Publications by authors named "James Kang"

389 Publications

Improving Arthroplasty Efficiency and Quality Through Concentrating Service Volume by Complexity: Surviving the Medicare Policy Changes.

J Arthroplasty 2021 Apr 20. Epub 2021 Apr 20.

Department of Orthopaedic Surgery, Brigham and Women's Health, Boston, MA.

We have an academic medical center (AMC), an associated community-based hospital (CBH) and several ambulatory care centers which are being prepared to provide same day discharge (SDD) total joint arthroplasty (TJA) and unicompartmental knee arthroplasty (UKA). The near-capacity AMC cared for medically and technically complicated TJA patients. The CBH wanted to increase volume, improve margins, and become a center of excellence with an efficient hospital outpatient department and SDD TJA experience.

Methods: We transitioned primary, uncomplicated TJA, UKA, and minimally invasive TJA to the CBH. Revision surgeries, patients with extensive comorbidities, and complex primaries were performed at the AMC. Protocols were developed to facilitate SDD UKA and total hip arthroplasty (THA) as well as rapid recovery protocols for total knee arthroplasty (TKA) at both hospitals. A protocol-based system was put in place to make both hospitals ready for the removal of TKA from the Inpatient-Only list to avoid Quality Improvement Organization and possible resultant Recovery Audit Contractor audits if referred after implementation.

Results: The CBH volume increased 36.7% (+239). AMC volume slightly decreased (-0.46%, -5) resulting in an increase in margin contribution for the system. CBH quality metrics (surgical site infections, length of stay, readmissions, and mortality) were improved. Surgeon satisfaction improved as their volume, efficiency, quality metrics, and finances were enhanced. Although CBH per case revenue was 80.3% and 74.4% of the AMC for THA and TKA, net margins were 3.6% and 18.8% higher for THA and TKA, respectively. Increased efficiency, lower hospital cost, and higher volume at the CBH allowed for an increase in revenue despite lower reimbursement per case.

Conclusion: This strategy will help hospital systems improve net margins while improving patient care despite lower net revenue per TJA episode. These strategies will become increasingly important going forward with the transition of higher numbers of TJA patients to outpatient which will be subjected to further decreases in net revenue per patient.
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http://dx.doi.org/10.1016/j.arth.2021.04.005DOI Listing
April 2021

Classification of Skin Disease Using Deep Learning Neural Networks with MobileNet V2 and LSTM.

Sensors (Basel) 2021 Apr 18;21(8). Epub 2021 Apr 18.

School of Science, Edith Cowan University, Joondalup 6027, Australia.

Deep learning models are efficient in learning the features that assist in understanding complex patterns precisely. This study proposed a computerized process of classifying skin disease through deep learning based MobileNet V2 and Long Short Term Memory (LSTM). The MobileNet V2 model proved to be efficient with a better accuracy that can work on lightweight computational devices. The proposed model is efficient in maintaining stateful information for precise predictions. A grey-level co-occurrence matrix is used for assessing the progress of diseased growth. The performance has been compared against other state-of-the-art models such as Fine-Tuned Neural Networks (FTNN), Convolutional Neural Network (CNN), Very Deep Convolutional Networks for Large-Scale Image Recognition developed by Visual Geometry Group (VGG), and convolutional neural network architecture that expanded with few changes. The HAM10000 dataset is used and the proposed method has outperformed other methods with more than 85% accuracy. Its robustness in recognizing the affected region much faster with almost 2× lesser computations than the conventional MobileNet model results in minimal computational efforts. Furthermore, a mobile application is designed for instant and proper action. It helps the patient and dermatologists identify the type of disease from the affected region's image at the initial stage of the skin disease. These findings suggest that the proposed system can help general practitioners efficiently and effectively diagnose skin conditions, thereby reducing further complications and morbidity.
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http://dx.doi.org/10.3390/s21082852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074091PMC
April 2021

Cardiomyocyte-Specific COMMD1 Deletion Suppresses Ischemia-Induced Myocardial Apoptosis.

Cardiovasc Toxicol 2021 Apr 26. Epub 2021 Apr 26.

Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, China.

Copper metabolism MURR domain 1 (COMMD1) increases in ischemic myocardium along with suppressed contractility. Cardiomyocyte-specific deletion of COMMD1 preserved myocardial contractile function in response to the same ischemic insult. This study was undertaken to test the hypothesis that cardiomyocyte protection in COMMD1 myocardium is responsible for the functional preservation of the heart in response to ischemic insult. After ischemic insult, there were significantly more cardiomyocytes in the cardiomyocyte-specific COMMD1 deletion myocardium than that in WT controls. This preservation of cardiomyocytes was paralleled by a significant suppression of apoptosis in the COMMD1 deletion myocardium compared to controls. In searching for the mechanistic understanding of the anti-apoptotic effect of COMMD1 deletion, we found the anti-apoptotic Bcl-2 mRNA and protein expression were upregulated and the pro-apoptotic Bax mRNA and protein expression were downregulated. The critical transcription factor RelA, maintaining a high ratio between Bcl-2 and Bax for anti-apoptotic action, was suppressed by ischemia, but was rescued in the COMMD1 deletion myocardium. Because COMMD1 is critically involved in RelA ubiquitination and degradation, the data obtained here demonstrate that COMMD1 deletion leads to RelA preservation in ischemic myocardium, promoting the Bcl-2 anti-apoptotic pathway and suppressing the Bax pro-apoptotic pathway, and in combination, leading to protection of cardiomyocytes from ischemia-induced apoptosis.
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http://dx.doi.org/10.1007/s12012-021-09650-5DOI Listing
April 2021

Cancer and stem cells.

Exp Biol Med (Maywood) 2021 Apr 5:15353702211005390. Epub 2021 Apr 5.

Regenerative Medicine Research Center, Sichuan University West China Hospital, Sichuan 610041, China.

