Citations

Importance Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined. Objective To develop consensus best practices for delivering NT to patients with localized PDAC. Design, Setting, and Participants This study used a modified Delphi approach consisting of 2 rounds of voting, and a series of virtual conferences (from October to December 2023) to reach expert consensus on candidate best practice statements generated from a systematic review of the literature and expert opinion. An interdisciplinary panel was formed including 47 North American experts from surgical, medical, and radiation oncology, radiology, pathology, gastroenterology, integrative oncology, anesthesia, pharmacy, nursing, cancer care delivery research, and nutrition as well as patient and caregiver stakeholders. Main Outcome and Measures Statements that reached 75% agreement or greater were included in final consensus statements. Results Of the 47 participating panel members, 27 (57.64%) were male, and the mean (SD) age was 47.6 (8.2) years. Physicians reported completing training a mean (SD) 14.6 (8.6) years prior and seeing a mean (SD) 110.6 (38.4) patients with PDAC annually; 35 (77.7%) were in academic practice. Final consensus was reached on 82 best practices for delivering NT. Of these, 38 statements focused on pre-NT practices, including diagnosis and staging (n = 15), evaluation and optimization (n = 20), and decision-making (n = 3); 29 statements defined best practices during NT, including initiation (n = 3), delivery of therapy (n = 8), restaging practices (n = 12), and management of complications during NT (n = 6); and 15 best practices were identified to guide treatment post-NT, focusing on surgery (n = 7), pathology (n = 4), and follow-up (n = 3). Conclusions Using a modified Delphi consensus technique, best practice guidelines were developed focusing on the optimal standards for delivering NT to patients with localized PDAC. Given the prognostic importance of completing multimodality therapy, efforts to standardize and optimize the delivery of NT represent an immediate opportunity to decrease care variation and improve outcomes for patients with PDAC. Future research should focus on validating and implementing best practice standards into clinical practice.

Abstract Semaglutide (Smg), a GLP‐1 receptor agonist (GLP‐1RA), shows renal protective effects in patients with diabetic kidney disease (DKD). However, the exact underlying mechanism remains elusive. This study employs transcriptome sequencing and identifies β ‐Klotho (KLB) as the critical target responsible for the role of Smg in kidney protection. Smg treatment alleviates diabetic kidney injury by inhibiting ferroptosis in patients, animal models, and HK‐2 cells. Notably, Smg treatment significantly increases the mRNA expression of KLB through the activation of the cyclic adenosine monophosphate (cAMP) signaling pathway, specifically through the phosphorylation of protein kinase A (PKA) and cAMP‐response element‐binding protein (CREB). Subsequently, the adenosine monophosphate‐activated protein kinase (AMPK) signaling pathway is activated, reprograming the key metabolic processes of ferroptosis such as iron metabolism, fatty acid synthesis, and the antioxidant response against lipid peroxidation. Suppression of ferroptosis by Smg further attenuates renal inflammation and fibrosis. This work highlights the potential of GLP‐1RAs and KLB targeting as promising therapeutic approaches for DKD management.

Background/Objectives: Spinal astrocytomas (SA) represent 30–40% of all intramedullary spinal cord tumors (IMSCTs) and present significant clinical challenges due to their aggressive behavior and potential for recurrence. We aimed to pool the evidence on SA and investigate predictors of regrowth or recurrence after surgical resection. Methods: A systematic review and meta-analysis were conducted on peer-reviewed human studies from several databases covering the field of SA. Data were collected including sex, age, tumor location, extent of resection, histopathological diagnosis, and adjuvant therapy to identify predictors of SA recurrence. Recurrence was defined as failure of local tumor control or regrowth after treatment. Results: A total of 53 studies with 1365 patients were included in the meta-analysis. A postoperative deterioration in neurological outcomes, as assessed by the modified McCormick scale, was noted in most of the patients. The overall recurrence rate amounted to 41%. On meta-analysis, high-grade WHO tumors were associated with higher odds of recurrence (OR = 2.65; 95% CI: 1.87, 3.76; p = 0.001). Similarly, GTR was associated with lower odds of recurrence compared to STR (OR = 0.33; 95% CI: 0.18, 0.60; p = 0.0003). Sex (p = 0.5848) and tumor location (p = 0.3693) did not show any significant differences in the odds of recurrence. Intraoperative neurophysiological monitoring was described in 8 studies and adjuvant radiotherapy in 41 studies. Conclusions: The results highlight the significant importance of tumor grade and extent of resection in patient prognosis. The role of adjuvant radiotherapy remains unclear, with most studies suggesting no differences in outcomes, with limitations due to potential confounders.

