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1.
Article in English | MEDLINE | ID: mdl-38834445

ABSTRACT

The cervical aortic arch (CAA) is an uncommon congenital anomaly in aortic development, characterized by an elongated aortic arch extending at or above the medial ends of the clavicles. Our objective was to examine the clinical and surgical characteristics of this infrequent condition in the adult population. PubMed, ScienceDirect, SciELO, DOAJ, and Cochrane Library databases were searched until December 2023 for case reports describing the presence of a cervical aortic arch in patients aged ≥18 years. Case reports and series were included if the following criteria were met: (1) description of the cervical aortic arch, (2) age ≥18 years, and (3) English language. The literature search identified 2,325 potentially eligible articles, 61 of whom met our inclusion criteria and included a combined number of 71 patients. Mean age was 38.6 ± 15.4 years, with a female prevalence of 67.1% (47/70). Two-thirds of the CAA were left-sided (48/71, 67.6%), and 62.0% (44/71) of patients presented a concomitant arch aneurysm. Asymptomatic patients were 45.7% (32/70), while of those that were symptomatic, 60.5% (23/38) had symptoms related to vascular-induced compression of trachea and esophagus. Surgery was performed in 42 patients (62.7%) among 67 cases that reported the patient's treatment, and 5 patients (11.9%) among those surgically treated underwent the procedure through an endovascular approach. CAA is an uncommon congenital abnormality that presents challenges in diagnosis and treatment due to its high anatomical variability, diverse clinical manifestations, and presence of concomitant diseases. Surgery seems to be a safe and effective option for the resolution of symptoms.

2.
J Neurosurg Spine ; : 1-9, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38788228

ABSTRACT

OBJECTIVE: Surgery for primary tumors of the mobile spine and sacrum often requires complex reconstruction techniques to cover soft-tissue defects and to treat wound and CSF-related complications. The anatomical, vascular, and immunoregulatory characteristics of the omentum make it an excellent local substrate for the management of radiation soft-tissue injury, infection, and extensive wound defects. This study describes the authors' experience in complex wound reconstruction using pedicled omental flaps to cover defects in surgery for mobile spine and sacral primary tumors. METHODS: A retrospective cohort analysis was conducted on 34 patients who underwent pedicled omental flap reconstruction after en bloc resection of primary sacral and mobile spine tumors between 2010 and 2020. The study focused on assessing the indications for omental flap usage, including soft-tissue coverage, protection against postoperative radiation therapy, infection management, vascular supply for bone grafts, and dural defect and CSF leak repair. Patient demographic characteristics, tumor characteristics, surgical outcomes, and follow-up data were analyzed to determine the procedure's efficacy and complication rates. RESULTS: From 2010 to 2020, 34 patients underwent pedicled omental flap reconstruction after en bloc resection of sacral (24 of 34 [71%]) and mobile spine (10 of 34 [29%]) primary tumors, mostly chordomas. The patient cohort included 21 men and 13 women with a median (range) age of 60 (32-89) years. The most common indication for omental flap was soft-tissue coverage (20 of 34 [59%]). Other indications included protecting abdominopelvic organs for postoperative radiation therapy (6 of 34 [18%]), treating infections (5 of 34 [15%]), providing vascular supply for free fibular bone graft (1 of 34 [3%]), and repairing large dural defects and CSF leak (2 of 34 [6%]). The median (range) follow-up was 24 (0-132) months, during which 71% (24 of 34) of patients did not require additional surgery for wound-related complications. At last follow-up, 59% (20 of 34) had stable disease and 32% (11 of 34) had recurrence, had progression of disease, or had been discharged to hospice after treatment. CONCLUSIONS: The pedicled omentum is an effective local tissue graft that can be used for complex wound reconstruction and management of high-risk closures in primary spine tumors. This technique may have a lower rate of complications than other approaches and may influence surgical planning and flap selection in challenging cases.