Being the second leading cause of death globally, cancer has been a long-standing and rapidly evolving focus of biomedical research and practice in the world. A tremendous effort has been made to understand the origin of cancer cells, the formation of cancerous tissues, and the mechanism by which they spread and relapse, but the disease still remains mysterious. Here, we made an attempt to scrutinize evidences that indicate the role of stem cells in tumorigenesis and metastasis, and cancer relapse. We also looked into the influence of cancers on stem cells, which in turn represent a major constituent of tumor microenvironment. Based on current understandings of the properties of (cancer) stem cells and their relation to cancers, we can foresee that novel therapeutic approaches would become the next wave of cancer treatment.
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http://dx.doi.org/10.1177/15353702211005390DOI Listing
April 2021

Trends and Complications in Spinopelvic Fixation for Deformity for Spinal Surgeons in Early Independent Practice.

Clin Spine Surg 2021 Mar 29. Epub 2021 Mar 29.

Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Study Design: Retrospective case series study.

Objective: Evaluate trends and complications following posterior spinal instrumented fusion for deformity with/without pelvic fixation using the American Board of Orthopaedic Surgery Part II Oral Examination Candidate Case List data from 2008 to 2017.

Summary Of Background Data: Complication rates for cases with pelvic fixation are widely reported in spine deformity literature but are typically derived from practices of senior surgeons. As surgical experience and clinical volume are shown to decrease complication rates, spine surgeons newly in practice may have higher risks of such events.

Materials And Methods: Surgical cases submitted by candidates taking the American Board of Orthopaedic Surgery Part II Oral Examination between 2008 and 2017 with a self-designated sub-specialty of spine surgery were retrospectively reviewed. Mortality, readmission/reoperation data, and complications as reported by candidates were tracked over time. Bivariate testing and multivariable Poisson analyses, respectively, were used to assess complication rates and time-related trends.

Results: A total of 37,539 cases were submitted between 2008 and 2017. Four hundred sixty-one cases (1.2%) were for deformity; of these, 60 cases included pelvic fixation (13% of deformity cases). For all deformity cases, we noted medical, surgical, and overall complication rates to be 17%, 22.3%, and 31.5%. Multivariable analyses demonstrated no difference in surgical/overall complication rates between spinopelvic and nonspinopelvic instrumented groups, but showed a consistently low number of cases using spinopelvic fixation over time.

Conclusions: Newly practicing spinal surgeons consistently performed low numbers of deformity cases with relatively high complication rates which remained stable over time.
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http://dx.doi.org/10.1097/BSD.0000000000001163DOI Listing
March 2021

Multifocal nodular steatosis mimicking malignancy.

Postgrad Med J 2021 Mar 29. Epub 2021 Mar 29.

Gastroenterology, James Paget University Hospitals NHS Foundation Trust, Great Yarmouth, UK.

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http://dx.doi.org/10.1136/postgradmedj-2021-139915DOI Listing
March 2021

Rare Endobronchial Polyps Due to SARS-CoV-2 Infection.

J Bronchology Interv Pulmonol 2021 Apr;28(2):e31-e33

Department of Internal Medicine, Division of Pulmonary & Critical Care Medicine Nassau University Medical Center East Meadow, NY.

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http://dx.doi.org/10.1097/LBR.0000000000000720DOI Listing
April 2021

The Association of Suppressed Hypoxia-Inducible Factor-1 Transactivation of Angiogenesis With Defective Recovery From Cerebral Ischemic Injury in Aged Rats.

Front Aging Neurosci 2021 26;13:648115. Epub 2021 Feb 26.

Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.

Elderly patients suffer more brain damage in comparison with young patients from the same ischemic stroke. The present study was undertaken to test the hypothesis that suppressed hypoxia-inducible factor-1 (HIF-1) transcription activity is responsible for defective recovery after ischemic stroke in the elders. Aged and young rats underwent 1-h transient middle cerebral artery occlusion (MCAO) to produce cerebral ischemic injury. The initial cerebral infarct volume in the young gradually declined as time elapsed, but in the aged rats remained the same. The defective recovery in the aged was associated with depressed angiogenesis and retarded neurorestoration. There was no difference in HIF-1α accumulation in the brain between the two age groups, but the expression of HIF-1 regulated genes involved in cerebral recovery was suppressed in the aged. In confirmation, inhibition of HIF-1 transactivation of gene expression in the young suppressed cerebral recovery from MCAO as the same as that observed in the aged rats. Furthermore, a copper metabolism MURR domain 1 (COMMD1) was significantly elevated after MCAO only in the brain of aged rats, and suppression of COMMD1 by siRNA targeting COMMD1 restored HIF-1 transactivation and improved recovery from MCAO-induced damage in the aged brain. These results demonstrate that impaired HIF-1 transcription activity, due at least partially to overexpression of COMMD1, is associated with the defective cerebral recovery from ischemic stroke in the aged rats.
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http://dx.doi.org/10.3389/fnagi.2021.648115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953721PMC
February 2021

Correction to: ISSLS prize in basic science 2021: a novel inducible system to regulate transgene expression of TIMP1.

Eur Spine J 2021 Mar 7. Epub 2021 Mar 7.

Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

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http://dx.doi.org/10.1007/s00586-021-06783-7DOI Listing
March 2021

Dietary Cholesterol Supplements Disturb Copper Homeostasis in Multiple Organs in Rabbits: Aorta Copper Concentrations Negatively Correlate with the Severity of Atherosclerotic Lesions.

Biol Trace Elem Res 2021 Mar 4. Epub 2021 Mar 4.

Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Dietary cholesterol causes atherosclerosis along with a reduction of copper concentrations in the atherosclerosis wall. This study was to determine the relationship between aorta copper concentrations and the severity of atherosclerotic lesions as well as copper homeostasis in multiple organs in cholesterol-fed rabbits. Male New Zealand white rabbits, 10-week-old and averaged 2.0 kg, were fed a diet containing 1% (w/w) cholesterol or the same diet without cholesterol as controls. Twelve weeks after the feeding, aortic atherosclerotic lesions, serum cholesterol, and multiple organ copper concentrations were measured. Compared to controls, rabbits fed cholesterol-supplemented diet displayed higher serum cholesterol levels and developed atherosclerosis. Copper concentrations in the cholesterol-fed rabbits were increased in the serum and kidney but decreased in the atherosclerosis wall and multiple organs, including heart, liver, spleen, and lung. Furthermore, aorta copper concentrations negatively correlated, respectively, with the severity of the atherosclerotic lesion (r = - 0.64, p = 0.01), the microscope atherosclerotic lesion area (r = - 0.60, p = 0.02), and the stenosis of the lumen (r = - 0.54, p = 0.04). Dietary cholesterol not only causes atherosclerosis but also disturbs copper homeostasis in multiple organ systems. The negative correlation between aorta copper concentrations and the severity of atherosclerotic lesions suggests a vicious cycle between copper reduction and the pathogenesis of atherosclerosis. These changes in copper homeostasis would be additive to atherosclerosis as a risk factor for cardiovascular disease in humans.
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http://dx.doi.org/10.1007/s12011-021-02618-0DOI Listing
March 2021

COMMD1 upregulation is involved in copper efflux from ischemic hearts.

Exp Biol Med (Maywood) 2021 Mar 6;246(5):607-616. Epub 2020 Dec 6.

Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China.

Copper depletion is associated with myocardial ischemic infarction, in which copper metabolism MURR domain 1 (COMMD1) is increased. The present study was undertaken to test the hypothesis that the elevated COMMD1 is responsible for copper loss from the ischemic myocardium, thus worsening myocardial ischemic injury. Mice (C57BL/6J) were subjected to left anterior descending coronary artery permanent ligation to induce myocardial ischemic infarction. In the ischemic myocardium, copper reduction was associated with a significant increase in the protein level of COMMD1. A tamoxifen-inducible, cardiomyocyte -specific knockout mouse (C57BL/6J) model () was generated using the recombination system. and wild-type littermates were subjected to the same permanent ligation of left anterior descending coronary artery. At the 7th day after ischemic insult, COMMD1 deficiency suppressed copper loss in the heart, along with preservation of vascular endothelial growth factor and vascular endothelial growth factor receptor 1 expression and the integrity of the vascular system in the ischemic myocardium. Corresponding to this change, infarct size of ischemic heart was reduced and myocardial contractile function was well preserved in mice. These results thus demonstrate that upregulation of COMMD1 is at least partially responsible for copper efflux from the ischemic heart. Cardiomyocyte-specific deletion of COMMD1 helps preserve the availability of copper for angiogenesis, thus suppressing myocardial ischemic dysfunction.
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http://dx.doi.org/10.1177/1535370220969844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934151PMC
March 2021

Nerve injury alters restraint-induced activation of the basolateral amygdala in male rats.

Brain Struct Funct 2021 May 13;226(4):1209-1227. Epub 2021 Feb 13.

Faculty of Medicine and Health, School of Medical Sciences (Neuroscience), The University of Sydney, Sydney, NSW, 2006, Australia.

The amygdala is critical for the production of appropriate responses towards emotional or stressful stimuli. It has a characteristic neuronal activation pattern to acute stressors. Chronic pain and acute stress have each been shown to independently modulate the activity of the amygdala. Few studies have investigated the effect of pain or injury, on amygdala activation to acute stress. This study investigated the effects of a neuropathic injury on the activation response of the amygdala to an acute restraint stress. Chronic constriction injury of the right sciatic nerve (CCI) was used to create neuropathic injury and a single brief 15-min acute restraint was used as an emotional/psychological stressor. All rats received cholera toxin B (CTB) retrograde tracer injections into the medial prefrontal cortex (mPFC) to assess if the amygdala to mPFC pathway was specifically regulated by the combination of neuropathic injury and acute stress. To assess differential patterns of activity in amygdala subregions, cFos expression was used as a marker for "acute", restraint triggered neuronal activation, and FosB/ΔFosB expression was used to reveal prolonged neuronal activation/sensitisation triggered by CCI. Restraint resulted in a characteristic increase in cFos expression in the medial amygdala, which was not altered by CCI. Rats with a CCI showed increased cFos expression in the basolateral amygdala (BLA), in response to an acute restraint stress, but not in neurons projecting to the prefrontal cortex. Further, CCI rats showed an increase in FosB/ΔFosB expression which was exclusive to the BLA. This increase likely reflects sensitisation of the BLA as a consequence of nerve injury which may contribute to heightened sensitivity of BLA neurons to acute emotional/ psychological stressors.
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http://dx.doi.org/10.1007/s00429-021-02235-6DOI Listing
May 2021

ISSLS prize in basic science 2021: a novel inducible system to regulate transgene expression of TIMP1.

Eur Spine J 2021 Feb 1. Epub 2021 Feb 1.

Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Purpose: Inflammatory and oxidative stress upregulates matrix metalloproteinase (MMP) activity, leading to intervertebral disc degeneration (IDD). Gene therapy using human tissue inhibitor of metalloproteinase 1 (hTIMP1) has effectively treated IDD in animal models. However, persistent unregulated transgene expression may have negative side effects. We developed a recombinant adeno-associated viral (AAV) gene vector, AAV-NFκB-hTIMP1, that only expresses the hTIMP1 transgene under conditions of stress.

Methods: Rabbit disc cells were transfected or transduced with AAV-CMV-hTIMP1, which constitutively expresses hTIMP1, or AAV-NFκB-hTIMP1. Disc cells were selectively treated with IL-1β. NFκB activation was verified by nuclear translocation. hTIMP1 mRNA and protein expression were measured by RT-PCR and ELISA, respectively. MMP activity was measured by following cleavage of a fluorogenic substrate.

