Hybrid Clot Histomic-Transcriptomic Models Predict Functional Outcome After Mechanical Thrombectomy in Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Histologic and transcriptomic analyses of retrieved stroke clots have identified features associated with patient outcomes. Previous studies have demonstrated the predictive capacity of histology or expression features in isolation. Few studies, however, have investigated how paired histologic image features and expression patterns from the retrieved clots can improve understanding of clot pathobiology and our ability to predict long-term prognosis. We hypothesized that computational models trained using clot histomics and mRNA expression can predict early neurological improvement (ENI) and 90-day functional outcome (modified Rankin Scale Score, mRS) better than models developed using histological composition or expression data alone. METHODS: We performed paired histological and transcriptomic analysis of 32 stroke clots. ENI was defined as a delta-National Institutes of Health Stroke Score/Scale > 4, and a good long-term outcome was defined as mRS ≤2 at 90 days after procedure. Clots were H&E-stained and whole-slide imaged at 40×. An established digital pathology pipeline was used to extract 237 histomic features and to compute clot percent composition (%Comp). When dichotomized by either the ENI or mRS thresholds, differentially expressed genes were identified as those with absolute fold-change >1.5 and q < 0.05. Machine learning with recursive feature elimination (RFE) was used to select clot features and evaluate computational models for outcome prognostication. RESULTS: For ENI, RFE identified 9 optimal histologic and transcriptomic features for the hybrid model, which achieved an accuracy of 90.8% (area under the curve [AUC] = 0.98 ± 0.08) in testing and outperformed models based on histomics (AUC = 0.94 ± 0.09), transcriptomics (AUC = 0.86 ± 0.16), or %Comp (AUC = 0.70 ± 0.15) alone. For mRS, RFE identified 7 optimal histomic and transcriptomic features for the hybrid model. This model achieved an accuracy of 93.7% (AUC = 0.94 ± 0.09) in testing, also outperforming models based on histomics (AUC = 0.90 ± 0.11), transcriptomics (AUC = 0.55 ± 0.27), or %Comp (AUC = 0.58 ± 0.16) alone. CONCLUSION: Hybrid models offer improved outcome prognostication for patients with stroke. Identified digital histology and mRNA signatures warrant further investigation as biomarkers of patient functional outcome after thrombectomy.

Decoding Molecular Mechanisms Underlying Outcomes After Ischemic Stroke Thrombectomy by RNA Sequencing of Retrieved Clots.

BACKGROUND: Transcriptomic profiling has emerged as a powerful tool for exploring the molecular landscape of ischemic stroke clots and providing insights into the pathophysiological mechanisms underlying stroke progression and recovery. In this study, we aimed to investigate the relationship between stroke clot transcriptomes and stroke thrombectomy outcome, as measured by early neurological improvement (ENI) 30 (i.e., a 30% reduction in NIHSS at 24 h post-thrombectomy). HYPOTHESIS: We hypothesized that there exist distinct clot gene expression patterns between good and poor neurological outcomes. METHODS: Transcriptomic analysis of 32 stroke clots retrieved by mechanical thrombectomy was conducted. Transcriptome data of these clots were analyzed to identify differentially expressed genes (DEGs), defined as those with a log(fold-change) ≥ 1.5 and q < 0.05 between samples with good and poor early neurological outcomes. Gene ontology and bioinformatics analyses were performed on genes with p < 0.01 to identify enriched biological processes and Ingenuity Pathway Analysis canonical pathways. Moreover, AUC analysis assessed the predictive power of DEGs for 90-day function outcome (mRS ≤ 2) and cellular composition of clot was predicted using CIBERSORT. We also assessed whether differential enrichment of immune cell types could indicate patient survival. RESULTS: A total of 41 DEGs were identified. Bioinformatics showed that enriched biological processes and pathways emphasized the chronic immune response and matrix metalloproteinase inhibition. Moreover, 25 of the DEGs were found to be significant predictors of 90-day mRS. These genes were indicative of monocytes enrichment and neutrophil depletion in patients with poorer outcomes. CONCLUSION: Our study revealed a distinct gene expression pattern and dysregulated biological pathways associated with ENI. This expression pattern was also predictive of long-term outcome, suggesting a biological link between those ENIs and 90-day mRS.