ABSTRACTObjectiveAlcohol‐related liver disease (ALD) has emerged as a significant public health concern, particularly among younger populations. ALD remains the leading cause of alcohol‐attributable deaths. This study aims to forecast ALD mortality trends up to 2030, focusing on individuals under 55 years.MethodsWe utilized data from the CDC WONDER database (1999–2022) to examine ALD‐related deaths, identified by ICD‐10 codes (K70.0–K70.9). Crude mortality rates (CMRs) per 100 000 were analyzed and temporal trends were assessed using annual and average annual percent changes (APC/AAPC) with empirical quantile confidence intervals. An Autoregressive Integrated Moving Average (ARIMA) model was employed to project mortality rates until 2030, validated through time series cross‐validation.ResultsFrom 1999 to 2022, there were 181 862 ALD‐related deaths among individuals under 55, with mortality rates increasing from 3.9 per 100 000 in 1999 to 9.7 per 100 000 in 2022 (AAPC 4.66%, 95% CI: 3.90%–5.86%). Projections suggest rates will continue to rise, reaching 14.4 per 100 000 by 2030. From 1999 to 2022, the 25–34 age group experienced the highest increase, with an AAPC of 10.27% (95% CI: 9.19%–11.35%), while the 35–44 and 45–54 age groups showed more moderate increases, with AAPCs of 5.03% and 4.38%, respectively. Projections indicate an AAPC of 3.86% for ages 25–34, 3.90% for ages 35–44, and 6.17% for ages 45–54 by 2030.ConclusionForecasts indicate a continued rise in ALD mortality among individuals under 55, necessitating immediate public health strategies to mitigate this trend.

Objective To analyze cases of medial migration of vestibular schwannomas to propose an underlying mechanism. Study Design Retrospective chart review. Patients Ten patients from one institution with sporadic vestibular schwannomas that demonstrated medial migration toward the cerebellopontine angle on serial imaging were reviewed. Interventions Among the 10 patients studied, 8 patients underwent stereotactic radiosurgery and 2 were managed with wait-and-scan. All serial imaging was analyzed throughout follow-up. Main Outcome Measures Volumetric and linear measurements were used to assess vestibular schwannoma growth. The fundal fluid cap length was measured from the most lateral end of the neoplasm within the internal auditory canal to the medial end of the cochlea. Pure tone averages of 0.5, 1, 2, and 3 kHz, word recognition scores, and AAO-HNS hearing class were used to assess levels of hearing loss per patient. Results Tumor growth exhibited a positive correlation with medial migration. Of the 10 patients studied, 9 exhibited tumor volume growth from initial to most recent imaging. Median changes in tumor volumes and fundal fluid cap lengths from initial diagnosis to the most recent imaging regardless of intervention were 130 mm3 (range 1,400–2,970) and 2.8 mm (range 1.8–6.0), respectively. Migration was noted in 4 patients prior to any intervention, in 4 patients postradiosurgery, and in 2 patients before and after radiosurgery. Therefore, half of the tumors studied migrated before an intervention and half migrated postradiosurgery. No correlation of migration and hearing decline was observed. Conclusion Medial migration of vestibular schwannoma is associated with an increase in tumor volume, supporting a “tumor squeeze” mechanism within a conical internal auditory canal toward the wider porus acusticus and cerebellopontine angle.

Blood flow restriction (BFR) is a popular resistance exercise technique purported to increase metabolic stress and augment training adaptations over time. However, short-term use may lead to acute neuromuscular fatigue and higher exertion ratings. Objective: The purpose of the current study was to examine acute physiological responses to low-load resistance exercise utilizing BFR compared to higher-load, non-BFR resistance exercise. Methods: Recreationally trained males (n = 6) and females (n = 7) (mean ± standard deviation, age: 20 ± 1 yrs.; height: 172 ± 8 cm; weight: 73 ± 11 kg; BMI: 24.4 ± 2.2 kg·m−2; training experience: 4 ± 2 yrs.) had limb occlusion pressure determined (50%; right leg: 118 ± 11 mmHg; left leg: 121 ± 13 mmHg) using an automated, self-inflating cuff system during baseline testing. In subsequent sessions, using a randomized, cross-over design, participants completed one of two experimental conditions: (1) Low-load + BFR and (2) High load + non-BFR. In both conditions, participants completed one set of back squats at either 30% (BFR) or 60% (non-BFR) of an estimated 1RM for a max of 30 repetitions, followed by three additional sets with the same loads and a target of 15 repetitions per set. Blood lactate and countermovement jump (CMJ) height were measured pre- and post-back squat. Ratings of perceived exertion (RPE) were assessed following each set. Results: When collapsed across all sets, participants completed significantly more total repetitions in the BFR condition compared to non-BFR (75.0 ± 0.0 vs. 68.23 ± 9.27 reps; p = 0.015; ES: 1.03), but a lower training load volume (2380 ± 728 vs. 4756 ± 1538 kg; p < 0.001; ES: 1.97). There was a significant time-by-condition interaction (p < 0.001), with a greater increase in blood lactate occurring from baseline to post-back squat in the non-BFR condition (11.61 mmol/L, 95%CI: 9.93, 13.28 mmol/L) compared to BFR (5.98 mmol/L, 95%CI: 4.30, 7.65 mmol/L). There was another significant time-by-condition interaction (p = 0.043), with a greater reduction in CMJ occurring in the non-BFR condition (−6.01, 95%CI: −9.14, −2.88 cm; p < 0.001) compared to BFR (−1.50, 95%CI: −1.50, 4.51 cm; p = 0.312). Conclusions: Utilizing a low-load BFR protocol may allow for a higher training volume, yet lower metabolic stress and reduce neuromuscular fatigue compared to lifting at a higher load without the use of BFR.

