Publications by authors named "John Shin"

227 Publications

The effectiveness of systemic therapies after surgery for metastatic renal cell carcinoma to the spine: a propensity analysis controlling for sarcopenia, frailty, and nutrition.

J Neurosurg Spine 2021 Jun 25:1-10. Epub 2021 Jun 25.

Departments of1Neurosurgery.

Objective: The effectiveness of starting systemic therapies after surgery for spinal metastases from renal cell carcinoma (RCC) has not been evaluated in randomized controlled trials. Agents that target tyrosine kinases, mammalian target of rapamycin signaling, and immune checkpoints are now commonly used. Variables like sarcopenia, nutritional status, and frailty may impact recovery from spine surgery and are considered when evaluating a patient's candidacy for such treatments. A better understanding of the significance of these variables may help improve patient selection for available treatment options after surgery. The authors used comparative effectiveness methods to study the treatment effect of postoperative systemic therapies (PSTs) on survival.

Methods: Univariable and multivariable Cox regression analyses were performed to determine factors associated with overall survival (OS) in a retrospective cohort of adult patients who underwent spine surgery for metastatic RCC between 2010 and 2019. Propensity score-matched (PSM) analysis and inverse probability weighting (IPW) were performed to determine the treatment effect of PST on OS. To address confounding and minimize bias in estimations, PSM and IPW were adjusted for covariates, including age, sex, frailty, sarcopenia, nutrition, visceral metastases, International Metastatic RCC Database Consortium (IMDC) risk score, and performance status.

Results: In total, 88 patients (73.9% male; median age 62 years, range 29-84 years) were identified; 49 patients (55.7%) had an intermediate IMDC risk, and 29 (33.0%) had a poor IMDC risk. The median follow-up was 17 months (range 1-104 months) during which 57 patients (64.7%) died. Poor IMDC risk (HR 3.2 [95% CI 1.08-9.3]), baseline performance status (Eastern Cooperative Oncology Group score 3 or 4; HR 2.7 [95% CI 1.5-4.7]), and nutrition (prognostic nutritional index [PNI] first tertile, PNI < 40.74; HR 2.69 [95% CI 1.42-5.1]) were associated with worse OS. Sarcopenia and frailty were not significantly associated with poor survival. PST was associated with prolonged OS, demonstrated by similar effects from multivariable Cox analysis (HR 0.55 [95% CI 0.30-1.00]), PSM (HR 0.53 [95% CI 0.29-0.93]), IPW (HR 0.47 [95% CI 0.24-0.94]), and comparable confidence intervals. The median survival for those receiving PST was 28 (95% CI 19-43) months versus 12 (95% CI 4-37) months for those who only had surgery (log-rank p = 0.027).

Conclusions: This comparative analysis demonstrated that PST is associated with improved survival in specific cohorts with metastatic spinal RCC after adjusting for frailty, sarcopenia, and malnutrition. The marked differences in survival should be taken into consideration when planning for surgery.
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http://dx.doi.org/10.3171/2020.12.SPINE201896DOI Listing
June 2021

Open epidural blood patch to augment durotomy repair in lumbar spine surgery: surgical technique and cohort study.

Spine J 2021 Jun 16. Epub 2021 Jun 16.

Massachusetts General Hospital, Boston, MA. Electronic address:

Background Context: Incidental durotomy during elective spine surgery is relatively common. While usually benign and self-limited, it can be associated with morbidity, increased cost, and medicolegal ramifications. Dural repair typically involves performing a primary closure using a suture or dural staple; repairs are then frequently augmented with a sealant, patch, or fat/fascial graft. Although primary repair of an incidental durotomy is standard practice, the ideal secondary sealant or augment choice remains unclear. A wide variety of commercially available dural sealant options exist, and while none have demonstrated consistent superiority, all are associated with single-use costs in the hundreds to thousands of dollars and have concerns regarding swelling, local inflammation, or short-lived dural adherence.

Purpose: The goal of this study is to compare the results of dural repair augmentation using an open intraoperative epidural blood patch to a hydrogel technique.

Study Design/setting: Retrospective comparative cohort study at an academic referral center PATIENT SAMPLE: Adult patients undergoing lumbar spine surgery from March 2017 to January 2021 who sustained an incidental durotomy. Patients undergoing surgery for infection were excluded.

Outcome Measures: The primary outcome was failure of the repair as determined by a return to the operating room for re-exploration of a persistent cerebrospinal fluid (CSF) leak within 30 days of the index procedure. A secondary outcome was the incidence of a postoperative positional headache, and if present, the method used to obtain resolution. The primary predictor was use of a suture and hydrogel technique ("hydrogel" group), or the use of an epidural blood patch ("EBP" group).

Methods: The method for applying an open epidural blood patch is presented in detail and involves primarily repairing the durotomy followed by allowing whole blood to pool and clot in the operative field until the durotomy is completely covered. This was compared with a group of patients undergoing secondary augmentation with commercially available hydrogel. In both groups, mechanical resistance to CSF leakage was confirmed with direct visualization and a Valsalva maneuver, respectively. Patients were instructed to remain flat until the morning after surgery. Chart review was used for data abstraction on preoperative, demographic, perioperative, and postoperative clinical factors. To compare between the hydrogel and EBP group, Wilcoxon rank-sum testing was used to test for non-parametric comparisons of means, and chi-square testing between binomial data.

Results: Of 732 patients during the study period, forty-eight patients met study criteria. Twenty-five patients were in the hydrogel group and 23 in the EBP group. Mean age was 69.3 years (standard error 1.3 years). Patients were predominantly female (n = 31, 64.6%) with a mean BMI of 29.5 (SE 0.8), with no significant baseline differences between the hydrogel and EBP groups. Two patients in the hydrogel group (8.0%) and two in the EBP group (8.7%) had mild positional headaches postoperatively that resolved without intervention within 24 hours. One (4.3%) patient in the EBP group had positional headaches following an initial headache-free period; this patient was returned to the operating room and no evidence of a persistent CSF leak was found despite meticulous exploration.

Conclusions: An open, intraoperatively placed epidural blood patch may be an efficacious and cost-effective way to manage an incidental durotomy. This method merits further study as an allergy-free, no swell, cost-neutral method of dural repair augmentation.
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http://dx.doi.org/10.1016/j.spinee.2021.06.011DOI Listing
June 2021

Compositional Differences in the Oral Microbiome of E-cigarette Users.

Front Microbiol 2021 31;12:599664. Epub 2021 May 31.

Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, United States.