Evaluating a 3D deep learning pipeline for cerebral vessel and intracranial aneurysm segmentation from computed tomography angiography-digital subtraction angiography image pairs.

OBJECTIVE: Computed tomography angiography (CTA) is the most widely used imaging modality for intracranial aneurysm (IA) management, yet it remains inferior to digital subtraction angiography (DSA) for IA detection, particularly of small IAs in the cavernous carotid region. The authors evaluated a deep learning pipeline for segmentation of vessels and IAs from CTA using coregistered, segmented DSA images as ground truth. METHODS: Using 50 paired CTA-DSA images, the authors trained (n = 27), validated (n = 3), and tested (n = 20) a deep learning model (3D DeepMedic) for cerebrovasculature segmentation from CTA. A landmark-based coregistration algorithm was used for registration and upsampling of CTA images to paired DSA images. Segmented vessels from the DSA were used as the ground truth. Accuracy of the model for vessel segmentation was evaluated using conventional metrics (dice similarity coefficient [DSC]) and vessel segmentation-specific metrics, like connectivity-area-length (CAL). On the test cases (20 IAs), 3 expert raters attempted to detect and segment IAs. For each rater, the authors recorded the rate of IA detection, and for detected IAs, raters segmented and calculated important IA morphology parameters to quantify the differences in IA segmentation by raters to segmentations by DeepMedic. The agreement between raters, DeepMedic, and ground truth was assessed using Krippendorf's alpha. RESULTS: In testing, the DeepMedic model yielded a CAL of 0.971 ± 0.007 and a DSC of 0.868 ± 0.008. The model prediction delineated all IAs and resulted in average error rates of < 10% for all IA morphometrics. Conversely, average IA detection accuracy by the raters was 0.653 (undetected IAs were present to a significantly greater degree on the ICA, likely due to those in the cavernous region, and were significantly smaller). Error rates for IA morphometrics in rater-segmented cases were significantly higher than in DeepMedic-segmented cases, particularly for neck (p = 0.003) and surface area (p = 0.04). For IA morphology, agreement between the raters was acceptable for most metrics, except for the undulation index (α = 0.36) and the nonsphericity index (α = 0.69). Agreement between DeepMedic and ground truth was consistently higher compared with that between expert raters and ground truth. CONCLUSIONS: This CTA segmentation network (DeepMedic trained on DSA-segmented vessels) provides a high-fidelity solution for CTA vessel segmentation, particularly for vessels and IAs in the carotid cavernous region.

Prevalence and risk factors of neck pain in spine surgeons - Are we our own patients?

Aim: This survey of spine surgeons aimed to determine the prevalence of neck pain and identify the associated risk factors. The prevalence of neck pain has been reported in various medical sub-specialities including laparoscopy surgeons, dentists, plastic surgeons, ophthalmologist, urologist and orthopaedic surgeons. However, the literature is lacking on prevalence and risk factors for neck pain in spine surgeons. Methods: A survey questionnaire containing demographic, Neck pain and work practice details was administered to 300 spine surgeons (members of an online group) via text message and e-mail. Results: One hundred and eighty surgeons responded to the survey (response rate, 60%). Three spine surgeons had previous cervical spine surgeries. The 1-month prevalence rate of neck pain was 74.4% (134/180 surgeons). One hundred and eighteen surgeons (88%) reported only neck pain, 16 surgeons (11.9%) had neck pain with radicular arm pain. Only 20.5% of surgeons used a loupe, 18% of surgeons used a microscope, and 24% of surgeons used operating table height at umbilicus during surgery. There was no significant difference between the mean age (p = 0.65), work experience (p = 0.8), time spent in surgery (p = 0.7), and operating table height preference (p = 0.4) when symptomatic and asymptomatic groups were compared. However, a significantly greater percentage of surgeons had a sedentary lifestyle (p = 0.002) & used loupes as compared to microscopes (p = 0.04) in the symptomatic group. There was significant correlation between the surgeon's lifestyle & use of loupe and the incidence of neck pain. Conclusion: Spine surgeons have a higher prevalence of neck pain than general populations and surgeons from other specialties. Considering the high prevalence of neck pain, general health, work, and ergonomic guidelines and recommendations must be formulated to help prevent and decrease the burden of neck pain among spine surgeons.