3.
Article in English | MEDLINE | ID: mdl-38709827

ABSTRACT

INTRODUCTION: Pelvic metastasis is a common presentation among patients presenting with skeletal metastasis. Image-guided percutaneous cementation of these lesions is becoming increasingly popular for the treatment of these lesions. The objective of this study was to conduct a systematic review that investigates clinical outcomes after percutaneous cementation for pelvic metastasis. METHODS: A systematic review was registered with International Prospective Register of Systematic Reviews and performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, SCOPUS, and Ovid MEDLINE databases. All level I to IV clinical studies published in the English language investigating the clinical outcomes after percutaneous cementation for pelvic metastasis were included. RESULTS: Fourteen studies with 579 patients (278 men, 301 women) and 631 metastatic pelvic lesions were included in the study. The mean follow-up range was 0.7 to 26.4 months. Percutaneous cementation alone was performed in 441 patients (76.2%). Supplemental ablative procedures were performed in 77 patients (13.3%), and supplemental internal fixation using cannulated screws was performed in 107 patients (18.5%). Twelve studies with 430 patients (74.2%) reported pain-related and/or functional outcome scores, of which all studies reported overall clinically notable improvement at short-term follow-up. All studies reported periprocedural complications. Local cement leakage was the most common complication (162/631 lesions, 25.7%) followed by transient local pain (25/579 patients, 4.3%). There were no reported cases of major complications. Seven patients (1.2%) underwent re-intervention for persistent symptoms. CONCLUSIONS: Percutaneous cementation may be an effective method for treating pain and function related to pelvic metastasis. The most common complication was cement leakage surrounding the lesion. The rates of major complications were low, and most complications appeared minor and transient. Additional prospective studies are needed to further assess the efficacy of this procedure. LEVEL OF EVIDENCE: IV, systematic review of level I to IV therapeutic studies.

4.
Spine J ; 24(6): 1056-1064, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38301904

ABSTRACT

BACKGROUND CONTEXT: Giant cell tumor (GCT) of bone is most commonly a benign but locally aggressive primary bone tumor. Spinal GCTs account for 2.7% to 6.5% of all GCTs in bone. En bloc resection, which is the preferred treatment for GCT of the spine, may not always be feasible due to the location, extent of the tumor, and/or the patient's comorbidities. Neoadjuvant denosumab has recently been shown to be effective in downstaging GCT, decreasing the size and extent of GCTs. However, the risk of neurologic deterioration is of major concern for patients with epidural spinal cord compression due to spinal GCT. We experienced this concern when a patient presented to our institution with a midthoracic spinal GCT with progressive epidural disease. The patient was not a good surgical candidate due to severe cardiac disease and uncontrolled diabetes. In considering nonoperative management for this patient, we asked ourselves the following question: What is the risk that this patient will develop neurologic deterioration if we do not urgently operate and opt to treat him with denosumab instead? PURPOSE: The purpose of this study was to assess the literature to (1) determine the risk of neurological deterioration in patients receiving neoadjuvant denosumab for the treatment of spinal GCT and (2) to evaluate the secondary outcomes including radiographic features, surgical/technical complexity, and histological features after treatment. STUDY DESIGN/SETTING: Meta-analysis of the literature. PATIENT SAMPLE: Surgical cases of spinal GCT that (1) presented with type III Campanacci lesions, (2) had epidural disease classified as Bilsky type 1B or above and (3) received neoadjuvant denosumab therapy. OUTCOME MEASURES: The primary outcome measure of interest was neurologic status during denosumab treatment. Secondary outcome measures of interest included radiographic features, surgical/technical complexity, histological features, tumor recurrence, and metastasis. METHODS: Using predetermined inclusion and exclusion criteria, PubMed and Embase electronic databases were searched in August 2022 for articles reporting spinal GCTs treated with neoadjuvant denosumab and surgery. Keywords used were "Spine" AND "Giant Cell Tumor" AND "Denosumab." RESULTS: A total of 428 articles were identified and screened. A total of 22 patients from 12 studies were included for review. 17 patients were female (17/22, 77%), mean age was 32 years (18-62 years) and average follow-up was 21 months. Most GCTs occurred in the thoracic and thoracolumbar spine (11 patients, 50%), followed by 36% in the lumbar spine and 14% in the cervical spine. Almost half of the patients had neurological deficits at presentation (10/22 patients, 45%), and more than 60% had Bilsky 2 or 3 epidural spinal cord compression. None of the patients deteriorated neurologically, irrespective of their neurological status at presentation (p-value=.02, CI -2.58 to -0.18). There were no local recurrences reported. One patient was found to have lung nodules postoperatively. More than 90% of cases had decreased overall tumor size and increased bone formation. Surgical dissection was facilitated in more than 85% of those who had documented surgical procedures. Four patients (18%) underwent initial spinal stabilization followed by neoadjuvant denosumab and then surgical excision of the GCT. Regarding the histologic analyses, denosumab eradicated the giant cells in 95% of cases. However, residual Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL)-positive stromal cells were noted, in 27% (6 cases). CONCLUSIONS: Neoadjuvant denosumab was a safe and effective means of treating spinal GCTs prior to surgery. Neurologic status remained stable or improved in all cases included in our review, irrespective of the presenting neurologic status. The most appropriate dosage and duration of denosumab therapy is yet to be determined. We recommend future well-designed studies to further evaluate the use of neoadjuvant denosumab for patients with spinal GCT.