Electronic (e)-cigarettes have been advocated as a safer alternative to conventional tobacco cigarettes. However, there is a paucity of data regarding the impact of e-cigarette aerosol deposition on the human oral microbiome, a key component in human health and disease. We aimed to fill this knowledge gap through a comparative analysis of the microbial community profiles from e-cigarette users and healthy controls [non-smokers/non-vapers (NSNV)]. Moreover, we sought to determine whether e-cigarette aerosol exposure from vaping induces persistent changes in the oral microbiome. To accomplish this, salivary and buccal mucosa samples were collected from e-cigarette users and NSNV controls, with additional oral samples collected from e-cigarette users after 2 weeks of decreased use. Total DNA was extracted from all samples and subjected to PCR amplification and sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene. Our analysis revealed several prominent differences associated with vaping, specific to the sample type (i.e., saliva and buccal). In the saliva, e-cigarette users had a significantly higher alpha diversity, observed operational taxonomic units (OTUs) and Faith's phylogenetic diversity (PD) compared to NSNV controls, which declined with decreased vaping. The buccal mucosa swab samples were marked by a significant shift in beta diversity between e-cigarette users and NSNV controls. There were also significant differences in the relative abundance of several bacterial taxa, with a significant increase in and in e-cigarette users. In addition, nasal swabs demonstrated a trend toward higher colonization rates with in e-cigarette users relative to controls (19 vs. 7.1%; = n.s.). Overall, these data reveal several notable differences in the oral bacterial community composition and diversity in e-cigarette users as compared to NSNV controls.
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http://dx.doi.org/10.3389/fmicb.2021.599664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200533PMC
May 2021

Novel Applications of Spinal Navigation in Deformity and Oncology Surgery-Beyond Screw Placement.

Oper Neurosurg (Hagerstown) 2021 06;21(Supp 1):S23-S38

Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Computer-assisted navigation has made a major impact on spine surgery, providing surgeons with technological tools to safely place instrumentation anywhere in the spinal column. With advances in intraoperative image acquisition, registration, and processing, many surgeons are now using navigation in their practices. The incorporation of navigation into the workflow of surgeons continues to expand with the evolution of minimally invasive techniques and robotic surgery. While numerous investigators have demonstrated the benefit of navigation for improving the accuracy of instrumentation, few have reported applying this technology to other aspects of spine surgery. Surgeries to correct spinal deformities and resect spinal tumors are technically demanding, incorporating a wide range of techniques not only for instrumentation placement but also for osteotomy planning and executing the goals of surgery. Although these subspecialties vary in their objectives, they share similar challenges with potentially high complications, invasiveness, and consequences of failed execution. Herein, we highlight the utility of using spinal navigation for applications beyond screw placement: specifically, for planning and executing osteotomies and guiding the extent of tumor resection. A narrative review of the work that has been done is supplemented with illustrative cases demonstrating these applications.
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http://dx.doi.org/10.1093/ons/opaa322DOI Listing
June 2021

Racial Disparities in Perioperative Morbidity Following Oncological Spine Surgery.

Global Spine J 2021 Jun 14:21925682211022290. Epub 2021 Jun 14.

Spine Research Group, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA.

Study Design: Retrospective cohort study.

Objective: To assess the impact of race on complications following spinal tumor surgery.

Methods: Adults with cancer who underwent spine tumor surgery were identified in the American College of Surgeons National Surgical Quality Improvement Program datasets from 2012 to 2016. Clavien-Dindo Grade I-II (minor complications) and Clavien-Dindo Grade III-V (major complications including 30-day mortality) complications were compared between non-Hispanic Whites (NHW) and Black patients. A multivariable analysis was also conducted.

Results: Of 1,226 identified patients, 85.9% were NHW (n = 1,053) and 14.1% were Black (n = 173). The overall rate of Grade I-II complications was 16.2%; 15.1% for NHW patients and 23.1% for Black patients ( = .008). On multivariable analysis, Black patients had significantly higher odds of having a minor complication (OR 1.87; 95% CI, 1.16-3.01; = .010). On the other hand, the overall rate of Grade III-V complications was 13.3%; 12.5% for NHW patients and 16.2% for Black patients ( = .187). On multivariable analysis, Black race was not independently associated with major complications (OR 1.26; 95% CI, 0.71-2.23; = .430). Median length of stay was 8 days (IQR 5-13) for NHW patients and 10 days (IQR 6-15) for Black patients ( = .011).

Conclusion: Black patients who underwent metastatic spinal tumor surgery were at a significantly increased risk of perioperative morbidity compared to NHW patients independent of baseline and operative characteristics. Major complications did not differ between groups. Race should be further studied in the context of metastatic spine disease to improve our understanding of these disparities.
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http://dx.doi.org/10.1177/21925682211022290DOI Listing
June 2021

Chronic E-Cigarette Aerosol Inhalation Alters the Immune State of the Lungs and Increases ACE2 Expression, Raising Concern for Altered Response and Susceptibility to SARS-CoV-2.

Front Physiol 2021 31;12:649604. Epub 2021 May 31.

Pulmonary Critical Care Section, VA San Diego Healthcare System, La Jolla, CA, United States.

Conventional smoking is known to both increase susceptibility to infection and drive inflammation within the lungs. Recently, smokers have been found to be at higher risk of developing severe forms of coronavirus disease 2019 (COVID-19). E-cigarette aerosol inhalation (vaping) has been associated with several inflammatory lung disorders, including the recent e-cigarette or vaping product use-associated lung injury (EVALI) epidemic, and recent studies have suggested that vaping alters host susceptibility to pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To assess the impact of vaping on lung inflammatory pathways, including the angiotensin-converting enzyme 2 (ACE2) receptor known to be involved in SARS-CoV-2 infection, mice were exposed to e-cigarette aerosols for 60 min daily for 1-6 months and underwent gene expression analysis. Hierarchical clustering revealed extensive gene expression changes occurred in the lungs of both inbred C57BL/6 mice and outbred CD1 mice, with 2,933 gene expression changes in C57BL/6 mice, and 2,818 gene expression changes in CD1 mice (>abs 1.25-fold change). Particularly, large reductions in IgA and CD4 were identified, indicating impairment of host responses to pathogens reductions in immunoglobulins and CD4 T cells. CD177, facmr, tlr9, fcgr1, and ccr2 were also reduced, consistent with diminished host defenses decreased neutrophils and/or monocytes in the lungs. Gene set enrichment (GSE) plots demonstrated upregulation of gene expression related to cell activation specifically in neutrophils. As neutrophils are a potential driver of acute lung injury in COVID-19, increased neutrophil activation in the lungs suggests that vapers are at higher risk of developing more severe forms of COVID-19. The receptor through which SARS-CoV-2 infects host cells, ACE2, was found to have moderate upregulation in mice exposed to unflavored vape pens, and further upregulation (six-fold) with JUUL mint aerosol exposure. No changes were found in mice exposed to unflavored Mod device-generated aerosols. These findings suggest that specific vaping devices and components of e-liquids have an effect on ACE2 expression, thus potentially increasing susceptibility to SARS-CoV-2. In addition, exposure to e-cigarette aerosols both with and without nicotine led to alterations in eicosanoid lipid profiles within the BAL. These data demonstrate that chronic, daily inhalation of e-cigarette aerosols fundamentally alters the inflammatory and immune state of the lungs. Thus, e-cigarette vapers may be at higher risk of developing infections and inflammatory disorders of the lungs.
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http://dx.doi.org/10.3389/fphys.2021.649604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194307PMC
May 2021

Characterizing Health-Related Quality of Life by Ambulatory Status in Patients With Spinal Metastases.