Does Three-Dimensional Printed Patient-Specific Templates Add Benefit in Revision Surgeries for Complex Pediatric Kyphoscoliosis Deformity with Sublaminar Wires in Situ? A Clinical Study.

STUDY DESIGN: Case-control study. PURPOSE: To evaluate the accuracy of three-dimensional (3D) printed patient-specific templates (PSTs) for placement of pedicle screws (PAs) in patients undergoing revision surgeries for complex kyphoscoliosis deformity with sublaminar wires in situ. OVERVIEW OF LITERATURE: Revision kyphoscoliosis correction surgery in pediatric patients is a challenging task for the treating surgeon. In patients with sublaminar wires in situ, the native anatomical landmarks are obscured, thus making the freehand screw placement technique a highly specialized task. Hence, the concept of using PSTs for insertion of PAs in such surgeries is always intriguing and attractive. METHODS: Five consecutive patients undergoing revision deformity correction with sublaminar wires in situ were included in this study. Patients were divided in two groups based on the technique of PA insertion. A total of 91 PAs were inserted using either a freehand technique (group A) or 3D printed templates (group B) (34 vs. 57). The placement of PAs was classified according to a postoperative computed tomography scan using Neo's classification. Perforation beyond class 2 (>2 mm) was termed as a misplaced screw. The average time required for the insertion of screws was also noted. RESULTS: Mean age, surgical time, and blood loss were recorded. The change in mean Cobb's angle in both groups was also recorded. The difference in rates of misplaced screws was noted in group A and group B (36.21% vs. 2.56%); however, the mean number of misplaced PAs per patient in group A and group B was statistically insignificant (6.5±3.54 vs. 4.67±1.53, p =0.4641). The mean time required to insert a single PA was also statistically insignificant (120±28.28 vs. 90±30 seconds, p =0.3456). CONCLUSIONS: Although 3D printed PSTs help to avoid the misplacement of PAs in revision deformity correction surgeries with sublaminar wires in situ, the mean number of misplaced screws per patient using this technique was found to be statistically insignificant when compared with the freehand technique in this study.

Management of Metastatic Spine and Hip Alveolar Soft Part Sarcoma: Case Report and Review of Literature.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor. Primary or metastatic involvement of the spine is unusual in ASPS. In most case, it is refractory to chemotherapy and radiation. Surgical resection is the most effective intervention. We report the case of a 38-year-old female having ASPS along with metastatic spine and hip involvement treated surgically as a single-stage operation, which is the first of its kind approach to our knowledge. We present the case of a 38-year-old female with simultaneous L4 pathological fracture with symptomatic lumbar canal stenosis without focal neurology and pathological fracture of neck of femur of left hip, secondary to metastatic ASPS. Since both conditions were contributing equally to her disability and demanded early intervention, they were treated simultaneously with intralesional excision of the tumor and posterior stabilization of the spine and left hip proximal femur resection and replaced it with proximal femur endoprosthesis as a single-stage operation. Postoperatively, she had significant relief of radiculopathy and left hip pain. She was mobilized out of bed on the postoperative day 1 and was discharged from hospital on the postoperative day 6. She was given chemotherapy drug sunitib postoperative. At her last follow-up, 20 months' postoperative, she was asymptomatic and was independent in terms of activities of daily living. Metastatic ASPS of the spine and hip is a rare clinical entity. Simultaneous surgical treatment of the spine and hip pathology is technically demanding. If the conditions demands, as in our case, both of them can be managed safely in a single-stage with good midterm outcome.

Management of Proximal Thoracic Kyphoscoliosis with Early Myelopathy in a Young Adult with Neurofibromatosis Type 1: A Case Report and Review of Literature.

INTRODUCTION: Neurofibromatosis (NF) 1 is associated with skeletal deformities. Scoliosis is seen in about 10-64% of NF-1 patients. NF-1 may be associated with dystrophic or non-dystrophic type of curve. There are technical difficulties in treating large dystrophic curve with proximal thoracic kyphoscoliosis in NF-1. This case report and subsequent review of literature attempts to provide a line of management for such difficult lesions. MATERIALS AND METHODS: We present a case of 22-year-old male with NF-1 who came to us with gradually progressive upper back deformity and signs of early myelopathy for 2-3 months. The patient had a 100° proximal thoracic kyphosis and 100° scoliosis with no neurological deficit and brisk reflexes. A single stage posterior fixation with three column osteotomy at the apex of the curve was performed. RESULTS: The kyphosis was corrected to 65° from 100, the scoliosis was corrected to 60° from 100. Clinically, the hump in the upper back was visibly reduced. At 1-year follow-up, the patient remained asymptomatic with no loss of correction and implant breakage on X-ray. CONCLUSION: Large dystrophic proximal thoracic kyphoscoliosis is a difficult lesion to treat and can be managed with an all posterior approach, achieving good cosmetic and neurological outcomes, as demonstrated by this case.