Results: IL-1β stimulation activated NFκB demonstrating that IL-1β was a surrogate for inflammatory stress. Stimulating AAV-NFκB-hTIMP1 cells with IL-1β increased hTIMP1 expression compared to unstimulated cells. AAV-CMV-hTIMP1 cells demonstrated high levels of hTIMP1 expression regardless of IL-1β stimulation. hTIMP1 expression was comparable between IL-1β stimulated AAV-NFκB-hTIMP1 cells and AAV-CMV-hTIMP1 cells. MMP activity was decreased in AAV-NFκB-hTIMP1 cells compared to baseline levels or cells exposed to IL-1β.

Conclusion: AAV-NFκB-hTIMP1 is a novel inducible transgene delivery system. NFκB regulatory elements ensure that hTIMP1 expression occurs only with inflammation, which is central to IDD development. Unlike previous inducible systems, the AAV-NFκB-hTIMP1 construct is dependent on endogenous factors, which minimizes potential side effects caused by constitutive transgene overexpression. It also prevents the unnecessary production of transgene products in cells that do not require therapy.
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http://dx.doi.org/10.1007/s00586-021-06728-0DOI Listing
February 2021

An Energy-Efficient and Secure Data Inference Framework for Internet of Health Things: A Pilot Study.

Sensors (Basel) 2021 Jan 5;21(1). Epub 2021 Jan 5.

Department of Computing, Macquarie University, Sydney 2109, Australia.

Privacy protection in electronic healthcare applications is an important consideration, due to the sensitive nature of personal health data. Internet of Health Things (IoHT) networks that are used within a healthcare setting have unique challenges and security requirements (integrity, authentication, privacy, and availability) that must also be balanced with the need to maintain efficiency in order to conserve battery power, which can be a significant limitation in IoHT devices and networks. Data are usually transferred without undergoing filtering or optimization, and this traffic can overload sensors and cause rapid battery consumption when interacting with IoHT networks. This poses certain restrictions on the practical implementation of these devices. In order to address these issues, this paper proposes a privacy-preserving two-tier data inference framework solution that conserves battery consumption by inferring the sensed data and reducing data size for transmission, while also protecting sensitive data from leakage to adversaries. The results from experimental evaluations on efficiency and privacy show the validity of the proposed scheme, as well as significant data savings without compromising data transmission accuracy, which contributes to energy efficiency of IoHT sensor devices.
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http://dx.doi.org/10.3390/s21010312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796504PMC
January 2021

Conditioned open-label placebo for opioid reduction after spine surgery: a randomized controlled trial.

Pain 2021 Jan 11. Epub 2021 Jan 11.

Departments of Anesthesiology, Perioperative, and Pain Medicine and Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States Program in Placebo Studies and Therapeutic Encounter, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.

Abstract: Placebo effects have traditionally involved concealment or deception. However, recent evidence suggests that placebo effects can also be elicited when prescribed transparently as "open-label placebos" (OLPs), and that the pairing of an unconditioned stimulus (eg, opioid analgesic) with a conditioned stimulus (eg, placebo pill) can lead to the conditioned stimulus alone reducing pain. In this randomized control trial, we investigated whether combining conditioning with an OLP (COLP) in the immediate postoperative period could reduce daily opioid use and postsurgical pain among patients recovering from spine surgery. Patients were randomized to COLP or treatment as usual, with both groups receiving unrestricted access to a typical opioid-based postoperative analgesic regimen. The generalized estimating equations method was used to assess the treatment effect of COLP on daily opioid consumption and pain during postoperative period from postoperative day (POD) 1 to POD 17. Patients in the COLP group consumed approximately 30% less daily morphine milligram equivalents compared with patients in the treatment as usual group during POD 1 to 17 (-14.5 daily morphine milligram equivalents; 95% CI: [-26.8, -2.2]). Daily worst pain scores were also lower in the COLP group (-1.0 point on the 10-point scale; 95% CI: [-2.0, -0.1]), although a significant difference was not detected in average daily pain between the groups (-0.8 point; 95% CI: [-1.7, 0.2]). These findings suggest that COLP may serve as a potential adjuvant analgesic therapy to decrease opioid consumption in the early postoperative period, without increasing pain.
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http://dx.doi.org/10.1097/j.pain.0000000000002185DOI Listing
January 2021

Orthopaedic Manifestations of Amyloidosis.

J Am Acad Orthop Surg 2021 May;29(10):e488-e496

From the Department of Orthopaedic Surgery, Brigham and Women's Hospital, Boston, MA (Zhang, Makhni, Kang, and Blazar), and the Harvard Medical School, Boston, MA (Zhang, Makhni, Kang, and Blazar).

Amyloidosis is a disorder of misfolded proteins in human tissues, which can result in morbid cardiac and neurological disease. Historically, the utility of tissue biopsy during orthopaedic procedures to detect amyloidosis has been limited because no disease-modifying therapies were available; however, new drug therapies have recently emerged for the treatment of amyloidosis. Although these novel pharmaceuticals show promise for slowing disease progression, they are primarily effective in the early stages of amyloidosis, underscoring the importance of early diagnosis. Common orthopaedic manifestations of amyloidosis include carpal tunnel syndrome, trigger finger, spontaneous distal biceps tendon rupture, rotator cuff disease, and lumbar spinal stenosis. Carpal tunnel syndrome is frequently the earliest manifestation of amyloidosis, on average preceding a formal diagnosis of amyloidosis by over four years. By recognizing the constellation of musculoskeletal symptoms in the patient with amyloidosis, orthopaedic surgeons can play an active role in patient referral, early detection of systemic disease, and prompt initiation of disease-modifying treatment. There may be a role for selective biopsy for amyloid deposition in at-risk patients during routine orthopaedic procedures.
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http://dx.doi.org/10.5435/JAAOS-D-20-01146DOI Listing
May 2021

Editorial: From the Editor-in-Chief.