Subject(s)
Denosumab , Giant Cell Tumor of Bone , Neoadjuvant Therapy , Spinal Neoplasms , Denosumab/therapeutic use , Humans , Spinal Neoplasms/drug therapy , Spinal Neoplasms/surgery , Giant Cell Tumor of Bone/drug therapy , Giant Cell Tumor of Bone/pathology , Giant Cell Tumor of Bone/surgery , Bone Density Conservation Agents/therapeutic use , Spinal Cord Compression/etiology , Spinal Cord Compression/surgery , Spinal Cord Compression/drug therapy , Adult , Male , Female , Thoracic Vertebrae/surgery , Thoracic Vertebrae/pathology , Middle Aged
5.
Cancers (Basel) ; 16(2)2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38275879

ABSTRACT

BACKGROUND: Spinal metastases are a significant cause of morbidity in patients with advanced cancer, and management often requires surgical intervention. Although prior studies have identified factors that influence outcomes with surgery, the ability of these factors to predict outcomes remains unclear in the era of contemporary therapies, and there is a need to better identify patients who are likely to benefit from surgery. METHODS: We performed a single-center, retrospective analysis to evaluate risk factors for poor outcomes in patients with spinal metastases treated with surgery. The primary outcome was mortality at 180 days. RESULTS: A total of 128 patients were identified. Age ≥ 65 years at surgery (p = 0.0316), presence of extraspinal metastases (p = 0.0110), and ECOG performance scores >1 (p = 0.0397) were associated with mortality at 180 days on multivariate analysis. These factors and BMI ≤ 30 mg/kg2 (p = 0.0008) were also associated with worse overall survival. CONCLUSIONS: Age > 65, extraspinal metastases, and performance status scores >1 are factors associated with mortality at 180 days in patients with spinal metastases treated with surgery. Patients with these factors and BMI ≤ 30 mg/kg2 had worse overall survival. Our results support multidisciplinary discussions regarding the benefits and risks associated with surgery in patients with these risk factors.

6.
Disabil Rehabil ; 46(4): 697-704, 2024 Feb.
Article in English | MEDLINE | ID: mdl-36755434

ABSTRACT

PURPOSE: Exercise fidelity is a fundamental aspect of exercise prescription by physiotherapists. Assessing exercise fidelity via telehealth (videoconference) is potentially useful but its reproducibility has not been assessed. The objective was to evaluate agreement (reproducibility) of video rating of calf exercise fidelity within (over four weeks) and between telehealth raters and compared with live rating. METHODS: Nineteen videos of participants with AT undertaking calf exercises were rated by physiotherapists in person (live) and by watching pre-recorded videos (replicating telehealth). Three forms of agreement were assessed: (i) between live assessment and recorded video (telehealth) assessment; (ii) between telehealth raters (inter-rater); (iii) agreement within telehealth raters over four weeks (intra-rater). RESULTS: There was weak to almost perfect agreement (Kappa = 0.65 to 1.00, rater 1, Kappa = 0.57 to 1.00, rater 2) between the telehealth and live raters. There was moderate to almost perfect agreement (Kappa = 0.65 to 1.00) when assessing intra-rater reliability, aside from one of the six criteria (quality of movement). CONCLUSION: Assessing calf exercise fidelity via videos recorded on Zoom® appears to demonstrate weak or greater agreement versus live rating and over time. Inter-rater agreement was lower, suggesting that the criteria developed may be better suited to use by individual raters over time.Implications for rehabilitationTelehealth assessment (when compared with live, in person assessment) shows a moderate or greater agreement for the majority of assessment criteria when assessing calf exercise fidelity.The calf exercise fidelity criteria developed can be used as an adjunct to assessment and management of people with Achilles Tendinopathy.Intra-rater assessment was shown to be moderately or more consistent over a four-week period when assessing calf exercise fidelity.


Subject(s)
Achilles Tendon , Musculoskeletal Diseases , Tendinopathy , Humans , Reproducibility of Results , Exercise Therapy , Observer Variation
7.
J Am Acad Orthop Surg ; 32(1): 41-46, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37580051

