide polymorphisms on the analysis. We further explored the causal relationships between BMI, T1D, urolithiasis, and hydronephrosis, as well as the robustness of the analysis results. Inverse variance weighted results showed genetic causal relationships between BMI (P = .034, odds ratio [OR] 95% confidence interval [CI] = 1.273 [1.019-1.589]), T1D (P = .028, OR 95% CI = 0.921 [0.855-0.991]), urolithiasis (P < .001, OR 95% CI = 1.361 [1.175-1.576]), and hydronephrosis. Sensitivity analyses confirmed the accuracy and robustness of these findings. Our results support significant causal roles of BMI, T1D, and urolithiasis in hydronephrosis, potentially offering new intervention strategies for preventing its development.

Risk factor analysis for infection and bleeding after lateral decubitus percutaneous nephrolithotomy.

This study aimed to explore the risk factors for infection and bleeding after lateral decubitus percutaneous nephrolithotomy procedures to prevent their occurrence and improve surgical outcomes. A retrospective analysis was conducted on 356 patients who underwent lateral decubitus percutaneous nephrolithotomy for the treatment of kidney stones and upper ureteral stones from January 2015 to August 2022. Among them, 290 patients had complete clinical data. General clinical data, perioperative data, and stone characteristics were collected for each patient. Univariate and multivariate logistic regression analyses were performed to identify risk factors for infection and bleeding after lateral decubitus percutaneous nephrolithotomy. The postoperative infection rate after lateral decubitus percutaneous nephrolithotomy was 19.31%, and the postoperative bleeding rate was 12.07%. Independent risk factors for postoperative infection were multiple stones (P < .001), stone size (P < .001), and stone co-infection (P = .012). Independent risk factors for postoperative bleeding were multiple stones (P = .008) and stone size (P = .014). Multiple stones, stone size, and stone co-infection are independent risk factors for postoperative infection after lateral decubitus percutaneous nephrolithotomy. Multiple stones and stone size are independent risk factors for postoperative bleeding after lateral decubitus percutaneous nephrolithotomy.

Analysis of the Efficacy and Risk Factors for Failure of Balloon Dilation for Benign Ureteral Stricture.

This study aimed to investigate the efficacy of balloon dilation in ureteral stricture and to analyze the risk factors for the failure of balloon dilation, which will hopefully provide some reference for clinicians to develop treatment plans. We retrospectively analyzed 196 patients who underwent balloon dilation between January 2012 and August 2022, 127 of whom had complete baseline and follow-up data. General clinical data, perioperative data, balloon parameters at the time of surgery, and follow-up results were collected from the patients. Univariate and multivariate logistic regression analyses were performed for the risk factors for surgical failure in patients undergoing balloon dilatation. The success rates of balloon dilatation (n = 30) and balloon dilatation combined with endoureterotomy (n = 37) for lower ureteral stricture at 3 months, 6 months, and 1 year were 81.08%, 78.38%, and 78.38% and 90%, 90%, and 86.67%, respectively. The success rates of balloon dilation at 3 months, 6 months, and 1 year in patients with recurrent upper ureteral stricture after pyeloplasty (n = 15) and primary treatment (n = 30) were 73.33%, 60%, and 53.33% and 80%, 80%, and 73.33%, respectively. The success rates of surgery at 3 months, 6 months, and 1 year for patients with recurrence of lower ureteral stricture after ureteral reimplantation or endoureterotomy (n = 4) and primary treatment with balloon dilatation (n = 34) were 75%, 75%, and 75% and 85.29%, 79.41%, and 79.41%, respectively. Multivariate analysis of the failure of balloon dilation showed that balloon circumference and multiple ureteral strictures were risk factors for balloon dilation failure (OR = 0.143, 95% CI: 0.023-0.895, p = 0.038; OR = 1.221, 95% CI: 1.002-1.491, p = 0.05). Balloon dilation combined with endoureterotomy in lower ureteral stricture had a higher success rate than balloon dilation alone. The success rate of balloon dilation in the primary treatment of the upper and lower ureter was higher than that of balloon dilation in the secondary treatment after failed repair surgery. Balloon circumference and multiple ureteral strictures are risk factors for balloon dilation failure.