The 5-Item Modified Frailty Index as a Predictor of Postoperative Outcomes in Thoracic Metastatic Epidural Spinal Cord Compression.

BACKGROUND: Patients with thoracic metastatic epidural spinal cord compression (MESCC) often undergo extensive surgical decompression to avoid functional decline. Though limited in scope, scales including the revised cardiac risk index (RCRI) are used to stratify surgical risk to predict perioperative morbidity. This study uses the 5-item modified frailty index (mFI-5) to predict outcomes following transpedicular decompression/fusion for high-grade MESCC. METHODS: A retrospective chart review was conducted on patients who underwent transpedicular decompression and fusion for MESCC (baseline demographics, spinal instability neoplastic score, preoperative and postoperative Bilsky scores, primary cancer type, and RCRI). Primary outcomes included length of stay (LOS), intraoperative estimated blood loss, readmission/reoperation within 90 days of index surgery, 90-day mortality, and posthospitalization disposition. RESULTS: One hundred twenty-seven patients were included in our study. Ninety percent of patients' lesions were Bilsky 2 or greater. Increasing frailty, measured by mFI-5, was a significant predictor of increased LOS (P < 0.01) and 90-day mortality (P < 0.05). Multivariate analysis adjusting for sex, body mass index , and age still showed statistical significance (P < 0.05). MFI-5 was not a significant predictor of readmission/reoperation within 90 days or estimated blood loss. Age - not mFI-5 or RCRI - was a significant predictor for posthospitalization nonhome disposition (P = 0.001). CONCLUSIONS: The mFI-5 can serve as a useful predictor of outcomes after transpedicular decompression and fusion for thoracic MESCC as it can account for the patient's frailty. Our study demonstrated the mFI-5 as a predictor of LOS and 90-day mortality. These results provide a background to both understanding and integrating frailty into decision-making in MESCC.

From Compressed-Sensing to Deep Learning MR: Comparative Biventricular Cardiac Function Analysis in a Patient Cohort.

BACKGROUND: Conventional segmented, retrospectively gated cine (Conv-cine) is challenged in patients with breath-hold difficulties. Compressed sensing (CS) has shown values in cine imaging but generally requires long reconstruction time. Recent artificial intelligence (AI) has demonstrated potential in fast cine imaging. PURPOSE: To compare CS-cine and AI-cine with Conv-cine in quantitative biventricular functions, image quality, and reconstruction time. STUDY TYPE: Prospective human studies. SUBJECTS: 70 patients (age, 39 ± 15 years, 54.3% male). FIELD STRENGTH/SEQUENCE: 3T; balanced steady state free precession gradient echo sequences. ASSESSMENT: Biventricular functional parameters of CS-, AI-, and Conv-cine were measured by two radiologists independently and compared. The scan and reconstruction time were recorded. Subjective scores of image quality were compared by three radiologists. STATISTICAL TESTS: Paired t-test and two related-samples Wilcoxon sign test were used to compare biventricular functional parameters between CS-, AI-, and Conv-cine. Intraclass correlation coefficient (ICC), Bland-Altman analysis, and Kendall's W method were applied to evaluate agreement of biventricular functional parameters and image quality of these three sequences. A P-value <0.05 was considered statistically significant, and standardized mean difference (SMD) < 0. 100 was considered no significant difference. RESULTS: Compared to Conv-cine, no statistically significant differences were identified in CS- and AI-cine function results (all P > 0.05), except for very small differences in left ventricle end-diastole volumes of 2.5 mL (SMD = 0.082) and 4.1 mL (SMD = 0.096), respectively. Bland-Altman scatter plots revealed that biventricular function results were mostly distributed within the 95% confidence interval. All parameters had acceptable to excellent interobserver agreements (ICC: 0.748-0.989). Compared with Conv-cine (84 ± 13 sec), both CS (14 ± 2 sec) and AI (15 ± 2 sec) techniques reduced scan time. Compared with CS-cine (304 ± 17 sec), AI-cine (24 ± 4 sec) reduced reconstruction time. CS-cine demonstrated significantly lower quality scores than Conv-cine, while AI-cine demonstrated similar scores (P = 0.634). CONCLUSION: CS- and AI-cine can achieve whole-heart cardiac cine imaging in a single breath-hold. Both CS- and AI-cine have the potential to supplement the gold standard Conv-cine in studying biventricular functions and benefit patients having difficulties with breath-holds. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Reconnecting the Hand and Arm to the Brain: Efficacy of Neural Interfaces for Sensorimotor Restoration After Tetraplegia.