ABSTRACT

BACKGROUND: Although the medial clear space (MCS) is commonly used to assess talar alignment and ankle stability, its measurement is variable with multiple reported normal values. We have observed that the lateral tibial shaft is a reliable landmark to assess talar alignment. The objective of the current investigation was to determine the normal relationship of the lateral tibia to the superolateral talus using a tangent drawn inferiorly from the lateral tibial shaft, which we refer to as the "lateral tibial line" (LTL). METHODS: The relationship of the LTL to the superolateral talus was assessed by three reviewers on 99 standing ankle mortise radiographs in uninjured patients. This relationship was quantified by measuring the distance (in millimeters) between the LTL and the superolateral talus. In addition, the interobserver reliability of the LTL measurement was recorded and compared with that of the MCS. RESULTS: The median value for the distance between the superolateral talus and LTL was -0.50 mm with an interquartile range of -1.4 to 0.0 mm. The LTL was within 1 mm of the lateral talus in 176 of 297 reviewer measurements (59.3%). Moreover, it was either lateral to or at most 1 mm medial to the lateral talus in 90.9% of cases. The LTL measurement also demonstrated good interobserver reliability (0.764, 95% confidence interval, 0.670 to 0.834), similar to the measurement of MCS (0.742, 95% confidence interval, 0.539 to 0.846). CONCLUSIONS: The relationship between the LTL and superolateral talus is easily measured with good reliability for assessing the anatomic relationship of the tibia and talus. The LTL uncommonly fell more than 1 mm medial to the superolateral talus, as might be seen with displaced ankle fractures. These findings will hopefully serve as a basis for future studies evaluating its role in assessing lateral displacement and stability of isolated fibula fractures. LEVEL OF EVIDENCE: Level III, retrospective review.


Subject(s)
Fractures, Bone , Talus , Humans , Ankle/diagnostic imaging , Tibia/diagnostic imaging , Reproducibility of Results , Ankle Joint/diagnostic imaging , Talus/diagnostic imaging
8.
IEEE Trans Med Imaging ; 43(1): 351-365, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37590109

ABSTRACT

3D imaging enables accurate diagnosis by providing spatial information about organ anatomy. However, using 3D images to train AI models is computationally challenging because they consist of 10x or 100x more pixels than their 2D counterparts. To be trained with high-resolution 3D images, convolutional neural networks resort to downsampling them or projecting them to 2D. We propose an effective alternative, a neural network that enables efficient classification of full-resolution 3D medical images. Compared to off-the-shelf convolutional neural networks, our network, 3D Globally-Aware Multiple Instance Classifier (3D-GMIC), uses 77.98%-90.05% less GPU memory and 91.23%-96.02% less computation. While it is trained only with image-level labels, without segmentation labels, it explains its predictions by providing pixel-level saliency maps. On a dataset collected at NYU Langone Health, including 85,526 patients with full-field 2D mammography (FFDM), synthetic 2D mammography, and 3D mammography, 3D-GMIC achieves an AUC of 0.831 (95% CI: 0.769-0.887) in classifying breasts with malignant findings using 3D mammography. This is comparable to the performance of GMIC on FFDM (0.816, 95% CI: 0.737-0.878) and synthetic 2D (0.826, 95% CI: 0.754-0.884), which demonstrates that 3D-GMIC successfully classified large 3D images despite focusing computation on a smaller percentage of its input compared to GMIC. Therefore, 3D-GMIC identifies and utilizes extremely small regions of interest from 3D images consisting of hundreds of millions of pixels, dramatically reducing associated computational challenges. 3D-GMIC generalizes well to BCS-DBT, an external dataset from Duke University Hospital, achieving an AUC of 0.848 (95% CI: 0.798-0.896).


Subject(s)
Breast , Imaging, Three-Dimensional , Humans , Imaging, Three-Dimensional/methods , Breast/diagnostic imaging , Mammography/methods , Neural Networks, Computer , Image Processing, Computer-Assisted/methods
9.
J Orthop Case Rep ; 13(9): 137-143, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37753123

ABSTRACT

Introduction: Hypervascular tumors such as renal and thyroid carcinoma have a significant risk of intraoperative bleeding. To help mitigate bleeding, interventional preoperative embolization is traditionally used; however, it is success is highly variable. This is the first case report to discuss using expandable balloon implants with a minimally invasive approach to achieve fracture fixation and tamponade acute intraoperative bleeding. Case Report: A 48-year-old male with clear-cell renal cell carcinoma presented with a left humeral shaft pathologic fracture. The patient was scheduled to undergo open biopsy, curettage of tumor, and fracture fixation with an intramedullary device. Intraoperatively, during open biopsy and curettage, brisk bleeding was encountered, which ceased after inserting an intramedullary photodynamic bone stabilization implant (IlluminOss). The implant's balloon expanded to the diameter of the humerus allowing for tamponade, fracture stability, and a minimally invasive approach. Conclusion: We present a possible intraoperative option for achieving control of bleeding in pathologic long bone fractures by deploying a photodynamic stabilization device. The method described can have applications in specific patients and obviate the need for pre-operative embolization for highly vascular tumors due to the implant's ability to create tamponade within the bone.