Spine (Phila Pa 1976) 2021 Jun 8. Epub 2021 Jun 8.

Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 Department of Orthopaedic Surgery, NYU Langone Medical Center, New York University, Westbury, NY 11590.

Study Design: Retrospective review of prospective longitudinal data.

Objective: To determine health-related quality of life (HRQL) utilities associated with specific ambulatory states in patients with spinal metastases: independent, ambulatory with assistance and non-ambulatory.

Summary Of Background Data: It is assumed that HRQL is aligned with ambulatory ability in patients with spinal metastases. Few studies have effectively considered these parameters while also accounting for clinical confounders.

Methods: We used prospective longitudinal data from patients treated at one of three tertiary medical centers (2017-2019). HRQL was characterized using the Euroquol-5-dimension (EQ5D) inventory. We performed standardized estimations of HRQL stratified by ambulatory state using generalized linear modeling that accounted for patient age at presentation, biologic sex, follow-up duration, operative or non-operative management and repeated measures within the same participant.

Results: We evaluated 675 completed EQ5D assessments, with 430 for independent ambulators, 205 for ambulators with assistance and 40 for non-ambulators. The average age of the cohort was 61.5. The most common primary cancer was lung (20%), followed by breast (18%). Forty-one percent of assessments were performed for participants treated surgically. Mortality occurred in 51% of the cohort. The standardized EQ5D utility for patients with spinal metastases and independent ambulatory function was 0.76 (95% CI 0.74, 0.78). Among those ambulatory with assistance, the standardized EQ5D utility was 0.59 (95% CI 0.57, 0.61). For non-ambulators, the standardized EQ5D utility was 0.14 (95% CI 0.09, 0.19).

Conclusions: Patients with spinal metastases and independent ambulatory function have a HRQL similar to patients with primary cancers and no spinal involvement. Loss of ambulatory ability leads to a 22% decrease in HRQL for ambulation with assistance and an 82% reduction among non-ambulators. Given prior studies demonstrate superior maintenance of ambulatory function with surgery for spinal metastases, our results support surgical consideration to the extent that it is clinically warranted.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000004139DOI Listing
June 2021

Association of Spinal Alignment Correction With Patient-Reported Outcomes in Adult Cervical Deformity: Review of the Literature.

Neurospine 2021 05 18. Epub 2021 May 18.

Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Objective: Adult cervical deformity (ACD) is a debilitating spinal condition that causes significant pain, neurologic dysfunction, and functional impairment. Surgery is often performed to correct cervical alignment, but the optimal amount of correction required to improve patient-reported outcomes (PROs) are not yet well-defined.

Methods: A review of the literature was performed and Fisher's z-transformation (Zr) was used to pool the correlation coefficients between alignment parameters and PROs. The strength of correlation was defined according to the following: poor (0 < r ≤ 0.3), fair (0.3 < r ≤ 0.5), moderate (0.5 < r ≤ 0.8), and strong (0.8 < r ≤ 1).

Results: Increased C2-C7 SVA was fairly associated with increased Neck Disability Index (NDI) (pooled Zr = 0.31; 95% CI, -0.03, 0.58). Changes in TS-CL poorly correlated with NDI (pooled Zr = -0.04; 95% CI, -0.23-0.30). Increased C7-S1 was poorly associated with worse EQ-5D (pooled Zr = -0.22; 95% CI, -0.36, -0.06). Correction of horizontal gaze (CBVA) did not correlate with legacy metrics. mJOA correlated with C2-slope, C7-S1, and C2-S1.

Conclusion: Spinal alignment parameters variably correlated with improved HRQoL and myelopathy after corrective surgery for ACD. Further studies evaluating legacy PROs, PROMIS, and ACD specific instruments are needed for further validation.
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http://dx.doi.org/10.14245/ns.2040656.328DOI Listing
May 2021

Modified-frailty index does not independently predict complications, hospital length of stay or 30-day readmission rates following posterior lumbar decompression and fusion for spondylolisthesis.

Spine J 2021 May 16. Epub 2021 May 16.

Department of Neurosurgery, John Hopkins School of Medicine, Baltimore, MD.

Background Context: Frailty has been associated with inferior surgical outcomes in various fields of spinal surgery. With increasing healthcare costs, hospital length of stay (LOS) and unplanned readmissions have emerged as clinical proxies reflecting overall value of care. However, there is a paucity of data assessing the impact that baseline frailty has on quality of care in patients with spondylolisthesis.

Purpose: The aim of this study was to investigate the impact that frailty has on LOS, complication rate, and unplanned readmission after posterior lumbar spinal fusion for spondylolisthesis.

Study Design: A retrospective cohort study was performed using the National Surgical Quality Improvement Program (NSQIP) database from 2010 through 2016.

Patient Sample: All adult (≥18 years old) patients who underwent lumbar spinal decompression and fusion for spondylolisthesis were identified using ICD-9-CM diagnosis and procedural coding systems. We calculated the modified frailty index (mFI) for each patient using 5 dichotomous comorbidities - diabetes mellitus, congestive heart failure, hypertension requiring medication, chronic obstructive pulmonary disease, and dependent functional status. Each comorbidity is assigned 1 point and the points are summed to give a score between 0 and 5. As in previous literature, we defined a score of 0 as "not frail", 1 as "mild" frailty, and 2 or greater as "moderate to severe" frailty.

Outcome Measures: Patient demographics, comorbidities, complications, LOS, readmission, and reoperation were assessed.

Methods: A multivariate logistic regression analysis was used to identify independent predictors of adverse events (AEs), extended LOS, complications, and unplanned readmission.