BACKGROUND AND OBJECTIVES: Paralysis after spinal cord injury involves damage to pathways that connect neurons in the brain to peripheral nerves in the limbs. Re-establishing this communication using neural interfaces has the potential to bridge the gap and restore upper extremity function to people with high tetraplegia. We report a novel approach for restoring upper extremity function using selective peripheral nerve stimulation controlled by intracortical microelectrode recordings from sensorimotor networks, along with restoration of tactile sensation of the hand using intracortical microstimulation. METHODS: A 27-year-old right-handed man with AIS-B (motor-complete, sensory-incomplete) C3-C4 tetraplegia was enrolled into the clinical trial. Six 64-channel intracortical microelectrode arrays were implanted into left hemisphere regions involved in upper extremity function, including primary motor and sensory cortices, inferior frontal gyrus, and anterior intraparietal area. Nine 16-channel extraneural peripheral nerve electrodes were implanted to allow targeted stimulation of right median, ulnar (2), radial, axillary, musculocutaneous, suprascapular, lateral pectoral, and long thoracic nerves, to produce selective muscle contractions on demand. Proof-of-concept studies were performed to demonstrate feasibility of using a brain-machine interface to read from and write to the brain for restoring motor and sensory functions of the participant's own arm and hand. RESULTS: Multiunit neural activity that correlated with intended motor action was successfully recorded from intracortical arrays. Microstimulation of electrodes in somatosensory cortex produced repeatable sensory percepts of individual fingers for restoration of touch sensation. Selective electrical activation of peripheral nerves produced antigravity muscle contractions, resulting in functional movements that the participant was able to command under brain control to perform virtual and actual arm and hand movements. The system was well tolerated with no operative complications. CONCLUSION: The combination of implanted cortical electrodes and nerve cuff electrodes has the potential to create bidirectional restoration of motor and sensory functions of the arm and hand after neurological injury.

Indication as a predictor for outcomes in anterior cervical discectomy and fusion: The impact of myelopathy on disposition.

BACKGROUND: While the indication for Anterior Cervical Discectomy and Fusion (ACDF) may influence the expected postoperative course, there is limited data comparing how length of stay (LOS) and disposition for patients with myelopathy differ from those with radiculopathy. This study aimed to compare LOS and discharge disposition, in patients undergoing ACDF for cervical radiculopathy versus those for myelopathy. METHODS: A retrospective review of all adult ACDF cases between 2013 and 2019 was conducted analyzing sex, age, race, comorbidities, level of surgery, myelopathy measures when applicable, complications, dysphagia, hospital LOS, and discharge disposition. RESULTS: A total of 157 patients were included in the study with 73 patients undergoing an ACDF for radiculopathy and 84 for myelopathy. Univariate analysis determined older age (p < 0.01), male sex (p = 0.03), presence of CKD (p < 0.01) or COPD (p = 0.01), surgery at C3/4 level (p = 0.01), and indication (p < 0.01) as predictors for a discharge to either acute rehabilitation or a skilled nursing facility rather than to home. Multivariate logistic regression demonstrated age and indication as the only independent predictors of disposition, with home disposition being more likely with decreased age (OR 0.92, 95 % CI 0.86-0.98) and radiculopathy as the diagnosis (OR 6.72, 95 % CI 1.22- 37.02). CONCLUSIONS: Myelopathic patients, as compared to those with radiculopathy at presentation, had significantly longer LOS, increased dysphagia, and were more often discharged to a facility. Understanding these two distinct populations as separate entities will streamline the pre and post-surgical care as the current DRG codes and ICD 10 PCS do not differentiate the expected post-operative course in patients undergoing ACDF for myelopathy versus radiculopathy.

Simultaneous second-stage Fowler-Stephens Orchiopexy and microvascular testicular autotransplantation in a patient with prune belly syndrome with cryptorchidism.