10.
Clin Cancer Res ; 29(23): 4844-4852, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37747813

ABSTRACT

PURPOSE: Chondrosarcomas are the most common primary bone tumor in adults. Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are prevalent. We aimed to assess the clinico-genomic properties of IDH mutant versus IDH wild-type (WT) chondrosarcomas as well as alterations in other genes. EXPERIMENTAL DESIGN: We included 93 patients with conventional and dedifferentiated chondrosarcoma for which there were available clinical next-generation sequencing data. Clinical and genomic data were extracted and compared between IDH mutant and IDH WT chondrosarcomas and between TP53 mutant and TP53 WT chondrosarcomas. RESULTS: IDH1 and IDH2 mutations are prevalent in chondrosarcoma (50.5%), more common in chondrosarcomas arising in the extremities, associated with higher age at diagnosis, and more common in dedifferentiated chondrosarcomas compared with grades 1-3 conventional chondrosarcoma. There was no difference in survival based on IDH mutation in univariate and multivariate analyses. TP53 mutation was the next most prevalent (41.9%) and is associated with worse overall survival and metastasis-free survival in both univariate and multivariate analyses. TP53 mutation was also associated with higher risk of recurrence following curative-intent surgery and worse survival among patients that presented with de novo metastatic disease. CONCLUSIONS: IDH mutations are prevalent in chondrosarcoma though were not associated with survival outcomes in this cohort. TP53 mutations were the next most common alteration and were associated with worse outcomes.


Subject(s)
Bone Neoplasms , Chondrosarcoma , Adult , Humans , Mutation , Chondrosarcoma/genetics , Chondrosarcoma/pathology , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Bone and Bones/pathology , Genomics , Isocitrate Dehydrogenase/genetics , Isocitrate Dehydrogenase/metabolism , Tumor Suppressor Protein p53/genetics
11.
Heart Views ; 24(3): 160-162, 2023.
Article in English | MEDLINE | ID: mdl-37584023

ABSTRACT

A 67-year-old man with inferior wall ST-segment elevation myocardial infarction underwent Impella-assisted percutaneous coronary intervention complicated by unilateral left-sided pulmonary edema and cardiogenic shock due to severe mitral valve regurgitation. Surgery was deferred due to hemodynamic instability and a high risk of mortality, so he underwent a MitraClip procedure. Mitral regurgitation (MR) is a catastrophic mechanical complication of myocardial infarction that leads to the development of pulmonary edema, cardiogenic shock, and death. After the procedure, the patient significantly reduces MR with a resolution of pulmonary edema. Acute MR can rarely present as a unilateral left-sided pulmonary edema delaying diagnosis and treatment. Transcatheter edge-to-edge repair can be a safe alternative for patients who are at high risk for surgery.

12.
J Neurosurg Spine ; 39(5): 611-617, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37060308

ABSTRACT

OBJECTIVE: The purpose of this study was to analyze risk factors for sacral fracture following noninstrumented partial sacral amputation for en bloc chordoma resection. METHODS: A multicenter retrospective chart review identified patients who underwent noninstrumented partial sacral amputation for en bloc chordoma resection with pre- and postoperative imaging. Hounsfield units (HU) were measured in the S1 level. Sacral amputation level nomenclature was based on the highest sacral level with bone removed (e.g., S1 foramen amputation at the S1-2 vestigial disc is an S2 sacral amputation). Variables collected included basic demographics, patient comorbidities, surgical approach, preoperative radiographic details, neoadjuvant and adjuvant radiation therapy, and postoperative sacral fracture data. RESULTS: A total of 101 patients (60 men, 41 women) were included; they had an average age of 69 years, BMI of 29 kg/m2, and follow-up of 60 months. The sacral amputation level was S1 (2%), S2 (37%), S3 (44%), S4 (9%), and S5 (9%). Patients had a posterior-only approach (77%) or a combined anterior-posterior approach (23%), with 10 patients (10%) having partial sacroiliac (SI) joint resection. Twenty-seven patients (27%) suffered a postoperative sacral fracture, all occurring between 1 and 7 months after the index surgery. Multivariable logistic regression analysis demonstrated S1 or S2 sacral amputation level (p = 0.001), combined anterior-posterior approach (p = 0.0064), and low superior S1 HU (p = 0.027) to be independent predictors of sacral fracture. The fracture rate for patients with superior S1 HU < 225, 225-300, and > 300 was 38%, 15%, and 9%, respectively. An optimal superior S1 HU cutoff of 300 was found to maximize sensitivity (89%) and specificity (42%) in predicting postamputation sacral fracture. In addition, the fracture rate for patients who underwent partial SI joint resection was 100%. CONCLUSIONS: Patients with S1 or S2 partial sacral amputations, a combined anterior-posterior surgical approach, low superior S1 HU, and partial SI joint resection are at higher risk for postoperative sacral fracture following en bloc chordoma resection and should be considered for spinopelvic instrumentation at the index procedure.