Results: There were a total of 5,296 patients identified, of which 2,030 (38.3%) were mFI=0, 2,319 (43.8%) patients mFI=1, and 947 (17.9%) were mFI ≥2. The mFI≥2 cohort was older (p≤.001) and had a greater average BMI (p≤.001). The mFI≥2 cohort had a slightly longer hospital stay (3.7 ± 2.3 days vs. mFI=1: 3.5 ± 2.8 days and mFI=0: 3.2 ± 2.1 days,p≤.001). Both surgical AEs and medical AEs were significantly greater in the mFI≥2 cohort than the other cohorts, (2.6% vs. mFI=1: 1.8% and mFI=0: 1.2%,p=.022) and (6.3% vs. mFI=1: 4.8% and mFI=0: 2.6%,p≤.001), respectively. While there was no significant difference in reoperation rates, the mFI≥2 cohort had greater unplanned 30-day readmission rates (8;4% vs. mFI=5.6: 4.8% and mFI=0: 3.4%,p≤.001). However, on multivariate regression analysis, mFI≥2 was not a significant independent predictor of LOS (p=.285), complications (p=.667), or 30-day unplanned readmission (p=.378).

Conclusions: Our study indicates that frailty, as measured by the mFI, does not significantly predict LOS, 30-day adverse events, or 30-day unplanned readmission in patients undergoing lumbar spinal decompression and fusion for spondylolisthesis. Further work is needed to better define variable inputs that make up frailty to optimize surgical outcome prediction tools that impact the value of care.
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http://dx.doi.org/10.1016/j.spinee.2021.05.011DOI Listing
May 2021

Increased peripheral blood neutrophil activation phenotypes and NETosis in critically ill COVID-19 patients: a case series and review of the literature.

Clin Infect Dis 2021 May 14. Epub 2021 May 14.

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego (UCSD), La Jolla, CA 92093, USA.

Background: Increased inflammation has been well defined in COVID-19, while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets.

Methods: Blood was obtained serially from critically ill COVID-19 patients for eleven days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis and cytokine levels were assessed. Lung tissue was obtained immediately post-mortem for immunostaining. Pubmed searches for neutrophils, lung and COVID-19 yielded ten peer-reviewed research articles in English.

Results: Elevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified both at first measurement and across hospitalization (p<0.0001). COVID neutrophils had exaggerated oxidative burst (p<0.0001), NETosis (p<0.0001) and phagocytosis (p<0.0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of SARS-CoV-2 infected lungs available for examination (2 out of 5). While elevations in IL-8 and ANC correlated with disease severity, plasma IL-8 levels alone correlated with death.

Conclusions: Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data shows that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.
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http://dx.doi.org/10.1093/cid/ciab437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241438PMC
May 2021

Microsurgical resection of foramen magnum meningioma: multi-institutional retrospective case series and proposed surgical risk scoring system.

J Neurooncol 2021 Jun 10;153(2):331-342. Epub 2021 May 10.

Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, 94305, USA.

Purpose: Foramen magnum meningiomas (FMMs) are a major surgical challenge, due to relevant surgical morbidity and mortality. The paper aims to review the clinical (symptomatic improvement, complication rate, length of hospital stay) and radiological outcome (completeness of resection) of microsurgical resection of FMMs, and to identify predictors of complications.

Methods: A multi-institutional retrospective review of prospectively maintained database of FMMs included 51 patients (74.5% females) with a median tumor volume of 8.18 cm (range, 1.77-57.9 cm) and median follow-up of 36 months (range, 0.30-180.0 months). Tumors were resected though suboccipital approach (58.8%) or posterior-lateral approaches (39.3%), including far-lateral, extreme lateral and transcondylar approaches.

Results: Gross-total resection (GTR) was achieved in 80.4% and 98% of cases did not present tumor regrowth or recurrence. Clinical symptoms improved in 34 patients (66.7%) and worsened in 5 (9.8%). The median length of hospital stay was 5 days. Mortality was null. Postoperative complications developed in 15 patients (29.4%), with cerebrospinal fluid leak (7.8%) and lower cranial nerves deficits (7.8%) as the most frequent. Craniospinal location (p = 0.03), location anterior to the dentate ligament (DL) (p = 0.02), involvement of vertebral artery (VA) (p = 0.03) were significantly associated with complication rate. These three elements allow calculating the Foramen Magnum Meningioma Risk Score (FRMMRS), to estimate the risk of post-operative complications.

Conclusion: Microsurgical resection allows for high GTR rate and low rate of tumor regrowth or recurrence, despite complications in one third of the patients. The FMMRS allows classifying FMMs and estimating the risk of post-operative complications.
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http://dx.doi.org/10.1007/s11060-021-03773-zDOI Listing
June 2021

Real-world performance of the MiniMed™ 670G system in Europe.

Diabetes Obes Metab 2021 Aug 27;23(8):1942-1949. Epub 2021 May 27.

Medtronic International Trading Sàrl, Tolochenaz, Switzerland.

Aim: To evaluate the real-world performance of the MiniMed 670G system in Europe, in individuals with diabetes.

Materials And Methods: Data uploaded from October 2018 to July 2020 by individuals living in Europe were aggregated and retrospectively analysed. The mean glucose management indicator (GMI), percentage of time spent within (TIR), below (TBR) and above (TAR) glycaemic ranges, system use and insulin consumed in users with 10 or more days of sensor glucose data after initial Auto Mode start were determined. Another analysis based on suboptimally (GMI > 8.0%) and well-controlled (GMI < 7.0%) glycaemia pre-Auto Mode initiation was also performed.

Results: Users (N = 14 899) spent a mean of 81.4% of the time in Auto Mode and achieved a mean GMI of 7.0% ± 0.4%, TIR of 72.0% ± 9.7%, TBR less than 3.9 mmol/L of 2.4% ± 2.1% and TAR more than 10 mmol/L of 25.7% ± 10%, after initiating Auto Mode. When compared with pre-Auto Mode initiation, GMI was reduced by 0.3% ± 0.4% and TIR increased by 9.6% ± 9.9% (P < .0001 for both). Significantly improved glycaemic control was observed irrespective of pre-Auto Mode GMI levels of less than 7.0% or of more than 8.0%. While the total daily dose of insulin increased for both groups, a greater increase was observed in the latter, an increase primarily due to increased basal insulin delivery. By contrast, basal insulin decreased slightly in well-controlled users.

Conclusions: Most MiniMed 670G system users in Europe achieved TIR more than 70% and GMI less than 7% while minimizing hypoglycaemia, in a real-world environment. These international consensus-met outcomes were enabled by automated insulin delivery meeting real-time insulin requirements adapted to each individual user.
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http://dx.doi.org/10.1111/dom.14424DOI Listing
August 2021

Race Is an Independent Predictor for Nonroutine Discharges After Spine Surgery for Spinal Intradural/Cord Tumors.

World Neurosurg 2021 Jul 30;151:e707-e717. Epub 2021 Apr 30.

Department of Neurosurgery, John Hopkins School of Medicine, Baltimore, Maryland, USA.

Objective: The aim of this study was to determine if race was an independent predictor of extended length of stay (LOS), nonroutine discharge, and increased health care costs after surgery for spinal intradural/cord tumors.

