Long-Term Neuropsychiatric, Neurocognitive, and Functional Outcomes of Patients Receiving ECMO: A Systematic Review and Meta-Analysis

BACKGROUND AND OBJECTIVES: Despite the common occurrence of neurologic complications during extracorporeal membrane oxygenation (ECMO) support, data on long-term neuropsychiatric, neurocognitive, and functional outcomes are sparse. We aimed to determine the prevalence of long-term neuropsychiatric symptoms, neurocognitive and functional impairment, and favorable neurologic outcomes in adult patients who receive ECMO. METHODS: PubMed, Embase, Cochrane, Web of Science, and Scopus were searched for text related to ECMO and neuropsychiatric, neurocognitive, and functional outcomes from inception to May 3, 2023. Our primary outcome was the prevalence of neuropsychiatric symptoms (pain/discomfort, anxiety, depression, posttraumatic stress disorder [PTSD], and sleep disturbance) at long-term (≥6 months) follow-up. Our secondary outcomes were the prevalence of neurocognitive impairment (memory, attention, and reasoning), functional impairment (daily activities, physical activity/mobility, and personal/self-care), and favorable neurologic outcomes (Cerebral Performance Category ≤2, modified Rankin scale ≤3, or Glasgow Outcome Scale ≥4). This study was registered in PROSPERO (CRD42023420565). RESULTS: We included 59 studies with 3,280 patients (median age 54 years, 69% male). The cohort consisted of 86% venoarterial (VA)-ECMO (n = 2,819) and 14% venovenous (VV)-ECMO (n = 461) patients. More than 10 tools were used to assess neuropsychiatric and neurocognitive outcomes, indicating a lack of standardization in assessment methodologies. The overall prevalence of neuropsychiatric symptoms was 41% (95% CI 33%-49%): pain/discomfort (52%, 95% CI 42%-63%), sleep disturbance (37%, 95% CI 0%-98%), anxiety (36%, 95% CI 27%-46%), depression (31%, 95% CI 22%-40%), and PTSD (18%, 95% CI 9%-29%). The prevalence of neurocognitive impairment was 38% (95% CI 13%-65%). The prevalence of functional impairment was 52% (95% CI 40%-64%): daily activities (54%, 95% CI 41%-66%), mobility (41%, 95% CI 28%-54%), and self-care (21%, 95% CI 13%-31%). The prevalence of neuropsychiatric symptoms in VV-ECMO patients was higher than that in VA-ECMO patients (55% [95% CI 34%-75%] vs 32% [95% CI 23%-41%], p = 0.01), though the prevalence of neurocognitive and functional impairment was not different between the groups. The prevalence of favorable neurologic outcomes was not different at various follow-ups: 3 months (23%, 95% CI 12%-36%), 6 months (25%, 95% CI 16%-35%), and ≥1 year (28%, 95% CI 21%-36%, p = 0.68). DISCUSSION: A substantial proportion of ECMO patients seemed to experience neuropsychiatric symptoms and neurocognitive and functional impairments at long-term follow-up. Considerable heterogeneity in methodology for gauging these outcomes exists, warranting the need for standardization. Multicenter prospective observational studies are indicated to further investigate risk factors for these outcomes in ECMO-supported patients.

Non-contrast ultrasound image analysis for spatial and temporal distribution of blood flow after spinal cord injury.

Ultrasound technology can provide high-resolution imaging of blood flow following spinal cord injury (SCI). Blood flow imaging may improve critical care management of SCI, yet its duration is limited clinically by the amount of contrast agent injection required for high-resolution, continuous monitoring. In this study, we aim to establish non-contrast ultrasound as a clinically translatable imaging technique for spinal cord blood flow via comparison to contrast-based methods and by measuring the spatial distribution of blood flow after SCI. A rodent model of contusion SCI at the T12 spinal level was carried out using three different impact forces. We compared images of spinal cord blood flow taken using both non-contrast and contrast-enhanced ultrasound. Subsequently, we processed the images as a function of distance from injury, yielding the distribution of blood flow through space after SCI, and found the following. (1) Both non-contrast and contrast-enhanced imaging methods resulted in similar blood flow distributions (Spearman's ρ = 0.55, p < 0.0001). (2) We found an area of decreased flow at the injury epicenter, or umbra (p < 0.0001). Unexpectedly, we found increased flow at the periphery, or penumbra (rostral, p < 0.05; caudal, p < 0.01), following SCI. However, distal flow remained unchanged, in what is presumably unaffected tissue. (3) Finally, tracking blood flow in the injury zones over time revealed interesting dynamic changes. After an initial decrease, blood flow in the penumbra increased during the first 10 min after injury, while blood flow in the umbra and distal tissue remained constant over time. These results demonstrate the viability of non-contrast ultrasound as a clinical monitoring tool. Furthermore, our surprising observations of increased flow in the injury periphery pose interesting new questions about how the spinal cord vasculature reacts to SCI, with potentially increased significance of the penumbra.

Learning Curves for Robot-Assisted Pedicle Screw Placement: Analysis of Operative Time for 234 Cases.

