Citations

ABSTRACT Purpose The natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) remains understudied, with limited long‐term data from large cohorts inclusive of both salvage radiotherapy (SRT)‐treated and untreated patients. Herein, we sought to evaluate the outcomes of patients with BCR and the impact of SRT on disease progression. Materials and Methods Patients undergoing RP who developed BCR (PSA ≥ 0.20 ng/mL) were included. Patients with BCR treated with SRT were compared to untreated patients using risk‐set matching with time‐dependent propensity scores. The primary outcome was metastases, analyzed using Kaplan–Meier and Cox models. The number needed to treat (NNT) with SRT to prevent progression was derived at 5 and 15 years. Results Among 6881 patients with BCR, 2109 received SRT. At a median follow‐up of 10.2 years, 1147 patients developed metastases. The median PSA at the time of SRT was 0.50 ng/mL. After 1:1 propensity score matching (2109 patients per cohort), SRT significantly reduced the risk of metastases at 5 (12.7% vs. 19.3%, p < 0.0001) and 15 years (28.6% vs. 31.5%, p < 0.001). On multivariable analysis, SRT independently reduced metastasis risk (HR 0.75, 95% CI 0.63–0.90, p = 0.002), translating to NNT of 23 and 15 at 5 and 15 years, respectively. Interaction analyses between SRT and nodal status ( p = 0.04) showed greater metastasis risk reduction in pN+ (HR 0.41, 95% CI 0.22–0.77, p = 0.005) compared to pN− disease (HR 0.81, 95% CI 0.67–0.97, p = 0.02). Conclusions Most patients with BCR post‐RP do not progress to metastasis. For those who do progress, SRT inarguably improves the oncologic outcomes in the BCR setting. However, careful patient selection and shared decision making should be encouraged in order to limit overtreatment and side effects.

INTRODUCTION: Many patients with chronic pouchitis and Crohn's-like disease of the pouch (CLDP) are treated with biologics; however, the comparative effectiveness of advanced therapies in this population has not been systematically evaluated. We sought to compare the effectiveness of antitumor necrosis factor α (anti-TNF) therapies and ustekinumab in patients with chronic inflammatory conditions of the pouch. METHODS: We conducted a prospective, multicenter, cohort study. We included patients with chronic pouchitis and CLDP initiating treatment with anti-TNF therapies or ustekinumab. The primary outcome was clinical remission at 6 months after induction. We also evaluated clinical remission at 6 months among patients with chronic pouchitis and CLDP separately. RESULTS: Among 132 patients, 106 (80%) had a diagnosis of CLDP and 82 (62%) initiated therapy with ustekinumab. A significantly higher proportion of patients with CLDP treated with ustekinumab were in clinical remission at 6 months as compared with patients treated with anti-TNF therapy (62% vs 40%, P = 0.027); however, there was no significant difference among patients with chronic pouchitis ( P = 0.946). There was no independent statistical significance in the odds of remission at 6 months among patients with CLDP among patients receiving ustekinumab compared with anti-TNF therapy (adjusted odds ratio 1.91, 95% confidence interval 0.69–5.30) after adjusting for presence of a fistula, number of preoperative advanced therapies, and number of advanced therapies after IPAA. DISCUSSION: These data suggest the potential benefit of ustekinumab in patients with CLDP and should prompt future novel effectiveness evaluations in this population.