Methods: A retrospective cohort study was performed using the National Inpatient Sample database from 2016 to 2017. All adult (>18 years old) inpatients who underwent surgical intervention for a benign or malignant spinal intradural/cord tumor were identified using International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis and procedural coding systems. Patients were then categorized based on race: White, African American (AA), Hispanic, and other. Postoperative complications, LOS, discharge disposition, and total cost of hospitalization were assessed. A backward stepwise multivariable logistic regression analysis was used to identify independent predictors of extended LOS and nonroutine discharge disposition.

Results: Of 3595 patients identified, there were 2620 (72.9%) whites (W), 310 (8.6%) AAs/blacks, 275 (7.6%) Hispanic (H), and 390 (10.8%) other (O). Postoperative complication rates were similar among the cohorts (P = 0.887). AAs had longer mean (W, 5.4 ± 4.2 days vs. AA, 8.9 ± 9.5 days vs. H, 5.9 ± 3.9 days vs. O, 6.1 ± 3.9 days; P = 0.014) length of hospitalizations than the other cohorts. The overall incidence of nonroutine discharge was 55% (n = 1979), with AA race having the highest rate of nonroutine discharges (W, 53.8% vs. AA, 74.2% vs. H, 45.5% vs. O, 43.6%; P = 0.016). On multivariate regression analysis, AA race was the only significant racial independent predictor of nonroutine discharge disposition (odds ratio, 3.32; confidence interval, 1.67-6.60; P < 0.001), but not extended LOS (P = 0.209).

Conclusions: Our study indicates that AA race is an independent predictor of nonroutine discharge disposition in patients undergoing surgical intervention for a spinal intradural/cord tumor.
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http://dx.doi.org/10.1016/j.wneu.2021.04.085DOI Listing
July 2021

Introduction. Treatment of spinal cord and spinal axial tumors.

Neurosurg Focus 2021 05;50(5):E1

5Department of Oncology, Queen's University, Kingston, Ontario, Canada.

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http://dx.doi.org/10.3171/2021.2.FOCUS21113DOI Listing
May 2021

Performance assessment of the metastatic spinal tumor frailty index using machine learning algorithms: limitations and future directions.

Neurosurg Focus 2021 05;50(5):E5

Departments of1Neurosurgery and.

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.
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http://dx.doi.org/10.3171/2021.2.FOCUS201113DOI Listing
May 2021

Interhospital transfer status for spinal metastasis patients in the United States is associated with more severe clinical presentations and higher rates of inpatient complications.

Neurosurg Focus 2021 05;50(5):E4

Departments of1Neurosurgery and.

Objective: In patients with metastatic spinal disease (MSD), interhospital transfer can potentially impact clinical outcomes as the possible benefits of transferring a patient to a higher level of care must be weighed against the negative effects associated with potential delays in treatment. While the association of clinical outcomes and transfer status has been examined in other specialties, the relationship between transfer status, complications, and risk of mortality in patients with MSD has yet to be explored. The purpose of this study was to examine the impact of transfer status on in-hospital mortality and clinical outcomes in patients diagnosed with MSD.

Methods: The National (Nationwide) Inpatient Sample (NIS) database was retrospectively queried for adult patients diagnosed with vertebral pathological fracture and/or spinal cord compression in the setting of metastatic disease between 2012 and 2014. Demographics, baseline characteristics (e.g., metastatic spinal cord compression [MSCC] and paralysis), comorbidities, type of intervention, and relevant patient outcomes were controlled in a multivariable logistic regression model to analyze the association of transfer status with patient outcomes.

Results: Within the 10,360 patients meeting the inclusion and exclusion criteria, higher rates of MSCC (50.2% vs 35.9%, p < 0.001) and paralysis (17.3% vs 8.4%, p < 0.001) were observed in patients transferred between hospitals compared to those directly admitted. In univariable analysis, a higher percentage of transferred patients underwent surgical intervention (p < 0.001) when compared with directly admitted patients. After controlling for significant covariates and surgical intervention, transferred patients were more likely to develop in-hospital complications (OR 1.34, 95% CI 1.18-1.52, p < 0.001), experience prolonged length of stay (OR 1.33, 95% CI 1.16-1.52, p < 0.001), and have a discharge disposition other than home (OR 1.70, 95% CI 1.46-1.98, p < 0.001), with no significant difference in inpatient mortality rates.

Conclusions: Patients with MSD who were transferred between hospitals demonstrated more severe clinical presentations and higher rates of inpatient complications compared to directly admitted patients, despite demonstrating no difference in in-hospital mortality rates.
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http://dx.doi.org/10.3171/2021.2.FOCUS201085DOI Listing
May 2021

Systematic review of charged-particle therapy for chordomas and sarcomas of the mobile spine and sacrum.

Neurosurg Focus 2021 05;50(5):E17

1Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Objective: Long-term local control in patients with primary chordoma and sarcoma of the spine and sacrum is increasingly reliant upon en bloc resection with negative margins. At many institutions, adjuvant radiation is recommended; definitive radiation is also recommended for the treatment of unresectable tumors. Because of the high off-target radiation toxicities associated with conventional radiotherapy, there has been growing interest in the use of proton and heavy-ion therapies. The aim of this study was to systematically review the literature regarding these therapies.

Methods: The PubMed, OVID, Embase, and Web of Science databases were queried for articles describing the use of proton, combined proton/photon, or heavy-ion therapies for adjuvant or definitive radiotherapy in patients with primary sarcoma or chordoma of the mobile spine and sacrum. A qualitative synthesis of the results was performed, focusing on overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and disease-specific survival (DSS); local control; and postradiation toxicities.

Results: Of 595 unique articles, 64 underwent full-text screening and 38 were included in the final synthesis. All studies were level III or IV evidence with a high risk of bias; there was also significant overlap in the reported populations, with six centers accounting for roughly three-fourths of all reports. Five-year therapy outcomes were as follows: proton-only therapies, OS 67%-82%, PFS 31%-57%, and DFS 52%-62%; metastases occurred in 17%-18% and acute toxicities in 3%-100% of cases; combined proton/photon therapy, local control 62%-85%, OS 78%-87%, PFS 90%, and DFS 61%-72%; metastases occurred in 12%-14% and acute toxicities in 84%-100% of cases; and carbon ion therapy, local control 53%-100%, OS 52%-86%, PFS (only reported for 3 years) 48%-76%, and DFS 50%-53%; metastases occurred in 2%-39% and acute toxicities in 26%-48%. There were no studies directly comparing outcomes between photon and charged-particle therapies or comparing outcomes between radiation and surgical groups.

Conclusions: The current evidence for charged-particle therapies in the management of sarcomas of the spine and sacrum is limited. Preliminary evidence suggests that with these therapies local control and OS at 5 years are comparable among various charged-particle options and may be similar between those treated with definitive charged-particle therapy and historical surgical cohorts. Further research directly comparing charged-particle and photon-based therapies is necessary.
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http://dx.doi.org/10.3171/2021.2.FOCUS201059DOI Listing
May 2021

Feasibility of achieving planned surgical margins in primary spine tumor: a PTRON study.