BACKGROUND AND OBJECTIVES: Robot-assisted pedicle screw placement is associated with greater accuracy, reduced radiation, less blood loss, shorter hospital stays, and fewer complications than freehand screw placement. However, it can be associated with longer operative times and an extended training period. We report the initial experience of a surgeon using a robot system at an academic medical center. METHODS: We retrospectively reviewed all patients undergoing robot-assisted pedicle screw placement at a single tertiary care institution by 1 surgeon from 10/2017 to 05/2022. Linear regression, analysis of variance, and cumulative sum analysis were used to evaluate operative time learning curves. Operative time subanalyses for surgery indication, number of levels, and experience level were performed. RESULTS: In total, 234 cases were analyzed. A significant 0.19-minute decrease in operative time per case was observed (r = 0.14, P = .03). After 234 operations, this translates to a reduction in 44.5 minutes from the first to last case. A linear relationship was observed between case number and operative time in patients with spondylolisthesis (-0.63 minutes/case, r = 0.41, P < .001), 2-level involvement (-0.35 minutes/case, r = 0.19, P = .05), and 4-or-more-level involvement (-1.29 minutes/case, r = 0.24, P = .05). This resulted in reductions in operative time ranging from 39 minutes to 1.5 hours. Continued reductions in operative time were observed across the learning, experienced, and expert phases, which had mean operative times of 214, 197, and 146 minutes, respectively ( P < .001). General proficiency in robot-assisted surgery was observed after the 20th case. However, 67 cases were required to reach mastery, defined as the inflection point of the cumulative sum curve. CONCLUSION: This study documents the long-term learning curve of a fellowship-trained spine neurosurgeon. Operative time significantly decreased with more experience. Although gaining comfort with robotic systems may be challenging or require additional training, it can benefit surgeons and patients alike with continued reductions in operative time.

Pearls and pitfalls of ChatGPT in medical oncology.

Recently, ChatGPT has drawn attention to the potential uses of artificial intelligence (AI) in academia. Here, we discuss how ChatGPT can be of value to medicine and medical oncology and the potential pitfalls that may be encountered.

Robot-assisted screw fixation in a cadaver utilizing magnetic resonance imaging-based synthetic computed tomography: toward radiation-free spine surgery. Illustrative case.

BACKGROUND: Synthetic computed tomography (sCT) can be created from magnetic resonance imaging (MRI) utilizing newer software. sCT is yet to be explored as a possible alternative to routine CT (rCT). In this study, rCT scans and MRI-derived sCT scans were obtained on a cadaver. Morphometric analysis was performed comparing the 2 scans. The ExcelsiusGPS robot was used to place lumbosacral screws with both rCT and sCT images. OBSERVATIONS: In total, 14 screws were placed. All screws were grade A on the Gertzbein-Robbins scale. The mean surface distance difference between rCT and sCT on a reconstructed software model was -0.02 ± 0.05 mm, the mean absolute surface distance was 0.24 ± 0.05 mm, and the mean absolute error of radiodensity was 92.88 ± 10.53 HU. The overall mean tip distance for the sCT versus rCT was 1.74 ± 1.1 versus 2.36 ± 1.6 mm (p = 0.24); mean tail distance for the sCT versus rCT was 1.93 ± 0.88 versus 2.81 ± 1.03 mm (p = 0.07); and mean angular deviation for the sCT versus rCT was 3.2° ± 2.05° versus 4.04°± 2.71° (p = 0.53). LESSONS: MRI-based sCT yielded results comparable to those of rCT in both morphometric analysis and robot-assisted lumbosacral screw placement in a cadaver study.

Peptide Macrocyclization Guided by Reversible Covalent Templating.

The creation of complementary products via templating is a hallmark feature of nucleic acid replication. Outside of nucleic acid-like molecules, the templated synthesis of a hetero-complementary copy is still rare. Herein we describe one cycle of templated synthesis that creates homomeric macrocyclic peptides guided by linear instructing strands. This strategy utilizes hydrazone formation to pre-organize peptide oligomeric monomers along the template on a solid support resin, and microwave-assisted peptide synthesis to couple monomers and cyclize the strands. With a flexible templating strand, we can alter the size of the complementary macrocycle products by increasing the length and number of the binding peptide oligomers, showing the potential to precisely tune the size of macrocyclic products. For the smaller macrocyclic peptides, the products can be released via hydrolysis and characterized by ESI-MS.

Disruption of the Blood-Spinal Cord Barrier using Low-Intensity Focused Ultrasound in a Rat Model.

Low-intensity focused ultrasound (LIFU) uses ultrasonic pulsations at lower intensities than ultrasound and is being tested as a reversible and precise neuromodulatory technology. Although LIFU-mediated blood-brain barrier (BBB) opening has been explored in detail, no standardized technique for blood-spinal cord barrier (BSCB) opening has been established to date. Therefore, this protocol presents a method for successful BSCB disruption using LIFU sonication in a rat model, including descriptions of animal preparation, microbubble administration, target selection and localization, as well as BSCB disruption visualization and confirmation. The approach reported here is particularly useful for researchers who need a fast and cost-effective method to test and confirm target localization and precise BSCB disruption in a small animal model with a focused ultrasound transducer, evaluate the BSCB efficacy of sonication parameters, or explore applications for LIFU at the spinal cord, such as drug delivery, immunomodulation, and neuromodulation. Optimizing this protocol for individual use is recommended, especially for advancing future preclinical, clinical, and translational work.