ABSTRACT Background Surgical resection for pancreas ductal adenocarcinoma (PDAC) remains the mainstay of treatment. Regardless of enhanced survival rates, disparities in patient outcomes and experiences driven by the social determinants of health (SDH) persist. The area deprivation index (ADI) comprises 17 indicators related to education, employment, housing‐quality, and poverty. We sought to examine the impact of ADI on surgical outcomes of PDAC patients. Methods Patients who underwent pancreatoduodenectomy or distal pancreatectomy for PDAC between January 2011 and December 2022 were identified. ADI was calculated using patient zip codes and categorized into quartiles, with the highest indicating the most marginalized. The primary outcome was loss to follow‐up after surgical resection. To account for confounders, a competing risk multivariable regression analysis was used. Results A total of 1001 patients had a mean age of 66.6 (±9.64), with 46.3% ( n = 463) of patients being female. A majority, 94.6% ( n = 947), identified as white, and 64.1% ( n = 641) had at least a college degree. The median length of follow‐up after surgery was 1.8 years (interquartile range: 0.9–3.5). Multivariable analysis adjusting for competing risk of death, showed that patients who are least marginalized are 1.57 times more likely to have their follow‐up than those most marginalized (hazard ratio: 1.57, 95% confidence interval: 1.08–2.29, p = 0.017). Conclusion SDH impact many aspects of patient's care including a higher risk of loss to follow‐up for marginalized patients after surgery for PDAC. Future efforts should seek to identify and lower barriers faced by marginalized patients with system‐level changes to ensure equitable access.

Progression of liver disease is dependent on intercellular signaling, including those mediated by extracellular vesicles (EVs). Within these EVs, microRNAs (miRNAs) are packaged to selectively silence gene expression in recipient cells for upregulating or downregulating a specific pathway. Injured hepatocytes secrete EV-associated miRNAs which can be taken up by liver sinusoidal endothelial cells, immune cells, hepatic stellate cells, and other cell types. In addition, these recipient cells will secrete their own EV-associated miRNAs to propagate a response throughout the tissue and the circulation. In this review, we comment on the implications of EV-miRNAs in the progression of alcohol-associated liver disease, metabolic dysfunction-associated steatohepatitis, viral and parasitic infections, liver fibrosis, and liver malignancies. We summarize how circulating miRNAs can be used as biomarkers and the potential of utilizing EVs and miRNAs as therapeutic methods to treat liver disease.

BACKGROUND AND OBJECTIVES: Stereotactic procedures are used to manage a diverse set of patients across a variety of clinical contexts. The stereotactic devices and software used in these procedures vary between surgeons, but the fundamental principles that constitute safe and accurate execution do not. The aim of this work is to describe these principles to equip readers with a generalizable knowledge base to execute and understand stereotactic procedures. METHODS: A combination of a review of the literature and empirical experience from several experienced surgeons led to the creation of this work. Thus, this work is descriptive and qualitative by nature, and the literature is used to support instead of generate the ideas of this framework. RESULTS: The principles detailed in this work are categorized based on 5 clinical domains: imaging, registration, mechanical accuracy, target planning and adjustment, and trajectory planning and adjustment. Illustrations and tables are used throughout to convey the concepts in an efficient manner. CONCLUSION: Stereotactic procedures are complex, requiring a thorough understanding of each step of the workflow. The concepts described in this work enable functional neurosurgeons with the fundamental knowledge necessary to provide optimal patient care.

BACKGROUND AND OBJECTIVES: Identifying and characterizing sources of targeting error in stereotactic procedures is essential to maximizing accuracy, potentially improving surgical outcomes. We aim to describe a generic framework which characterizes sources of stereotactic inaccuracy. METHODS: We assembled a list of stereotactic systems: ROSA, Neuromate, Mazor Renaissance, ExcelsiusGPS, Cirq, STarFix (FHC), Nexframe, ClearPoint, CRW, and Leksell. We searched the literature for qualitative and quantitative work identifying and quantifying potential sources of inaccuracy and describing each system's implementation using Standards for Reporting Qualitative Research guidelines. Our literature search spanned 1969 to 2024, and various studies were included, with formats ranging from phantom studies to systematic reviews. Keyword searches were conducted, and the details about each system were used to create a framework for identifying and describing the unique targeting error profile of each system. RESULTS: We describe and illustrate the details of various sources of stereotactic inaccuracies and generate a framework to unify these sources into a single framework. This framework entails 5 domains: imaging, registration, mechanical accuracy, target planning and adjustment, and trajectory planning and adjustment. This framework was applied to 10 stereotactic systems. CONCLUSION: This framework provides a rubric to analyze the sources of error for any stereotactic system. Illustrations allow the reader to understand sources of error conceptually so that they may apply them to their practice.