We present a case of simultaneous second-stage Fowler-Stephens Orchiopexy (FSO) with microvascular testicular autotransplantation for cryptorchidism and in a patient with prune belly syndrome. At 5 months old, the patient underwent laparoscopic bilateral first-stage FSO with the right testicle located 1 cm from the liver and the left slightly more caudal. An ultrasound on postoperative Day 72 following second-stage FSO and microvascular autotransplantation showed patent testicular vasculature. Our experience shows that this combination technique is safe and effective to supercharge the testicle and augment collateral vessels if clinical suspicion for monotherapy failure is high.

Abnormal L5-S1 Facet Joint Orientation as a Harbinger of Degenerative Spondylolisthesis: A Case Report.

Degenerative spondylolisthesis is a common cause of low back pain and resultant disability in the adult population. The causes of degenerative spondylolisthesis are not entirely understood, though a combination of anatomic and lifestyle factors likely contributes to the development of this pathology. Here, we report a case of a 38-year-old female presenting with low back pain and right lower extremity radiculopathy, found to have degenerative L5-S1 spondylolisthesis, which we postulate developed in part due to the sagittal orientation of her L5-S1 facet joints bilaterally.

Implanted Electrodes for Functional Electrical Stimulation to Restore Upper and Lower Extremity Function: History and Future Directions.

Functional electrical stimulation (FES) to activate nerves and muscles in paralyzed extremities has considerable promise to improve outcome after neurological disease or injury, especially in individuals who have upper motor nerve dysfunction due to central nervous system pathology. Because technology has improved, a wide variety of methods for providing electrical stimulation to create functional movements have been developed, including muscle stimulating electrodes, nerve stimulating electrodes, and hybrid constructs. However, in spite of decades of success in experimental settings with clear functional improvements for individuals with paralysis, the technology has not yet reached widespread clinical translation. In this review, we outline the history of FES techniques and approaches and describe future directions in evolution of the technology.

Reconnecting the Hand and Arm to the Brain: Efficacy of Neural Interfaces for Sensorimotor Restoration after Tetraplegia.

Background: Paralysis after spinal cord injury involves damage to pathways that connect neurons in the brain to peripheral nerves in the limbs. Re-establishing this communication using neural interfaces has the potential to bridge the gap and restore upper extremity function to people with high tetraplegia. Objective: We report a novel approach for restoring upper extremity function using selective peripheral nerve stimulation controlled by intracortical microelectrode recordings from sensorimotor networks, along with restoration of tactile sensation of the hand using intracortical microstimulation. Methods: A right-handed man with motor-complete C3-C4 tetraplegia was enrolled into the clinical trial. Six 64-channel intracortical microelectrode arrays were implanted into left hemisphere regions involved in upper extremity function, including primary motor and sensory cortices, inferior frontal gyrus, and anterior intraparietal area. Nine 16-channel extraneural peripheral nerve electrodes were implanted to allow targeted stimulation of right median, ulnar (2), radial, axillary, musculocutaneous, suprascapular, lateral pectoral, and long thoracic nerves, to produce selective muscle contractions on demand. Proof-of-concept studies were performed to demonstrate feasibility of a bidirectional brain-machine interface to restore function of the participant's own arm and hand. Results: Multi-unit neural activity that correlated with intended motor action was successfully recorded from intracortical arrays. Microstimulation of electrodes in somatosensory cortex produced repeatable sensory percepts of individual fingers for restoration of touch sensation. Selective electrical activation of peripheral nerves produced antigravity muscle contractions. The system was well tolerated with no operative complications. Conclusion: The combination of implanted cortical electrodes and nerve cuff electrodes has the potential to allow restoration of motor and sensory functions of the arm and hand after neurological injury.

A Novel Technique for Lateral Ankle Ligament Reconstruction with Total Ankle Total Talus Replacement: A Case Report.

CASE: A 65-year-old man with severe left talar avascular necrosis, arthritis, and chronic lateral ankle instability underwent total ankle total talus replacement (TATTR) with lateral ligament reconstruction. Tibial component placement was performed using preoperative computed tomography navigation and patient-specific guides. A custom, total talus replacement to mate with the fixed-bearing tibial component was implanted. Last, a modified Brostrom procedure was performed to restore lateral ankle stability. The patient has performed well through 1 year with improved pain-free function. CONCLUSION: This case report details a novel technique for performing a modified Brostrom procedure in conjunction with TATTR to restore lateral ankle stability.