Genomics and Immunomics in the Treatment of Urothelial Carcinoma.

Urothelial carcinoma is a complex cancer with genomic immunomic drivers that have prognostic and predictive treatment implications. Identifying potential targetable alterations via next-generation sequencing and RNA sequencing may allow for elucidation of such targets and exploitation with targeted therapeutics. The role of immunotherapy in treating urothelial carcinoma has shown benefit, but it is unclear in which patients immunotherapeutics have the highest yield. Continuing efforts into better identifying which patients may benefit most from targeted therapies, immunotherapies, and combination therapies may ultimately lead to improved outcomes for patients with this disease.

Tissue-Agnostic Activity of BRAF plus MEK Inhibitor in BRAF V600-Mutant Tumors.

BRAF plus MEK inhibitor combinations are currently FDA-approved for melanoma, non-small cell lung cancer, and anaplastic thyroid cancer. The lack of clinical benefit with BRAF inhibition in BRAF V600-mutated colorectal cancer has prevented its tissue-agnostic drug development. We reviewed the AACR GENIE database for the prevalence of BRAF V600 mutations across tumor types. We reviewed the literature for case reports of clinical responses, outcomes in patients with BRAF V600 mutation-positive nonmelanoma malignancies who received BRAF inhibitor therapy, and data from published adult and pediatric trials. BRAF V600 mutations are prevalent across multiple nonmelanoma malignancies (>40 different tumor types), lead to oncogene addiction, and are clinically actionable in a broad range of adult and pediatric nonmelanoma rare malignancies. Continued tissue-agnostic drug development is warranted beyond the current BRAF plus MEK approved cancers.

Therapeutic Implications of Epidermal Growth Factor Receptor (EGFR) in the Treatment of Metastatic Gastric/GEJ Cancer.

Gastric cancer remains third leading cause of global cancer mortality and is the fifth most common type of cancer in the United States. A select number of gastric cancers harbor alterations in EGFR and/or have amplification/overexpression in the HER2; 2-35 and 9-38%, respectively. The advent of next-generation sequencing of tissue and circulating tumor DNA has allowed for the massive expansion of targeted therapeutics to be employed in many settings. There have been a handful of trials using EGFR inhibitors with modest outcomes. Using novel strategies to target multiple co-mutations as well as identifying immunoregulatory molecule expression patterns will potentially drive future trials and improve gastric cancer patient outcomes.

Cancer Genetics and Therapeutic Opportunities in Urologic Practice.

This article aims to summarize the current literature on genetic alterations related to tumors of the genitourinary tract. Novel associations have recently been reported between specific DNA alterations and genitourinary malignancies. The most common cause of chromosome 3p loss in clear cell renal cell carcinoma is a chromothripsis event, which concurrently generates a chromosome 5q gain. Specific patterns of clear cell renal cell carcinoma metastatic evolution have been uncovered. The first therapy targeting a specific molecular alteration has now been approved for urothelial carcinoma. Germline mutations in DNA damage repair genes and the transcription factor HOXB13 are associated with prostate cancer and may be targeted therapeutically. The genetic associations noted across different genitourinary cancers can inform potential screening approaches and guide novel targeted treatment strategies.

Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?

Immunotherapy (IO) has altered the therapeutic landscape for multiple cancers. There are emerging data from retrospective studies on a subset of patients who do not benefit from IO, instead experiencing rapid progression with dramatic acceleration of disease trajectory, termed 'hyperprogressive disease' (HPD). The incidence of HPD ranges from 4% to 29% from the studies reported. Biological basis and mechanisms of HPD are currently being elucidated, with one theory involving the Fc region of antibodies. Another group has shown EGFR and MDM2/MDM4 amplifications in patients with HPD. This phenomenon has polarized oncologists who debate that this could still reflect the natural history of the disease. Thus, prospective studies are urgently needed to confirm the underlying biology, predict patients who are susceptible to HPD, and determine the modality of therapy post progression.

Bringing wearable devices into oncology practice: fitting smart technology in the clinic.

The new way of acquiring data is at its inception in our ever-changing world. There are now a plethora of opportunities to acquire data; from the data, trends can be calculated, validated, and utilized to solve current problems. Wearable technology has been widely adopted in our society, acquiring roles in many aspects of daily life. With each iteration of a wearable platform, devices are further miniaturized with greater integration of sensors that continually collect and store vast amounts of data. The commercialization of these wearable technologies brings to light opportunities for incorporation of these devices into healthcare, and in particular cancer care. The evolving paradigms of healthcare delivery call for a modification of the current data and results-acquisition structure to better incorporate smart technology implementation. Here we explore the applicability of commercial brand wearable, intelligent technologies in oncology practice and we summarize the workflows and essential concepts that come with wearable smart technology implementation in an oncologic setting.