Subject(s)
Chordoma , Fractures, Bone , Neck Injuries , Spinal Fractures , Spinal Neoplasms , Male , Humans , Female , Aged , Chordoma/diagnostic imaging , Chordoma/surgery , Retrospective Studies , Neurosurgical Procedures/adverse effects , Risk Factors , Spinal Fractures/diagnostic imaging , Spinal Fractures/surgery , Spinal Fractures/etiology , Fractures, Bone/surgery , Neck Injuries/surgery , Sacrum/diagnostic imaging , Sacrum/surgery , Spinal Neoplasms/diagnostic imaging , Spinal Neoplasms/surgery , Treatment Outcome
13.
Sci Adv ; 9(2): eadd8417, 2023 01 13.
Article in English | MEDLINE | ID: mdl-36630507

ABSTRACT

Amphetamine (AMPH) is a psychostimulant that is commonly abused. The stimulant properties of AMPH are associated with its ability to increase dopamine (DA) neurotransmission. This increase is promoted by nonvesicular DA release mediated by reversal of DA transporter (DAT) function. Syntaxin 1 (Stx1) is a SNARE protein that is phosphorylated at Ser14 by casein kinase II. We show that Stx1 phosphorylation is critical for AMPH-induced nonvesicular DA release and, in Drosophila melanogaster, regulates the expression of AMPH-induced preference and sexual motivation. Our molecular dynamics simulations of the DAT/Stx1 complex demonstrate that phosphorylation of these proteins is pivotal for DAT to dwell in a DA releasing state. This state is characterized by the breakdown of two key salt bridges within the DAT intracellular gate, causing the opening and hydration of the DAT intracellular vestibule, allowing DA to bind from the cytosol, a mechanism that we hypothesize underlies nonvesicular DA release.


Subject(s)
Dopamine , Syntaxin 1 , Animals , Amphetamine/pharmacology , Dopamine/metabolism , Dopamine Plasma Membrane Transport Proteins/metabolism , Drosophila melanogaster/metabolism , Phosphorylation , Syntaxin 1/genetics , Syntaxin 1/metabolism
14.
Spine (Phila Pa 1976) ; 48(4): 261-269, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36255369

ABSTRACT

STUDY DESIGN: A retrospective database study. OBJECTIVE: The purpose of our study was to compare the perioperative complications and reoperation rates after anterior cervical discectomy and fusion (ACDF), cervical disk arthroplasty (CDA), and posterior cervical foraminotomy (PCF) in patients treated for cervical radiculopathy. SUMMARY OF BACKGROUND DATA: Cervical radiculopathy results from compression or irritation of nerve roots in the cervical spine. While most cervical radiculopathy is treated nonoperatively, ACDF, CDA, and PCF are the techniques most commonly used if operative intervention is indicated. There is limited research evaluating the perioperative complications of these surgical techniques. MATERIALS AND METHODS: A retrospective review was performed using the PearlDiver Patient Record Database to identify cases of cervical radiculopathy that underwent ACDF, CDA, or PCF at one or two levels from 2007 to 2016. Perioperative complications and reoperations following each of the procedures were assessed. RESULTS: During the study period, 25,051 patients underwent ACDF, 522 underwent CDA, and 3986 underwent PCF. After propensity score matching, each of the three groups consisted of 507 patients. Surgical site infection rates were highest after PCF (2.17%) compared with ACDF (0.20%) and CDA (0.59%) at 30 days and three months ( P =0.003, P <0.001), respectively. New-onset cervicalgia was highest following ACDF (34.32%) and lowest after PCF (22.88%) at three and six months ( P <0.001 and P =0.003), respectively. Revision surgeries were highest among those who underwent CDA (6.90%) versus ACDF (3.16%) and PCF (3.55%) at six months ( P =0.007). Limb paralysis was significantly higher after PCF compared with CDA and ACDF at six months ( P <0.017). CONCLUSIONS: The rate of surgical site infection was higher in PCF compared with ACDF and CDA. New-onset cervicalgia was higher after ACDF compared with PCF and CDA at short-term follow-up. Revision surgeries were highest among those undergoing CDA and lowest in those undergoing ACDF. LEVEL OF EVIDENCE: 3.