Impact of anemia on acute ischemic stroke outcomes: A systematic review of the literature.

INTRODUCTION: Anemia has been reported in nearly 40% of acute ischemic stroke (AIS) patients and is linked to significant morbidity and disability. The presence of anemia is associated with worse outcomes in AIS, specifically in the presence of large vessel occlusion (LVO). An optimal hemoglobin (Hb) target specific to this pathology has not yet been established. The goal of this review is to systematically review literature that observes the association that exists between AIS outcomes and hemoglobin (Hb) levels. METHODS: A systematic review was performed in accordance with guidelines for the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) to identify studies from 2008-2022. The following inclusion and exclusion criteria were used: studies of adult patients with AIS; must describe outcomes with regard to Hb levels in AIS (not limited to LVO); must be written in English. The clinical variables extracted included Length of Stay (LOS), modified rankin score (mRS), Hb levels, and mortality. RESULTS: A total of 1,154 studies were gathered, with 116 undergoing full text review. 31 studies were included in this review. The age of patients ranged from 61.4 to 77.8. The presence of anemia in AIS increased LOS by 1.7 days on average and these patients also have a 15.2% higher rate of mortality at one year, on average. DISCUSSION: This data suggests that the contemporary thresholds for treating anemia in AIS patients may be inadequate because anemia is strongly associated with poor outcomes (e.g., mRS>2 or mortality) and increased LOS in AIS patients. The current generalized Hb threshold for transfusion (7 g/dL) is also used in AIS patients, however, a more aggressive transfusion parameter should be further explored based on these findings. Further studies are required to confirm these findings and to determine if a more liberal RBCT threshold will result in clinical benefits.

Surface Engineering of Auxetic Scaffolds for Neural and Vascular Differentiation from Human Pluripotent Stem Cells.

Auxetic materials are the materials that can display negative Poisson's ratio that describes the degree to which a material contracts (or expands) transversally when axially strained. Human stem cells sense the mechanical properties of the microenvironment, including material surface properties, stiffness, and Poisson's ratio. In this study, six different auxetic polyurethane (PU) foams with different elastic modulus (0.7-1.8 kPa) and Poisson's ratio (-0.1 to -0.5) are used to investigate lineage specification of human induced pluripotent stem cells (hiPSCs). The surfaces of the foams are modified with chitosan or heparin to enhance the adhesion and proliferation of hiPSCs. Then, the vascular and neural differentiation of hiPSCs are investigated on different foams with distinct elastic modulus and Poisson's ratio. With different auxetic foams, cells show differential adherent density and differentiation capacity. Chitosan and heparin surface functionalization promote the hindbrain and hippocampal markers, but not forebrain markers during neural patterning of hiPSCs. Properly surface engineered auxetic scaffolds can also promote vascular differentiation of hiPSCs. This study represents a versatile and multifunctional scaffold fabrication approach and can lead to a suitable system for establishing hiPSC culture models in applications of neurovascular disease modeling and drug screening.

Bioreactor Expansion Reconfigures Metabolism and Extracellular Vesicle Biogenesis of Human Adipose-derived Stem Cells In Vitro.

Human mesenchymal stem cells (hMSCs), including human adipose tissue-derived stem cells (hASCs), as well as the secreted extracellular vesicles (EVs), are promising therapeutics in treating inflammatory and neural degenerative diseases. However, prolonged expansion can lead to cellular senescence characterized by a gradual loss of self-renewal ability while altering secretome composition and EV generation. Additionally, hMSCs are highly sensitive to biophysical microenvironment in bioreactor systems utilized in scaling production. In this study, hASCs grown on Plastic Plus or Synthemax II microcarriers in a spinner flask bioreactor (SFB) system were compared to traditional 2D culture. The SFB microenvironment was found to increase the expression of genes associated with hASC stemness, nicotinamide adenine dinucleotide (NAD+) metabolism, glycolysis, and the pentose phosphate pathway as well as alter cytokine secretion (e.g., PGE2 and CXCL10). Elevated reactive oxidative species levels in hASCs of SFB culture were observed without increasing rates of cellular senescence. Expression levels of Sirtuins responsible for preventing cellular senescence through anti-oxidant and DNA repair mechanisms were also elevated in SFB cultures. In particular, the EV biogenesis genes were significantly upregulated (3-10 fold) and the EV production increased 40% per cell in SFB cultures of hASCs. This study provides advanced understanding of hASC sensitivity to the bioreactor microenvironment for EV production and bio-manufacturing towards the applications in treating inflammatory and neural degenerative diseases.