Authors:
Y James Kang

Cardiovasc Toxicol 2021 Jan 2;21(1). Epub 2021 Jan 2.

Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, China.

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http://dx.doi.org/10.1007/s12012-020-09628-9DOI Listing
January 2021

Reverse regulation of hepatic ceruloplasmin production in rat model of myocardial ischemia.

J Trace Elem Med Biol 2021 Mar 16;64:126686. Epub 2020 Nov 16.

Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, 610041, China. Electronic address:

Background: Ceruloplasmin (Cp) is a major copper-binding protein produced in the liver and delivers copper to extrahepatic organs. Patients with myocardial infarction are often featured by an elevation of serum copper concentrations due to copper efflux from ischemic hearts. The present study was undertaken to test the hypothesis that serum copper elevation leads to up-regulation of hepatic Cp in myocardial infarction.

Methods: Adult male Sprague-Dawley rats were subjected to left anterior descending (LAD) coronary artery ligation to induce myocardial infarction. Serum copper and Cp levels, as well as changes in hepatic Cp and copper-transporting P-type ATPase (Atp7b), were determined from blood and liver samples collected on day 1, 4, or 7 after the operation.

Results: Serum copper concentrations were significantly increased on day 4 after LAD ligation, accompanied by an increase in serum Cp levels and activities. Concomitantly, the protein levels of Cp and copper exporter, Atp7b, were also significantly increased in the liver. Furthermore, inhibiting the increase of serum copper by a copper chelator, triethylenetetramine (TETA), effectively abolished the elevated Cp activity after LAD ligation.

Conclusion: These results indicate that serum Cp elevation in response to myocardial ischemia most likely resulted from the increased hepatic Cp production, which in turn was more responsive to serum copper elevation than inflammatory response following myocardial ischemia.
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http://dx.doi.org/10.1016/j.jtemb.2020.126686DOI Listing
March 2021

National utilization and inpatient safety measures of lumbar spinal fusion methods by race/ethnicity.

Spine J 2020 Nov 20. Epub 2020 Nov 20.

Harvard Medical School, 25 Shattuck St, Boston, MA 02115 USA; Division of General Medicine, Massachusetts General Hospital, 50 Staniford St, 9th floor, Boston, MA 02114 USA.

Background Context: Degenerative lumbar conditions are prevalent, disabling, and frequently managed with decompression and fusion. Black patients have lower spinal fusion rates than White patients.

Purpose: Determine whether specific lumbar fusion procedure utilization differs by race/ethnicity and whether length of stay (LOS) or inpatient complications differ by race/ethnicity after accounting for procedure performed.

Study Design: Large database retrospective cohort study PATIENT SAMPLE: Lumbar fusion recipients at least age 50 in the 2016 National Inpatient Sample with diagnoses of degenerative lumbar conditions.

Outcome Measures: Type of fusion procedure used and inpatient safety measures including LOS, prolonged LOS, inpatient medical and surgical complications, mortality, and cost.

Methods: We examined the association between race/ethnicity and the safety measures above. Covariates included several patient and hospital factors. We used multiple linear or logistic regression to determine the association between race and fusion type (PLF, P/TLIF, ALIF, PLF + P/TLIF, and PLF + ALIF [anterior-posterior fusion]) and to determine whether race was associated independently with inpatient safety measures, after adjustment for patient and hospital factors.

Results: Fusion method use did not differ among racial/ethnic groups, except for somewhat lower anterior-posterior fusion utilization in Black patients compared to White patients (crude odds ratio [OR]: 0.81 [0.67-0.97]). Inpatient safety measures differed by race/ethnicity for rates of prolonged LOS (Blacks 18.1%, Hispanics 14.5%, and Whites 11.7%), medical complications (Blacks 9.9%, Hispanics 8.7%, and Whites 7.7%), and surgical complications (Blacks 5.2%, Hispanics 6.9%, and Whites 5.4%). Differences persisted after adjustment for procedure type as well as patient and hospital factors. Blacks and Hispanics had higher risk for prolonged LOS compared to Whites (adjusted OR Blacks 1.39 [95% confidence interval {CI} 1.22-1.59]; Hispanics 1.24 [95% CI 1.02-1.52]). Blacks had higher risk for inpatient medical complications compared to Whites (adjusted OR 1.24 [95% CI 1.05-1.48]), and Hispanics had higher risk for inpatient surgical complications compared to Whites (adjusted OR 1.34 [95% CI 1.06-1.68]).

Conclusions: Fusion method use was generally similar between racial/ethnic groups. Inpatient safety measures, adjusted for procedure type, patient and hospital factors, were worse for Blacks and Hispanics.
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http://dx.doi.org/10.1016/j.spinee.2020.11.003DOI Listing
November 2020

Mitophagy promotes the stemness of bone marrow-derived mesenchymal stem cells.

Exp Biol Med (Maywood) 2021 01 10;246(1):97-105. Epub 2020 Nov 10.

Regenerative Medicine Research Center, West China Hospital, Sichuan University, Sichuan, 610041, China.