Locally aggressive aneurysmal bone cyst of C4 vertebra treated by total en bloc excision and anterior plus posterior cervical instrumentation.

We are presenting a case of cervical (C4) aneurysmal bone cyst in a 13-year-old girl, came to the outpatient department with neck pain and stiffness since 6 months and normal neurology. We did an en bloc excision of locally aggressive tumor through anterior plus posterior approach and stabilization by lateral mass screw fixation and anterior cervical instrumentation. Involvement of several adjacent cervical vertebrae by an aneurysmal bone cyst is rare, and conventional treatment with curettage and bone grafting is most likely to carry a high rate of recurrence and spinal instability. We recommend complete excision of the tumor and instrumentation in a single stage to avoid instability.

Great Desire for Extended Life and Health amongst the American Public.

People want to live long, healthy lives. Previous surveys suggest very limited interest in much longer lifespans, but we show that stipulating good health changes responses to favor longer lives by an order of magnitude. Advances in aging research hold out hope for greatly slowed aging with associated good health. Understanding the public's desires correctly is important to avoid misallocation of resources for research.

Association between single nucleotide polymorphism in collagen IX and intervertebral disc disease in the Indian population.

BACKGROUND: Symptomatic intervertebral disc degeneration is being recently reported in younger population, questions the basis of its degenerative etiology. Latest evidences show that genetics play a significant role. Collagen IX, an important constituent of disc, is found to be altered in genetically predisposed individuals. Mutations have been reported in COL9A2 and COL9A3 genes, which encode Collagen IX, in Finnish and various other populations. The purpose of the present study is to test the significance of these genes in the Indian population. MATERIALS AND METHODS: One hundred proven cases of intervertebral disc disease (IDD) of various regions of spine were selected for the study, along with matched controls. They were tested for the above mentioned alleles by allelic discrimination method with real-time polymerase chain reaction (PCR) study after isolation of DNA from blood sample. Each blood sample was classified into one of the three types - homozygous, heterozygous, and wild (normal) type allele - separately for COL9A2 and COL9A3 genes. RESULTS: Homozygosity for COL9A2 allelic variation was associated with 100% occurrence of the disease. Heterozygous allele of COL9A2 was significantly higher in the study group (42%) as compared to the control group (17%). In contrast, allelic variation in COL9A3 gene was found to have no significant correlation with disc disease. There was no single patient with homozygous allelic variation for COL9A3, suggesting predominance of COL9A2 variation in the Indian population. CONCLUSION: This candidate gene strategy approach adds considerably to our knowledge of genetic makeup of Indian populations in relation with disc disease. This study highlights importance of COL9A2 gene variation especially of homozygous variety in contrast to COL9A3 variation in causing disc disease in Indian population.

Polyarthritic, symmetric arthropathy in reactive arthritis.

Reactive arthritis (ReA) is an immune mediated disease, clinically associated with oligoarthritis of the lower limbs and sometimes with urethritis and conjunctivitis. In our case, a 24-year-old male presented with severe mutilating arthritis involving both upper and lower extremities in contrast to conventional Reiter's syndrome which presents with asymmetric oligoarthritis. He had multiple well-defined, irregular, erythematous, hyperkeratotic, scaly and itchy plaques, not easily distinguishable from pustular psoriasis. The patient also gave history of circinate balanitis and urethritis. He was started on methotrexate (7.5 mg/week, later escalated to 15 mg/week with 15 mg/day folinic acid supplementation) to which he responded. But when he stopped it on his own, the symptoms recurred. Hence, methotrexate was restarted, but still the patient suffers from fixed flexion deformities in affected joints. Histopathological examination of skin lesions is also suggestive of ReA. Thus, this case report suggests that diagnosis of Reiter's should be considered in symmetrical, mutilating polyarthritis patients with typical skin lesions.