OBJECTIVE In many individuals, type 2 diabetes (T2D) remains poorly controlled despite taking multiple glucose-lowering therapies. Several studies have demonstrated that endogenous hypercortisolism is prevalent among these individuals. We tested whether cortisol-directed therapy improves their glycemic control. RESEARCH DESIGN AND METHODS In this prospective, multicenter, double-blind study, 136 individuals with T2D (hemoglobin A1c [HbA1c] 7.5%–11.5% [58–102 mmol/mol] on multiple medications) and hypercortisolism (by dexamethasone suppression test) were randomized 2:1 to the glucocorticoid receptor antagonist mifepristone (300–900 mg once daily; n = 91) or placebo (n = 45) for 24 weeks, with stratification by presence/absence of an adrenal imaging abnormality. The primary end point was the change in HbA1c. Secondary end points included changes in glucose-lowering medications, weight, and waist circumference and safety. RESULTS Mean baseline HbA1c in the study cohort was 8.55% (69.9 mmol/mol). At 24 weeks, the least squares mean (LSM) difference from placebo in HbA1c was −1.32% (95% CI −1.81 to −0.83; P &lt; 0.001). Participants receiving mifepristone experienced reductions in body weight and waist circumference (placebo-adjusted LSM differences of −5.12 kg [95% CI −8.20 to −2.03] and −5.1 cm [−8.23 to −1.99], respectively). Of participants on mifepristone, 46% discontinued therapy, compared with 18% on placebo. Adverse events with mifepristone (&gt;10% of participants) included hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea, and dizziness, consistent with mifepristone’s known tolerability profile. Increases in blood pressure also occurred. CONCLUSIONS In individuals with inadequately controlled T2D and hypercortisolism, cortisol-directed medical therapy with mifepristone reduced HbA1c, with a manageable tolerability profile.

Study Design: Single-center retrospective cohort study. Objective: To determine if the 4-rod construct (4RC) is protective against the occurrence of rod fractures when compared with the 3-rod construct (3RC) in adult spinal deformity (ASD) patients with long fusions to the sacrum. Summary of Background Data: Past studies have explored the different outcomes in subjects with dual-rod versus multirod constructs. There is a lack of literature distinguishing the ramifications of 3RC versus 4RC, particularly in the prevalence of rod fractures and rod fractures requiring subsequent revision surgery as a result of pseudarthrosis. Methods: ASD patients undergoing long instrumented fusions to the sacrum were dichotomized between the 3RC and 4RC cohorts. Outcomes of interest include the occurrence of rod fractures (RFs) and RFs requiring revision (RFR). Two-tailed independent-sample t test with Welch's correction and χ 2 /Fisher exact test were used for continuous and categorical variables, respectively. Multivariable logistic regression analysis was performed to assess whether the 4RC is protective against rod fractures when compared with the 3RC. Results: One hundred forty-five patients with a minimum 2-year follow-up were included (3RC=57, 4RC=88). Four RC had a greater body mass index (BMI) ( P =0.002), longer operating room (OR) time ( P =0.002), greater estimated blood loss (EBL) ( P =0.002), total instrumented levels (TIL) ( P =0.028), and more 3-column osteotomies (3COs) performed ( P =0.028). Four RC had greater baseline coronal vertical axis (CVA) (28.2±24.9 vs. 18.5±16.9 mm, P =0.006) and sagittal vertical axis (SVA) (55.1±64.8 vs. 30.4±41.8 mm, P =0.006). Three RC had a greater rate of RF (28.1% vs. 14.8%, P =0.0506) and RFR (14.9% vs. 10.2%, P =0.486) when compared with 4RC, but these findings were not statistically significant. After controlling for BMI, the use of 3-column osteotomies, total instrumented levels, change in coronal alignment (∆CVA), change in sagittal alignment (∆SVA), use of bone morphogenetic protein, and number of interbody fusions, 3RC was associated with 4.93× greater odds of experiencing RFs ( P =0.0078). However, significance fell short when adjusting for the occurrence of RFR [OR=2.58 (0.60–11.19), P =0.2067]. Conclusion: ASD patients having long fusions to the sacrum with 4RC across the lumbosacral junction are shown to be at lesser risk of developing rod fractures but not revision surgery as compared with 3RC at 2-year follow-up.