Neurosurg Focus 2021 05;50(5):E16

1Combined Neurosurgical and Orthopaedic Spine Program, University of British Columbia, Vancouver, British Columbia, Canada.

Objective: Oncological resection of primary spine tumors is associated with lower recurrence rates. However, even in the most experienced hands, the execution of a meticulously drafted plan sometimes fails. The objectives of this study were to determine how successful surgical teams are at achieving planned surgical margins and how successful surgeons are in intraoperatively assessing tumor margins. The secondary objective was to identify factors associated with successful execution of planned resection.

Methods: The Primary Tumor Research and Outcomes Network (PTRON) is a multicenter international prospective registry for the management of primary tumors of the spine. Using this registry, the authors compared 1) the planned surgical margin and 2) the intraoperative assessment of the margin by the surgeon with the postoperative assessment of the margin by the pathologist. Univariate analysis was used to assess whether factors such as histology, size, location, previous radiotherapy, and revision surgery were associated with successful execution of the planned margins.

Results: Three hundred patients were included. The surgical plan was successfully achieved in 224 (74.7%) patients. The surgeon correctly assessed the intraoperative margins, as reported in the final assessment by the pathologist, in 239 (79.7%) patients. On univariate analysis, no factor had a statistically significant influence on successful achievement of planned margins.

Conclusions: In high-volume cancer centers around the world, planned surgical margins can be achieved in approximately 75% of cases. The morbidity of the proposed intervention must be balanced with the expected success rate in order to optimize patient management and surgical decision-making.
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http://dx.doi.org/10.3171/2021.2.FOCUS201091DOI Listing
May 2021

Safety and efficacy of cement augmentation with fenestrated pedicle screws for tumor-related spinal instability.

Neurosurg Focus 2021 05;50(5):E12

Objective: Achieving rigid spinal fixation can be challenging in patients with cancer-related instability, as factors such as osteopenia, radiation, and immunosuppression adversely affect bone quality. Augmenting pedicle screws with cement is a strategy to overcome construct failure. This study aimed to assess the safety and efficacy of cement augmentation with fenestrated pedicle screws in patients undergoing posterior, open thoracolumbar surgery for spinal metastases.

Methods: A retrospective review was performed for patients who underwent surgery for cancer-related spine instability from 2016 to 2019 at the Massachusetts General Hospital. Patient demographics, surgical details, radiographic characteristics, patterns of cement extravasation, complications, and prospectively collected Patient-Reported Outcomes Measurement Information System Pain Interference and Pain Intensity scores were analyzed using descriptive statistics. Logistic regression was performed to determine factors associated with cement extravasation.

Results: Sixty-nine patients underwent open posterior surgery with a total of 502 cement-augmented screws (mean 7.8 screws per construct). The median follow-up period for those who survived past 90 days was 25.3 months (IQR 10.8-34.6 months). Thirteen patients (18.8%) either died within 90 days or were lost to follow-up. Postoperative CT was performed to assess the instrumentation and patterns of cement extravasation. There was no screw loosening, pullout, or failure. The rate of cement extravasation was 28.9% (145/502), most commonly through the segmental veins (77/145, 53.1%). Screws breaching the lateral border of the pedicle but with fenestrations within the vertebral body were associated with a higher risk of leakage through the segmental veins compared with screws without any breach (OR 8.77, 95% CI 2.84-29.79; p < 0.001). Cement extravasation did not cause symptoms except in 1 patient who developed a symptomatic thoracic radiculopathy requiring decompression. There was 1 case of asymptomatic pulmonary cement embolism. Patients experienced significant pain improvement at the 3-month follow-up, with decreases in Pain Interference (mean change 15.8, 95% CI 14.5-17.1; p < 0.001) and Pain Intensity (mean change 28.5, 95% CI 26.7-30.4; p < 0.001).

Conclusions: Cement augmentation through fenestrated pedicle screws is a safe and effective option for spine stabilization in the cancer population. The risk of clinically significant adverse events from cement extravasation is very low.
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http://dx.doi.org/10.3171/2021.2.FOCUS201121DOI Listing
May 2021

Spnal metastases 2021: a review of the current state of the art and future directions.

Spine J 2021 Apr 19. Epub 2021 Apr 19.

Department of Orthopaedic Surgery, Brigham and Women's Hospital, Harvard medical School, Boston, MD 02115, USA.

Spinal metastases are an increasing societal health burden secondary to improvements in systemic therapy. Estimates indicate that 100,000 or more people have symptomatic spine metastases requiring management. While open surgery and external beam radiotherapy have been the pillars of treatment, there is growing interest in more minimally invasive technologies (eg separation surgery) and non-operative interventions (eg percutaneous cementoplasty, stereotactic radiosurgery). The great expansion of these alternatives to open surgery and the prevalence of adjuvant therapeutic options means that treatment decision making is now complex and reliant upon multidisciplinary collaboration. To help facilitate construction of care plans that meet patient goals and expectations, clinical decision aids and prognostic scores have been developed. These have been shown to have superior predictive value relative to more classic prediction models and may become an increasingly important aspect of the clinical practice of spinal oncology. Here we overview current therapeutic advances in the management of spine metastases and highlight emerging areas for research. Given the rapid advancements in surgical technologies and adjuvants, the field is likely to undergo further transformative changes in the coming decade.
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http://dx.doi.org/10.1016/j.spinee.2021.04.012DOI Listing
April 2021

Cost and Health Care Resource Utilization Differences After Spine Surgery for Bony Spine versus Primary Intradural Spine Tumors.

World Neurosurg 2021 Jul 15;151:e286-e298. Epub 2021 Apr 15.

Department of Neurosurgery, John Hopkins School of Medicine, Baltimore, Maryland, USA.

Objective: The aim of this study was to compare complication rates, length of stay (LOS), and hospital costs after spine surgery for bony spine tumors and intradural spinal neoplasms.

Methods: A retrospective cohort study was performed using the National Inpatient Sample database from 2016 to 2017. All adult inpatients who underwent surgical intervention for a primary intradural spinal tumor or primary/metastatic bony spine tumor were identified using International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis/procedural coding systems. Patient demographics, comorbidities, intraoperative variables, complications, LOS, discharge disposition, and total cost of hospitalization were assessed. Backward stepwise multivariable logistic regression analyses were used to identify independent predictors of perioperative complication, extended LOS (≥75th percentile), and increased cost (≥75th percentile).