Stereotactic radiosurgery and resection for treatment of multiple brain metastases: a systematic review and analysis.

OBJECTIVE: Stereotactic radiosurgery (SRS) has recently emerged as a minimally invasive alternative to resection for treating multiple brain metastases. Given the lack of consensus regarding the application of SRS versus resection for multiple brain metastases, the authors aimed to conduct a systematic literature review of all published work on the topic. METHODS: The PubMed, OVID, Cochrane, Web of Science, and Scopus databases were used to identify studies that examined clinical outcomes after resection or SRS was performed in patients with multiple brain metastases. Radiological studies, case series with fewer than 3 patients, pediatric studies, or national database studies were excluded. Data extracted included patient demographics and mean overall survival (OS). Weighted t-tests and ANOVA were performed. RESULTS: A total of 1300 abstracts were screened, 450 articles underwent full-text review, and 129 studies met inclusion criteria, encompassing 20,177 patients (18,852 treated with SRS and 1325 who underwent resection). The OS for the SRS group was 10.2 ± 6 months, and for the resection group it was 6.5 ± 3.8 months. A weighted ANOVA test comparing OS with covariates of age, sex, and publication year revealed that the treatment group (p = 0.045), age (p = 0.034), and publication year (0.0078) were all independently associated with OS (with SRS, younger age, and later publication year being associated with longer survival), whereas sex (p = 0.95) was not. CONCLUSIONS: For patients with multiple brain metastases, SRS and resection are effective treatments to prolong OS, with published data suggesting that SRS may have a trend toward lengthened survival outcomes. The authors encourage additional work examining outcomes of treatments for multiple brain metastases.

Downstream bioprocessing of human pluripotent stem cell-derived therapeutics.

With the advancement in lineage-specific differentiation from human pluripotent stem cells (hPSCs), downstream cell separation has now become a critical step to produce hPSC-derived products. Since differentiation procedures usually result in a heterogeneous cell population, cell separation needs to be performed either to enrich the desired cell population or remove the undesired cell population. This article summarizes recent advances in separation processes for hPSC-derived cells, including the standard separation technologies, such as magnetic-activated cell sorting, as well as the novel separation strategies, such as those based on adhesion strength and metabolic flux. Specifically, the downstream bioprocessing flow and the identification of surface markers for various cell lineages are discussed. While challenges remain for large-scale downstream bioprocessing of hPSC-derived cells, the rational quality-by-design approach should be implemented to enhance the understanding of the relationship between process and the product and to ensure the safety of the produced cells.

Bioengineering Human Pluripotent Stem Cell-Derived Retinal Organoids and Optic Vesicle-Containing Brain Organoids for Ocular Diseases.

Retinal organoids are three-dimensional (3D) structures derived from human pluripotent stem cells (hPSCs) that mimic the retina's spatial and temporal differentiation, making them useful as in vitro retinal development models. Retinal organoids can be assembled with brain organoids, the 3D self-assembled aggregates derived from hPSCs containing different cell types and cytoarchitectures that resemble the human embryonic brain. Recent studies have shown the development of optic cups in brain organoids. The cellular components of a developing optic vesicle-containing organoids include primitive corneal epithelial and lens-like cells, retinal pigment epithelia, retinal progenitor cells, axon-like projections, and electrically active neuronal networks. The importance of retinal organoids in ocular diseases such as age-related macular degeneration, Stargardt disease, retinitis pigmentosa, and diabetic retinopathy are described in this review. This review highlights current developments in retinal organoid techniques, and their applications in ocular conditions such as disease modeling, gene therapy, drug screening and development. In addition, recent advancements in utilizing extracellular vesicles secreted by retinal organoids for ocular disease treatments are summarized.