Previous studies demonstrated that mitochondrial fission arguments the stemness of bone marrow-derived mesenchymal stem cells (BMSCs). Because mitophagy is critical in removing damaged or surplus mitochondrial fragments and maintaining mitochondrial integrity, the present study was undertaken to test the hypothesis that mitophagy is involved in mitochondrial fission-enhanced stemness of BMSCs. Primary cultures of rat BMSCs were treated with tyrphostin A9 (TA9, a potent inducer of mitochondrial fission) to increase mitochondrial fission, which was accompanied by enhanced mitophagy as defined by increased co-staining of MitoTracker Green for mitochondria and LysoTracker Deep Red for lysosomes, as well as the increased co-localization of autophagy markers (LC3B, P62) and mitochondrial marker (Tom20). A mitochondrial uncoupler, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) was used to promote mitophagy, which was confirmed by an increased co-localization of mitochondrial and lysosome biomarkers. The argumentation of mitophagy was associated with enhanced stemness of BMSCs as defined by increased expression of stemness markers Oct4 and Sox2, and enhanced induction of BMSCs to adipocytes or osteocytes. Conversely, transfection of BMSCs with siRNA targeting mitophagy-essential genes / led to diminished stemness of the stem cells, as defined by depressed stemness markers. Importantly, concomitant promotion of mitochondrial fission and inhibition of mitophagy suppressed the stemness of BMSCs. These results thus demonstrate that mitophagy is critically involved in mitochondrial fission promotion of the stemness of BMSCs.
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http://dx.doi.org/10.1177/1535370220964394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797993PMC
January 2021

Development of prediction models for clinically meaningful improvement in PROMIS scores after lumbar decompression.

Spine J 2021 Mar 31;21(3):397-404. Epub 2020 Oct 31.

Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Orthopedic Surgery, Newton Wellesley Hospital, Newton, MA, USA. Electronic address:

Background: The ability to preoperatively predict which patients will achieve a minimal clinically important difference (MCID) after lumbar spine decompression surgery can help determine the appropriateness and timing of surgery. Patient-Reported Outcome Measurement Information System (PROMIS) scores are an increasingly popular outcome instrument.

Purpose: The purpose of this study was to develop algorithms predictive of achieving MCID after primary lumbar decompression surgery.

Patient Sample: This was a retrospective study at two academic medical centers and three community medical centers including adult patients 18 years or older undergoing one or two level posterior decompression for lumbar disc herniation or lumbar spinal stenosis between January 1, 2016 and April 1, 2019.

Outcome Measures: The primary outcome, MCID, was defined using distribution-based methods as one half the standard deviation of postoperative patient-reported outcomes (PROMIS physical function, pain interference, pain intensity).

Methods: Five machine learning algorithms were developed to predict MCID on these surveys and assessed by discrimination, calibration, Brier score, and decision curve analysis. The final model was incorporated into an open access digital application.

Results: Overall, 906 patients completed at least one PROMs survey in the 90 days before surgery and at least one PROMs survey in the year after surgery. Attainment of MCID during the study period by PROMIS instrument was 74.3% for physical function, 75.8% for pain interference, and 79.2% for pain intensity. Factors identified for preoperative prediction of MCID attainment on these outcomes included preoperative PROs, percent unemployment in neighborhood of residence, comorbidities, body mass index, private insurance, preoperative opioid use, surgery for disc herniation, and federal poverty level in neighborhood of residence. The discrimination (c-statistic) of the final algorithms for these outcomes was 0.79 for physical function, 0.74 for pain interference, and 0.69 for pain intensity with good calibration. The open access digital application for these algorithms can be found here: https://sorg-apps.shinyapps.io/promis_pld_mcid/ CONCLUSION: Lower preoperative PROMIS scores, fewer comorbidities, and certain sociodemographic factors increase the likelihood of achieving MCID for PROMIS after lumbar spine decompression.
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http://dx.doi.org/10.1016/j.spinee.2020.10.026DOI Listing
March 2021

Controlling the Poly(ε-caprolactone) Degradation to Maintain the Stemness and Function of Adipose-Derived Mesenchymal Stem Cells in Vascular Regeneration Application.

Macromol Biosci 2021 01 22;21(1):e2000226. Epub 2020 Oct 22.

S. Yang, Dr. X. Jiang, X. Xiao, C. Niu, Y. Xu, Z. Huang, Prof. Y. J. Kang, Prof. L. Feng, Regenerative Medicine Research Center, Sichuan University West China Hospital, No. 4 Keyuan Road, Wuhou District, Chengdu, 610041, China.

Biodegradable poly(ε-caprolactone) (PCL) scaffolds with adipose-derived mesenchymal stem cells (ADSCs) have been used in vascular regeneration studies. An evaluation method of the effect of PCL degradation products (DP) on the viability, stemness, and differentiation capacities of ADSCs is established. ADSCs are cultured in medium containing different concentrations of PCL DP before evaluating the effect of PCL DP on the cell apoptosis and proliferation, cell surface antigens, adipogenic and osteogenic differentiation capacities, and capacities to differentiate into endothelial cells and smooth muscle cells. The results demonstrate that PCL DP exceed 0.05 mg mL may change the stemness and differentiation capacities of ADSCs. Therefore, to control the proper concentration of PCL DP is essential for ADSCs in vascular regeneration application.
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http://dx.doi.org/10.1002/mabi.202000226DOI Listing
January 2021

Surgeon-level variance in achieving clinical improvement after lumbar decompression: the importance of adequate risk adjustment.

Spine J 2021 Mar 9;21(3):405-410. Epub 2020 Oct 9.

Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Orthopaedic Surgery, Newton Wellesley Hospital, Newton, MA 02462, USA. Electronic address:

Background Context: Patient-Reported Outcome Measurement Information System (PROMIS) scores are increasingly utilized in clinical care. However, it is unclear if PROMIS can discriminate surgeon performance on an individual level.

Purpose: The purpose of this study was to examine surgeon-level variance in rates of achieving minimal clinically important difference (MCID) after lumbar decompression.

Patient Sample: This is a prospective, observational cohort study performed across a healthcare enterprise (two academic medical centers and three community centers). Patients 18 years or older undergoing one- to two-level primary decompression for lumbar disc herniation (LDH) or lumbar spinal stenosis (LSS) were included.

Outcome Measures: The primary outcome was achievement of MCID, using a distribution-based method, on paired PROMIS physical function scores.