Results: A total of 9855 adult patients were included in the study; 3850 (39.1%) were identified as having a primary intradural spinal tumor and 6005 (60.9%) had a primary or metastatic bony spine tumor. Those treated for bony tumors had more comorbidities (≥3, 67.8% vs. 29.2%) and more commonly experienced ≥1 complications (29.9% vs. 7.9%). Multivariate analyses also showed those in the bony spine cohort had a higher odds of experiencing ≥1 complications (odds ratio [OR], 4.26; 95% confidence interval [CI], 3.04-5.97; P < 0.001), extended LOS (OR, 2.44; 95% CI, 1.75-3.38; P < 0.001), and increased cost (OR, 5.32; 95% CI, 3.67-7.71; P < 0.001).

Conclusions: Relative to patients being treated for primary intradural tumors, those undergoing spine surgery for bony spine tumors experience significantly higher risk for perioperative complications, extended LOS, and increased cost of hospital admission. Further identification of patient and treatment characteristics that may optimize management of spine oncology may reduce adverse outcomes, improve patient care, and reduce health care resources.
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http://dx.doi.org/10.1016/j.wneu.2021.04.015DOI Listing
July 2021

Risk Factors for 30-Day Unplanned Readmission After Hepatectomy: Analysis of 438 Pediatric Patients from the ACS-NSQIP-P Database.

J Gastrointest Surg 2021 Apr 6. Epub 2021 Apr 6.

Department of Pediatrics, Vagelos College of Physician and Surgeons, Columbia University, New York, NY, USA.

Background: Hepatic resections are uncommon in children. Most studies reporting complications of these procedures and risk factors associated with unplanned readmissions are limited to retrospective data from single centers. We investigated risk factors for 30-day unplanned readmission after hepatectomy in children using the American College of Surgeons National Surgical Quality Improvement-Pediatric database.

Methods: The database was queried for patients aged 0-18 years who underwent hepatectomy for the treatment of liver lesions from 2012 to 2018. Chi-squared tests were performed to evaluate for potential risk factors for unplanned readmissions. A multivariate regression analysis was performed to identify independent predictors for unplanned 30-day readmissions.

Results: Among 438 children undergoing hepatectomy, 64 (14.6%) had unplanned readmissions. The median age of the hepatectomy cohort was 1 year (0-17); 55.5% were male. Patients readmitted had significantly higher rates of esophageal/gastric/intestinal disease (26.56% vs. 14.97%; p=0.022), current cancer (85.94% vs. 75.67%; p=0.012), and enteral and parenteral nutritional support (31.25% vs. 17.65%; p=0.011). Readmitted patients had significantly higher rates of perioperative blood transfusion (67.19% vs. 52.41%; p=0.028), organ/space surgical site infection (10.94% vs. 1.07%; p<.001), sepsis (15.63% vs. 3.74%; p<.001), and total parenteral nutrition at discharge (9.09% vs. 2.66%; p=0.041). Organ/space surgical site infection was an independent risk factor for unplanned readmission (OR=9.598, CI [2.070-44.513], p=0.004) by multivariable analysis.

Conclusion: Unplanned readmissions after liver resection are frequent in pediatric patients. Organ/space surgical site infections may identify patients at increased risk for unplanned readmission. Strategies to reduce these complications may decrease morbidity and costs associated with unplanned readmissions.
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http://dx.doi.org/10.1007/s11605-021-04995-2DOI Listing
April 2021

Prospective comparison of the accuracy of the New England Spinal Metastasis Score (NESMS) to legacy scoring systems in prognosticating outcomes following treatment of spinal metastases.

Spine J 2021 Mar 16. Epub 2021 Mar 16.

Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.

Background Context: We developed the New England Spinal Metastasis Score (NESMS) as a simple, informative, scoring scheme that could be applied to both operative and non-operative patients. The performance of the NESMS to other legacy scoring systems has not previously been compared using appropriately powered, prospectively collected, longitudinal data.

Purpose: To compare the predictive capacity of the NESMS to the Tokuhashi, Tomita and Spinal Instability Neoplastic Score (SINS) in a prospective cohort, where all scores were assigned at the time of baseline enrollment.

Patient Sample: We enrolled 202 patients with spinal metastases who met inclusion criteria between 2017-2019.

Outcome Measures: One-year survival (primary); 3-month mortality and ambulatory function at 3- and 6-months were considered secondarily.

Methods: All prognostic scores were assigned based on enrollment data, which was also assigned as time-zero. Patients were followed until death or survival at 365 days after enrollment. Survival was assessed using Kaplan-Meier curves and score performance was determined via logistic regression testing and observed to expected plots. The discriminative capacity (c-statistic) of the scoring measures were compared via the z-score.

Results: When comparing the discriminative capacity of the predictive scores, the NESMS had the highest c-statistic (0.79), followed by the Tomita (0.69), the Tokuhashi (0.67) and the SINS (0.54). The discriminative capacity of the NESMS was significantly greater (p-value range: 0.02 to <0.001) than any of the other predictive tools. The NESMS was also able to inform independent ambulatory function at 3- and 6-months, a function that was only uniformly replicated by the Tokuhashi score.

Conclusions: The results of this prospective validation study indicate that the NESMS was able to differentiate survival to a significantly higher degree than the Tokuhashi, Tomita and SINS. We believe that these findings endorse the utilization of the NESMS as a prognostic tool capable of informing care for patients with spinal metastases.
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http://dx.doi.org/10.1016/j.spinee.2021.03.007DOI Listing
March 2021

The Prognostic Role of Magnetic Resonance Imaging Biomarkers in Mild Traumatic Injury.

JAMA Netw Open 2021 03 1;4(3):e211824. Epub 2021 Mar 1.

Department of Radiology, Mayo Clinic, Phoenix, Arizona.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.1824DOI Listing
March 2021

Improved Glycemic Outcomes With Medtronic MiniMed Advanced Hybrid Closed-Loop Delivery: Results From a Randomized Crossover Trial Comparing Automated Insulin Delivery With Predictive Low Glucose Suspend in People With Type 1 Diabetes.

Diabetes Care 2021 Apr 12;44(4):969-975. Epub 2021 Feb 12.

Canterbury District Health Board, Christchurch, New Zealand

Objective: To study the MiniMed Advanced Hybrid Closed-Loop (AHCL) system, which includes an algorithm with individualized basal target set points, automated correction bolus function, and improved Auto Mode stability.

Research Design And Methods: This dual-center, randomized, open-label, two-sequence crossover study in automated-insulin-delivery-naive participants with type 1 diabetes (aged 7-80 years) compared AHCL to sensor-augmented pump therapy with predictive low glucose management (SAP + PLGM). Each study phase was 4 weeks, preceded by a 2- to 4-week run-in and separated by a 2-week washout.