Abstract Professor Albert J. Rhoton Jr., MD, is renowned for his groundbreaking dissections, marking a monumental achievement in the field of neuroanatomy. Alongside his anatomical contributions, he also passed on his knowledge and skills to numerous fellows, leaving behind a profound legacy. Despite the widespread recognition of his influence, little quantitative work has been done to characterize the scholarly impact of his alumni. Data were collected on Rhoton fellows, including fellowship years, country of origin, current institutions, and titles, practice settings, and leadership roles. Scholarly productivity was evaluated by assessing publication counts, including publications before and after the fellowship, and publications focused on surgical anatomy. Additionally, H-indices and citation counts were recorded. Other variables analyzed included ownership of a surgical anatomy laboratory, and participation in organizing hands-on courses. We analyzed 118 alumni from diverse countries. There was a significant increase in publication output following the fellowship, with publications rising from an average of 7 to 76 (p < 0.001). Fellows from high-income countries had higher research productivity than those from middle-income countries, with greater average H-index (p = 0.003), publication count (p = 0.01), and citation score (p = 0.003). Overall, 65% of fellows pursued academic practice, with 18% owning a laboratory and 30% involved in hands-on courses. Dr. Rhoton's mentorship has shaped a generation of neurosurgeons who continue his legacy. His fellows have established careers worldwide, leading in academia, professional organizations, and surgical training. Their global impact underscores the lasting value of structured mentorship in neurosurgery.

Abstract Microglia are resident immune cells critical in maintaining brain homeostasis via their surveillance and phagocytosis function. Under disease contexts such as seizures and epilepsy, microglial phagocytic signalling is activated in response to both inflammatory and non‐inflammatory cell death. This process involves a range of well‐characterized ‘find me’ and ‘eat me’ signals, phagocytic receptors, and less well‐characterized intracellular signalling pathways. In addition, epigenetic and transcriptional regulators orchestrate microglial responses to seizures, including the integration of phagocytic and inflammatory pathways. Interestingly, although inhibiting phagocytosis has been shown to improve neuronal survival and cognitive performance after seizures, it paradoxically increases the risk of developing spontaneous recurrent seizures. Reconciling these dual effects requires a deeper understanding the spatiotemporal dynamics of microglial phagocytosis. The objective of this review is to examine the mechanisms and impact of microglial phagocytosis in the context of epilepsy and to highlight unresolved questions that warrant further investigation in this emerging field. image

ObjectivesAchalasia is an esophageal motility disorder that impairs quality of life and is often missed (20–50%) on endoscopy. A newly developed computer‐aided detection (CAD) software has shown high accuracy for achalasia diagnosis in preclinical settings. However, its benefit in a clinical setting remains unclear.MethodsBetween February and August 2023, 83 endoscopists from 27 centers assessed 50 randomized endoscopic videos (25 achalasia, 25 nonachalasia) without and with CAD. Endoscopists assessed videos without CAD, then with CAD after 2 months. The primary end‐point was improvement in sensitivity for nonexperienced endoscopists (no endoscopic experience of achalasia). Sensitivity, specificity, and accuracy with and without CAD were compared using the McNemar test.ResultsSensitivity for diagnosing achalasia increased significantly with CAD, rising from 74.2% (95% confidence interval [CI] 72.2–76.0%) to 91.2% (95% CI 89.9–92.4%) for all readers, showing a difference of 17.1% (95% CI 15.1–19.0%). Specifically, sensitivity improved from 66.9% (95% CI 63.6–70.0%) to 91.9% (95% CI 89.9–93.6%) among nonexperienced endoscopists, resulting in a difference of 25.0% (95% CI 21.7–28.4%), and from 79.5% (95% CI 77.1–81.8%) to 90.8% (95% CI 89.0–92.3%) among experienced endoscopists (endoscopic experience of at least one achalasia case), with a difference of 11.3% (95% CI 8.9–13.6%). Accuracy and specificity improved significantly with CAD assistance, regardless of reader's experience.ConclusionCAD improves achalasia detection by 17%, confirming preclinical results. The benefit was higher for nonexperienced endoscopists. CAD assistance may lead to prompt and effective treatment, minimizing the risk of false‐negative diagnosis in clinical practice.Trial registrationThis study was registered in the University Hospital Medical Information Network Clinical Trial Registry (https://www.umin.ac.jp/ctr/) number: UMIN000053047.