Methods: Descriptive statistics were generated to examine the baseline characteristics of the study cohort. Bivariate analyses were used to examine the impact of surgeon-level variance on rates of MCID. Multivariable analyses were used to examine the risk-adjusted impact of surgeon-level variance on rates of MCID.

Results: Overall, 636 patients treated by nine surgeons were included. The median patient age was 58 [interquartile range (IQR): 46-70] and 62.3% (n=396) were female. Among all patients, 56.9% (n=362) underwent surgery for LDH. The overall rate of achieving MCID was 75.8% (n=482). Of the surgeons, the median years in practice were 12 (range 4-31) and 55.6% (n=5) were in academic practice settings. On bivariate analysis, patients treated by one of the surgeons had lower rates of achieving MICD (odds ratio=0.37, 95% confidence interval: 0.15-0.91, p=.03). However, on multivariable analysis adjusting for operative indication (LDH vs. LSS), body mass index, number of comorbidities, percent unemployment in patient zip code, and preoperative PROMIS physical function scores, all surgeons were equally likely to obtain MCID.

Conclusions: In this cohort, variance in PROMIS scores after primary lumbar decompression is influenced by patient-related factors and not by individual surgeon. Adequate risk adjustment is needed if ascertaining clinical improvement on an individual surgeon basis.

Level Of Evidence: 2.
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http://dx.doi.org/10.1016/j.spinee.2020.10.005DOI Listing
March 2021

Complication Events After Spinal Surgery Performed by American Board of Orthopaedic Surgery (ABOS) Part II Candidates (2008-2017).

Spine (Phila Pa 1976) 2021 Jan;46(2):101-106

Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Study Design: Retrospective cohort study.

Objective: To evaluate complications following spine surgery using American Board of Orthopaedic Surgeons (ABOS) Part II examination data from 2008 to 2017.

Summary Of Background Data: Recent research has demonstrated the importance of surgical experience and clinical volume in minimizing complications after spine surgery. This may be challenging for orthopedic spine surgeons who are just starting their practice.

Methods: We performed a retrospective review of surgical cases submitted to the ABOS by candidates taking the Part II Spine examination between 2008 and 2017. Complications, including peri-operative mortality as reported by candidates to the ABOS, were tracked over time. Complications were classified as surgical or medical using a predefined algorithm. Multivariable Poisson regression analyses adjusting for confounders were used to assess rates of complications and mortality over time. All analyses controlled for biologic sex, age, surgical diagnosis, and surgical location.

Results: A total of 37,539 spine surgical patients were analyzed, with an average of 3754 cases performed each year. Following adjusted Poisson analysis, we determined that cases in 2017 had an increased likelihood of complications when compared to those treated in 2008 (IRR 1.20; 95% CI 1.09, 1.32). Similar findings were encountered for surgical complications (IRR 1.20; 95% CI 1.07, 1.34). In contrast, spine surgical cases reported to the ABOS in 2017 had a 55% lower likelihood of mortality when compared to procedures performed in 2008 (IRR 0.45; 95% CI 0.24, 0.84; P = 0.01).

Conclusions: Our analysis of ABOS Part II candidates demonstrates that reported complication rates may be increasing while mortality is decreasing. The etiologies behind these findings are likely multifactorial. Encouragingly, we believe that observed reductions in mortality suggest overall improvements in patient safety following spine surgery. At a minimum, our data provide benchmarks through which spine surgeons, hospitals, and residency or fellowship programs can evaluate performance.Level of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000003741DOI Listing
January 2021

In vitro nucleus pulposus tissue model with physicochemical stresses.

JOR Spine 2020 Sep 1;3(3):e1105. Epub 2020 Jul 1.

Department of Orthopaedic Surgery Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts USA.

Intervertebral discs (IVDs) are exposed to changes in physicochemical stresses including hydrostatic and osmotic pressure via diurnal spinal motion. Homeostasis, degeneration, and regeneration in IVDs have been studied using in vitro, ex vivo, and animal models. However, incubation of nucleus pulposus (NP) cells in medium has limited capability to reproduce anabolic turnover and regeneration under physicochemical stresses. We developed a novel pressure/perfusion cell culture system and a semipermeable membrane pouch device for enclosing isolated NP cells for in vitro incubation under physicochemical stresses. We assessed the performance of this system to identify an appropriate stress loading regimen to promote gene expression and consistent accumulation of extracellular matrices by bovine caudal NP cells. Cyclic hydrostatic pressure (HP) for 4 days followed by constant HP for 3 days in high osmolality (HO; 450 mOsm/kg HO) showed a trend towards upregulated aggrecan expression and dense accumulation of keratan sulfate without gaps by the NP cells. Furthermore, a repetitive regimen of cyclic HP for 2 days followed by constant HP for 1 day in HO (repeated twice) significantly upregulated gene expression of aggrecan ( < .05) compared to no pressure and suppressed matrix metalloproteinase-13 expression ( < .05) at 6 days. Our culture system and pouches will be useful to reproduce physicochemical stresses in NP cells for simulating anabolic, catabolic, and homeostatic turnover under diurnal spinal motion.
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http://dx.doi.org/10.1002/jsp2.1105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524234PMC
September 2020

Can unrecognized fecal loading without infrequent bowel movements be a cause of symptoms in a subset of patients with functional bowel disorders?

Indian J Gastroenterol 2020 Sep 19. Epub 2020 Sep 19.

Department of Medicine, National University of Singapore, Singapore, Singapore.