Results: The study was completed by 59 of 60 people (mean age 23.3 ± 14.4 years). Time in target range (TIR) 3.9-10 mmol/L (70-180 mg/dL) favored AHCL over SAP + PLGM (70.4 ± 8.1% vs. 57.9 ± 11.7%) by 12.5 ± 8.5% ( < 0.001), with greater improvement overnight (18.8 ± 12.9%, < 0.001). All age-groups (children [7-13 years], adolescents [14-21 years], and adults [>22 years]) demonstrated improvement, with adolescents showing the largest improvement (14.4 ± 8.4%). Mean sensor glucose (SG) at run-in was 9.3 ± 0.9 mmol/L (167 ± 16.2 mg/dL) and improved with AHCL (8.5 ± 0.7 mmol/L [153 ± 12.6 mg/dL], < 0.001), but deteriorated during PLGM (9.5 ± 1.1 mmol/L [17 ± 19.8 mg/dL], < 0.001). TIR was optimal when the algorithm set point was 5.6 mmol/L (100 mg/dL) compared with 6.7 mmol/L (120 mg/dL), 72.0 ± 7.9% vs. 64.6 ± 6.9%, respectively, with no additional hypoglycemia. Auto Mode was active 96.4 ± 4.0% of the time. The percentage of hypoglycemia at baseline (<3.9 mmol/L [70 mg/dL] and ≤3.0 mmol/L [54 mg/dL]) was 3.1 ± 2.1% and 0.5 ± 0.6%, respectively. During AHCL, the percentage time at <3.9 mmol/L (70 mg/dL) improved to 2.1 ± 1.4% ( = 0.034) and was statistically but not clinically reduced for ≤3.0 mmol/L (54 mg/dL) (0.5 ± 0.5%; = 0.025). There was one episode of mild diabetic ketoacidosis attributed to an infusion set failure in combination with an intercurrent illness, which occurred during the SAP + PLGM arm.

Conclusions: AHCL with automated correction bolus demonstrated significant improvement in glucose control compared with SAP + PLGM. A lower algorithm SG set point during AHCL resulted in greater TIR, with no increase in hypoglycemia.
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http://dx.doi.org/10.2337/dc20-2250DOI Listing
April 2021

Intraoperative Diagnosis of Sodium-Glucose Cotransporter 2 Inhibitor-Associated Euglycemic Diabetic Ketoacidosis: A Case Report.

A A Pract 2021 Jan 14;15(1):e01380. Epub 2021 Jan 14.

From the Department of Anesthesiology and Perioperative Medicine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California.

The use of sodium-glucose cotransporter 2 (SGLT2) inhibitors is increasingly common in type 2 diabetes mellitus (DM) management. Patients taking an SGLT2 inhibitor are at risk for euglycemic diabetic ketoacidosis (EDKA). We report an intraoperative diagnosis of EDKA. The patient was found to have an arterial pH of 7.21 and serum beta-hydroxybutyrate of 88.8 mg/dL (normal: <3.0 mg/dL) with serum glucose <250 mg/dL. Acidosis resolved with insulin and glucose infusions. Perioperative specialists must recognize the potential for EDKA in patients taking SGLT2 inhibitors. Expert opinion suggests preoperative cessation for 2-3 days and intraoperative serum ketone concentration measurement for at-risk patients.
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http://dx.doi.org/10.1213/XAA.0000000000001380DOI Listing
January 2021

Commentary: Use of Navigated Ultrasonic Bone Cutting Tool for En Bloc Resection of Thoracic Chondrosarcoma: Technical Report.

Oper Neurosurg (Hagerstown) 2021 01;20(2):E163-E164

Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1093/ons/opaa366DOI Listing
January 2021

E-cigarette aerosols containing nicotine modulate nicotinic acetylcholine receptors and astroglial glutamate transporters in mesocorticolimbic brain regions of chronically exposed mice.

Chem Biol Interact 2021 Jan 23;333:109308. Epub 2020 Nov 23.

Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Toledo, OH, 43614, USA. Electronic address:

Nicotine exposure increases the release of glutamate in part through stimulatory effects on pre-synaptic nicotinic acetylcholine receptors (nAChRs). To assess the impact of chronic electronic (e)-cigarette use on these drug dependence pathways, we exposed C57BL/6 mice to three types of inhalant exposures for 3 months; 1) e-cigarette aerosol generated from liquids containing nicotine (ECN), 2) e-cigarette aerosol generated from liquids containing vehicle chemicals without nicotine (Veh), and 3) air only (AC). We investigated the effects of daily e-cigarette exposure on protein levels of α7 nAChR and α4/β2 nAChR, gene expression and protein levels of astroglial glutamate transporters, including glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT), in the frontal cortex (FC), striatum (STR) and hippocampus (HIP). We found that chronic inhalation of ECN increased α4/β2 nAChR in all brain regions, and increased α7 nAChR expression in the FC and STR. The total GLT-1 relative mRNA and protein expression were decreased in the STR. Moreover, GLT-1 isoforms (GLT-1a and GLT-1b) were downregulated in the STR in ECN group. However, inhalation of e-cigarette aerosol downregulated xCT expression in STR and HIP compared to AC and Veh groups. ECN group had increased brain-derived neurotrophic factor in the STR compared to control groups. Finally, mass spectrometry detected high concentrations of the nicotine metabolite, cotinine, in the FC and STR in ECN group. This work demonstrates that chronic inhalation of nicotine within e-cigarette aerosols significantly alters the expression of nAChRs and astroglial glutamate transporters in specific mesocorticolimbic brain regions.
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http://dx.doi.org/10.1016/j.cbi.2020.109308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752837PMC
January 2021

Spatial proteomics defines the content of trafficking vesicles captured by golgin tethers.

Nat Commun 2020 11 25;11(1):5987. Epub 2020 Nov 25.

MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.

Intracellular traffic between compartments of the secretory and endocytic pathways is mediated by vesicle-based carriers. The proteomes of carriers destined for many organelles are ill-defined because the vesicular intermediates are transient, low-abundance and difficult to purify. Here, we combine vesicle relocalisation with organelle proteomics and Bayesian analysis to define the content of different endosome-derived vesicles destined for the trans-Golgi network (TGN). The golgin coiled-coil proteins golgin-97 and GCC88, shown previously to capture endosome-derived vesicles at the TGN, were individually relocalised to mitochondria and the content of the subsequently re-routed vesicles was determined by organelle proteomics. Our findings reveal 45 integral and 51 peripheral membrane proteins re-routed by golgin-97, evidence for a distinct class of vesicles shared by golgin-97 and GCC88, and various cargoes specific to individual golgins. These results illustrate a general strategy for analysing intracellular sub-proteomes by combining acute cellular re-wiring with high-resolution spatial proteomics.
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http://dx.doi.org/10.1038/s41467-020-19840-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689464PMC
November 2020
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