Subject(s)
Radiculopathy , Spinal Fusion , Humans , Reoperation/adverse effects , Radiculopathy/surgery , Neck Pain/surgery , Retrospective Studies , Surgical Wound Infection/surgery , Treatment Outcome , Cervical Vertebrae/surgery , Diskectomy/adverse effects , Spinal Fusion/methods
15.
Sci Transl Med ; 14(664): eabo4802, 2022 Sep 28.
Article in English | MEDLINE | ID: mdl-36170446

ABSTRACT

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has a high sensitivity in detecting breast cancer but often leads to unnecessary biopsies and patient workup. We used a deep learning (DL) system to improve the overall accuracy of breast cancer diagnosis and personalize management of patients undergoing DCE-MRI. On the internal test set (n = 3936 exams), our system achieved an area under the receiver operating characteristic curve (AUROC) of 0.92 (95% CI: 0.92 to 0.93). In a retrospective reader study, there was no statistically significant difference (P = 0.19) between five board-certified breast radiologists and the DL system (mean ΔAUROC, +0.04 in favor of the DL system). Radiologists' performance improved when their predictions were averaged with DL's predictions [mean ΔAUPRC (area under the precision-recall curve), +0.07]. We demonstrated the generalizability of the DL system using multiple datasets from Poland and the United States. An additional reader study on a Polish dataset showed that the DL system was as robust to distribution shift as radiologists. In subgroup analysis, we observed consistent results across different cancer subtypes and patient demographics. Using decision curve analysis, we showed that the DL system can reduce unnecessary biopsies in the range of clinically relevant risk thresholds. This would lead to avoiding biopsies yielding benign results in up to 20% of all patients with BI-RADS category 4 lesions. Last, we performed an error analysis, investigating situations where DL predictions were mostly incorrect. This exploratory work creates a foundation for deployment and prospective analysis of DL-based models for breast MRI.


Subject(s)
Breast Neoplasms , Deep Learning , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Female , Humans , Magnetic Resonance Imaging/methods , ROC Curve , Retrospective Studies
16.
J Clin Med ; 11(17)2022 Aug 24.
Article in English | MEDLINE | ID: mdl-36078889

ABSTRACT

Carbon fiber offers numerous material benefits including reduced wear, high strength-to-weight ratio, a similar elastic modulus to that of bone, and high biocompatibility. Carbon fiber implants are increasingly used in multiple arenas within orthopaedic surgery, including spine, trauma, arthroplasty, and oncology. In the orthopaedic oncologic population, the radiolucency of carbon fiber facilitates post-operative imaging for tumor surveillance or recurrence, the monitoring of bony healing and union, and radiation mapping and delivery.

17.
Semin Roentgenol ; 57(2): 145-148, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35523528

ABSTRACT

Abbreviated breast MRI is an emerging technique that is being incorporated into clinical practice for breast cancer imaging and screening. Conventional breast MRI includes barriers such as high examination cost and lengthy examination times which make its use in the screening setting challenging. Abbreviated MRI aims to address these pitfalls by reducing overall examination time and increasing accessibility to MRI while preserving diagnostic accuracy. Sequences selected for abbreviated MRI protocols allow for preserved accuracy in breast cancer detection and characterization. Novel techniques such as ultrafast imaging are being used to provide kinetic information from early post-contrast imaging.


Subject(s)
Breast Neoplasms , Breast , Breast/diagnostic imaging , Breast Neoplasms/diagnostic imaging , Contrast Media , Female , Humans , Magnetic Resonance Imaging/methods , Mass Screening/methods , Sensitivity and Specificity
18.
J Comput Biol ; 29(5): 409-424, 2022 05.
Article in English | MEDLINE | ID: mdl-35325548

ABSTRACT

Long-range regulatory interactions among genomic regions are critical for controlling gene expression, and their disruption has been associated with a host of diseases. However, when modeling the effects of regulatory factors, most deep learning models either neglect long-range interactions or fail to capture the inherent 3D structure of the underlying genomic organization. To address these limitations, we present a Graph Convolutional Model for Epigenetic Regulation of Gene Expression (GC-MERGE). Using a graph-based framework, the model incorporates important information about long-range interactions via a natural encoding of genomic spatial interactions into the graph representation. It integrates measurements of both the global genomic organization and the local regulatory factors, specifically histone modifications, to not only predict the expression of a given gene of interest but also quantify the importance of its regulatory factors. We apply GC-MERGE to data sets for three cell lines-GM12878 (lymphoblastoid), K562 (myelogenous leukemia), and HUVEC (human umbilical vein endothelial)-and demonstrate its state-of-the-art predictive performance. Crucially, we show that our model is interpretable in terms of the observed biological regulatory factors, highlighting both the histone modifications and the interacting genomic regions contributing to a gene's predicted expression. We provide model explanations for multiple exemplar genes and validate them with evidence from the literature. Our model presents a novel setup for predicting gene expression by integrating multimodal data sets in a graph convolutional framework. More importantly, it enables interpretation of the biological mechanisms driving the model's predictions.