Infrequent bowel movements are a common feature of constipation, but fecal loading as a cause of symptoms in patients with regular bowel movements has not previously been evaluated. The aim of this preliminary study was to assess prospectively if fecal loading may be a cause of bowel symptoms in patients with regular bowel movements. Consecutive patients attending a gastroenterology clinic for functional bowel symptoms (FBD) not including infrequent bowel movements and who did not fulfil the criteria for constipation-predominant irritable bowel syndrome or functional constipation underwent plain abdominal radiography. Those with fecal loading received dietary advice and laxative treatment. The reproducibility of determination of fecal loading using the Leech score was assessed 'blindly' by a consultant radiologist. Twenty-six of 74 patients with FBD but not infrequent bowel movements had fecal loading demonstrated on abdominal radiology. Their Leech scores were significantly higher than those of control patients matched for age, sex and hospital (median 6 vs. 4, IQR 5-7 vs. 3.5-5, p < 0.001). Three out of 20 patients (15%) who returned for review after dietary advice and laxatives were asymptomatic and 17/20 (85%) had improved. Fecal loading may therefore cause bowel symptoms in patients who move their bowels regularly and dietary and laxative treatment may then improve these symptoms. This approach may prove cost-effective as an empirical interim measure especially where healthcare resources are limited and where sophisticated imaging is not readily available.
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http://dx.doi.org/10.1007/s12664-020-01063-6DOI Listing
September 2020

Trends in Spinal Surgery Performed by American Board of Orthopaedic Surgery Part II Candidates (2008 to 2017).

J Am Acad Orthop Surg 2020 Sep 17. Epub 2020 Sep 17.

From the Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Introduction: The American Board of Orthopaedic Surgery (ABOS) Part II Oral Examination is typically taken two calendar years after fellowship completion. Despite previous studies using ABOS Part II Oral Examination data in other subspecialties, types of cases performed by spine surgeons in initial independent practice have not been well-studied. Such data may help trainees anticipate case composition observed in early practice and allow spine fellowship programs to understand emerging trends.

Methods: We retrospectively reviewed surgical cases submitted to the ABOS by candidates taking the Part II Oral Examination between 2008 and 2017 whose designated subspecialty was spine. A hierarchical, restrictive algorithm was used to determine procedures based on candidate-reported International Classification of Diseases 9th/10th Revision and Current Procedural Terminology codes. Adjusted multivariable Poisson regression analyses were used to assess changes in procedure incidence rates over time.

Results: We identified 37,539 cases, averaging 3,754 cases/yr, and an average of 49 cases per candidate per 6-month collection period. The most common procedures were lumbar diskectomy (22% of all procedures), posterolateral spinal fusion (PSF) (19%), and anterior cervical diskectomy and fusion (ACDF) (17%). Rates of ACDF and cervical disk arthroplasty significantly increased over time (incidence rate ratios of 1.41 and 23.3 times higher, respectively, at the end of the study period), whereas rates of cervical foraminotomy, lumbar diskectomy, PSF, and structural autograft use decreased (incidence rate ratios of 0.35, 0.84, 0.55, and 0.30). Rates of anterior lumbar interbody fusion/lateral lumbar interbody fusion and transforaminal lumbar interbody fusion did not significantly change over the study period.

Discussion: Recent spine fellowship graduates are performing more cervical disk arthroplasties and ACDFs while decreasingly using structural autograft as well as performing fewer PSFs and lumbar diskectomies. Techniques such as anterior lumbar interbody fusion/lateral lumbar interbody fusions and transforaminal lumbar interbody fusions have not changed significantly over the last decade.

Level Of Evidence: Level IV (retrospective case series study).
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http://dx.doi.org/10.5435/JAAOS-D-20-00437DOI Listing
September 2020

Brief Preoperative Screening for Frailty and Cognitive Impairment Predicts Delirium after Spine Surgery.

Anesthesiology 2020 12;133(6):1184-1191

Background: Frailty and cognitive impairment are associated with postoperative delirium, but are rarely assessed preoperatively. The study was designed to test the hypothesis that preoperative screening for frailty or cognitive impairment identifies patients at risk for postoperative delirium (primary outcome).

Methods: In this prospective cohort study, the authors administered frailty and cognitive screening instruments to 229 patients greater than or equal to 70 yr old presenting for elective spine surgery. Screening for frailty (five-item FRAIL scale [measuring fatigue, resistance, ambulation, illness, and weight loss]) and cognition (Mini-Cog, Animal Verbal Fluency) were performed at the time of the preoperative evaluation. Demographic data, perioperative variables, and postoperative outcomes were gathered. Delirium was the primary outcome detected by either the Confusion Assessment Method, assessed daily from postoperative day 1 to 3 or until discharge, if patient was discharged sooner, or comprehensive chart review. Secondary outcomes were all other-cause complications, discharge not to home, and hospital length of stay.

Results: The cohort was 75 [73 to 79 yr] years of age, 124 of 219 (57%) were male. Many scored positive for prefrailty (117 of 218; 54%), frailty (53 of 218; 24%), and cognitive impairment (50 to 82 of 219; 23 to 37%). Fifty-five patients (25%) developed delirium postoperatively. On multivariable analysis, frailty (scores 3 to 5 [odds ratio, 6.6; 95% CI, 1.96 to 21.9; P = 0.002]) versus robust (score 0) on the FRAIL scale, lower animal fluency scores (odds ratio, 1.08; 95% CI, 1.01 to 1.51; P = 0.036) for each point decrease in the number of animals named, and more invasive surgical procedures (odds ratio, 2.69; 95% CI, 1.31 to 5.50; P = 0.007) versus less invasive procedures were associated with postoperative delirium.

Conclusions: Screening for frailty and cognitive impairment preoperatively using the FRAIL scale and the Animal Verbal Fluency test in older elective spine surgery patients identifies those at high risk for the development of postoperative delirium.

Editor’s Perspective:
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http://dx.doi.org/10.1097/ALN.0000000000003523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657972PMC
December 2020

Transforming the Orthopaedic Patient Experience Through Telemedicine.

J Patient Exp 2020 Jun 27;7(3):302-304. Epub 2020 May 27.

Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1177/2374373520929449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410140PMC
June 2020