Exosomal MicroRNAs as Novel Cell-Free Therapeutics in Tissue Engineering and Regenerative Medicine.

Extracellular vesicles (EVs) are membrane-bound vesicles (50-1000 nm) that can be secreted by all cell types. Microvesicles and exosomes are the major subsets of EVs that exhibit the cell-cell communications and pathological functions of human tissues, and their therapeutic potentials. To further understand and engineer EVs for cell-free therapy, current developments in EV biogenesis and secretion pathways are discussed to illustrate the remaining gaps in EV biology. Specifically, microRNAs (miRs), as a major EV cargo that exert promising therapeutic results, are discussed in the context of biological origins, sorting and packing, and preclinical applications in disease progression and treatments. Moreover, advanced detection and engineering strategies for exosomal miRs are also reviewed. This article provides sufficient information and knowledge for the future design of EVs with specific miRs or protein cargos in tissue repair and regeneration.

Clinical Utility of Routine Postoperative Imaging in Spinal Fusion Surgery: A Systematic Review.

OBJECTIVE: Following spinal fusion surgery, routine imaging is often obtained in all patients regardless of clinical presentation. Such routine imaging may include x-ray, computed tomography, or magnetic resonance imaging studies in both the immediate postoperative period and after discharge. The clinical utility of this practice is questionable. Our goal is to assess the existing literature for evidence of impact on clinical care from routine radiographic surveillance following spinal fusion. METHODS: A systematic search of Embase, Scopus, PubMed, Cochrane, and Ovid databases was performed for studies investigating postoperative imaging following spinal fusion surgery. Studies were analyzed for imaging findings and rates of change in management due to imaging. RESULTS: In total, the review identified 9 studies that separated data by unique patient or by unique clinic visits. The 4 studies reporting per-patient data totaled 475 patients with 328 (69%) receiving routine imaging. Among these, 28 (8.5%) patients had abnormal routine findings with no patients having a change to their clinical course. Of the 5 studies that reported clinic visit data, 3119 patient visits were included with 2365 (76%) clinic visits accompanied by imaging. Across these 5 studies, 146 (6.2%) visits noted abnormal imaging with only 12 (0.5%) subsequent management changes. CONCLUSIONS: Our analysis found that routine imaging after spinal fusion surgery had no direct benefit on clinical management. The utility of baseline imaging for long-term comparison and medicolegal concerns were not studied and remain up to the provider's judgment. Further research is necessary to identify optimal imaging criteria following spinal fusion surgery.

Pudendal tumor mimicking cauda equina syndrome and acute radiculopathy: case report.

INTRODUCTION: Cauda equina syndrome (CES) is most caused by lumbar disc herniation, and the associated treatment involves prompt surgical decompression. Rarer causes of CES include perineural (Tarlov) cysts. CLINICAL PRESENTATION: A 62-year-old female with history of rheumatoid arthritis, hip and knee replacements, and chronic low back pain presented with worsening back pain, left leg weakness and pain for 6 weeks, and bowel/bladder incontinence with diminished sensation in the perianal region for 24 h prior to presentation. MRI demonstrated severe spinal stenosis at L4-S1, central disc herniation at L5-S1, and compression of the cauda equina, consistent with CES. A lumbar decompression was performed. Patient did well at 2-week follow up, but presented 5 weeks post-discharge with increased left leg pain/weakness and genitalia anesthesia. Imaging was unremarkable. Two months later, the patient presented with diminished sensation in the buttocks and bilateral lower extremities and bowel/bladder incontinence. Imaging demonstrated a large cystic presacral mass with involvement of the left sciatic foramen and S3 neural foramen. A team of plastic, orthopedic, and neurological surgeons performed an S3 sacral laminectomy, foraminotomy, partial sacrectomy, and S3 rhizotomy, and excision of the large left hemorrhagic pudendal mass. Final pathology demonstrated a perineural cyst with organizing hemorrhage. On follow-up, the patient's pain and weakness improved. CONCLUSION: CES-like symptoms were initially attributed to a herniated disk. However, lumbar decompression did not resolve symptoms, prompting further radiographic evaluation at two separate presentations. This represents the first reported case of a pudendal tumor causing symptoms initially attributed to a herniated disc.