Subject(s)
Epigenesis, Genetic , Neural Networks, Computer , Gene Expression , Genome , Genomics , Humans
19.
J Clin Neurosci ; 94: 266-270, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34863449

ABSTRACT

BACKGROUND: Early instrumentation failure (EIF) after pedicle subtraction osteotomy (PSO) is a known complication of adult spine deformity (ASD) correction. In contrast to the more common failure that occurs secondary to pseudarthrosis, early instrumentation failure (<6 months after surgery) and its risk factors are not as well understood. OBJECTIVE: To identify risk factors for EIF in patients undergoing PSO for ASD correction. METHODS: Patients with ASD who underwent correction with PSO from 2013 to 2018 were retrospectively reviewed. Demographic characteristics, number of rods, spinopelvic parameters, bone density derived from computed tomography (CT) attenuation in Hounsfield units (HU), Global Alignment and Proportion (GAP) score, and type of instrumentation failure were evaluated. Potential risk factors for EIF were analyzed. RESULTS: 9 out of 46 (19.5%) patients who underwent PSO had EIF. All 9 patients with EIF had 2-rod constructs and failed secondary to rod fracture. The number of rods used in the EIF group was significantly lower than the non-EIF group (2.00 ± 0.00 vs 2.81 ± 0.995, p = .000. The EIF group demonstrated a significantly higher pre-op PI (77.33 ± 13.23), p = .022, pre-op PT (37.22 ± 6.46),p = .012, and post-op SVA (89.96 ± 23.85), p = .028 compared to the non-EIF group. CONCLUSION: High pre-op PI, pre-op PT, and post-op SVA were significant risk factors associated with EIF after PSO. Use of multiple rod constructs are protective and may help mitigate risk of EIF in these patients.


Subject(s)
Spinal Fusion , Adult , Humans , Lumbar Vertebrae , Osteotomy , Retrospective Studies , Risk Factors , Spinal Fusion/adverse effects
20.
Neurosurg Focus ; 50(5): E5, 2021 05.
Article in English | MEDLINE | ID: mdl-33932935

ABSTRACT

OBJECTIVE: Frailty is recognized as an important consideration in patients with cancer who are undergoing therapies, including spine surgery. The definition of frailty in the context of spinal metastases is unclear, and few have studied such markers and their association with postoperative outcomes and survival. Using national databases, the metastatic spinal tumor frailty index (MSTFI) was developed as a tool to predict outcomes in this specific patient population and has not been tested with external data. The purpose of this study was to test the performance of the MSTFI with institutional data and determine whether machine learning methods could better identify measures of frailty as predictors of outcomes. METHODS: Electronic health record data from 479 adult patients admitted to the Massachusetts General Hospital for metastatic spinal tumor surgery from 2010 to 2019 formed a validation cohort for the MSTFI to predict major complications, in-hospital mortality, and length of stay (LOS). The 9 parameters of the MSTFI were modeled in 3 machine learning algorithms (lasso regularization logistic regression, random forest, and gradient-boosted decision tree) to assess clinical outcome prediction and determine variable importance. Prediction performance of the models was measured by computing areas under the receiver operating characteristic curve (AUROCs), calibration, and confusion matrix metrics (positive predictive value, sensitivity, and specificity) and was subjected to internal bootstrap validation. RESULTS: Of 479 patients (median age 64 years [IQR 55-71 years]; 58.7% male), 28.4% had complications after spine surgery. The in-hospital mortality rate was 1.9%, and the mean LOS was 7.8 days. The MSTFI demonstrated poor discrimination for predicting complications (AUROC 0.56, 95% CI 0.50-0.62) and in-hospital mortality (AUROC 0.69, 95% CI 0.54-0.85) in the validation cohort. For postoperative complications, machine learning approaches showed a greater advantage over the logistic regression model used to develop the MSTFI (AUROC 0.62, 95% CI 0.56-0.68 for random forest vs AUROC 0.56, 95% CI 0.50-0.62 for logistic regression). The random forest model had the highest positive predictive value (0.53, 95% CI 0.43-0.64) and the highest negative predictive value (0.77, 95% CI 0.72-0.81), with chronic lung disease, coagulopathy, anemia, and malnutrition identified as the most important predictors of postoperative complications. CONCLUSIONS: This study highlights the challenges of defining and quantifying frailty in the metastatic spine tumor population. Further study is required to improve the determination of surgical frailty in this specific cohort.


Subject(s)
Frailty , Spinal Neoplasms , Adult , Female , Frailty/diagnosis , Humans , Machine Learning , Male , Middle Aged , Neurosurgical Procedures , Postoperative Complications/etiology , Spinal Neoplasms/surgery
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