bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geriatric Conditions Among Middle-aged and Older Adults on Methadone Maintenance Treatment: A Pilot Study
Authors: Han Benjamin H. , Cotton Brandi Parker , Polydorou Soteri , Sherman Scott E. , Ferris Rosie , Arcila-Mesa Mauricio , Qian Yingzhi , McNeely Jennifer 
Published: January 2021

Objectives:
The number of older adults on methadone maintenance treatment (MMT) for opioid use disorder is increasing, but little is known about the characteristics and healthcare needs of this aging treatment population. This population may experience accelerated aging due to comorbidities and health behaviors. The aim of this study was to compare the prevalence of geriatric conditions among adults age ≥50 on MMT to a nationally representative sample of community-dwelling older adults.

Methods:
We performed a geriatric assessment on 47 adults age ≥50 currently on MMT enrolled in 2 opioid treatment programs, in New York City and in East Providence, Rhode Island. We collected data on self-reported geriatric conditions, healthcare utilization, chronic medical conditions, physical function, and substance use. The results were compared to 470 age, sex, and race/ethnicity-matched adults in the national Health and Retirement Study.

Results:
The mean age of the study sample was 58.8 years and 23.4% were female. The most common chronic diseases were hypertension (59.6%) and arthritis (55.3%) with 66% reporting ≥2 diseases. For geriatric conditions, adults on MMT had a significantly higher prevalence of mobility, hearing, and visual impairments as well as falls, urinary incontinence, chronic pain, and insomnia than the Health and Retirement Study sample.

Conclusions:
Older adults on MMT in 2 large opioid treatment programs have a high prevalence of geriatric conditions. An interdisciplinary, geriatric-based approach to care that focuses on function and addresses geriatric conditions is needed to improve the health of this growing population.
Global research collaboration in a pandemic-challenges and opportunities: the COVID-19 Global Rheumatology Alliance
Authors: Robinson Philip C. , Yazdany Jinoos , Machado Pedro M. 
Published: January 2021

Purpose of review
This review discusses the coronavirus disease-2019 (COVID-19) Global Rheumatology Alliance (GRA), the reason for its formation, the challenges with running the registry, and future opportunities for global collaborative research in rheumatology.

Recent findings
The GRA has been successful in collecting and publishing a large volume of case data on patients with rheumatic disease with COVID-19. In addition, the GRA has published reviews, opinion pieces, and patient-directed summaries of research to further assist in disseminating timely and accurate information about COVID-19 in rheumatic diseases. There have been numerous challenges in the journey but they have been addressed through a collaborative problem-solving approach.

Summary
The initial objectives of the GRA to describe the outcomes in patients with rheumatic disease who developed COVID-19 have been achieved. There has been extensive use of the data in the clinic and also to try and understand the mechanisms of disease and opportunities for drug repurposing. There remain numerous important areas for research which the GRA will continue to pursue as the pandemic evolves.
Dual-energy X-ray Absorptiometry Does Not Represent Bone Structure in Patients with Osteoporosis
Authors: Pumberger Matthias , Palmowski Yannick , Strube Patrick , Schwemmer Christin , Roll Stephanie , Zippelius Timo , Putzier Michael 
Published: January 2021

Study Design
Prospective cross-sectional exploratory study.

Objective
To evaluate the correlation between in vivo lumbar dual-energy x-ray absorptiometry (DXA) and parameters of bone architecture in micro–computed tomography (micro-CT) in patients with osteoporosis.

Summary of Background Data
DXA is the current diagnostic standard for evaluating osteoporosis. However, there are various concerns regarding its validity, especially in the spine. No study has so far investigated whether in vivo DXA correlates with the actual lumbar bone architecture.

Methods
Lumbar DXA scans were compared with micro-CT analysis of vertebral biopsies in patients with osteoporotic vertebral fractures (fracture group) and those without (control group). Preoperatively, all patients underwent a DXA scan (L1-L4). Intraoperative biopsies from nonfractured vertebrae (preferably L3) were analyzed by micro-CT regarding bone quantity and quality. The groups were compared regarding differences in DXA and micro-CT results. In each group, a correlation analysis was performed between DXA and micro-CT.

Results
The study included 66 patients (33 per group). Preoperative DXA results were worse in the fracture group than the control group (areal bone mineral density [aBMD] 0.95 vs. 1.31, T-score −1.97 vs. 0.92, each P < 0.001). Micro-CT analysis confirmed differences regarding quantitative parameters (bone/total volume: 0.09 vs. 0.12, P < 0.001) and qualitative parameters (connectivity index: 15.73 vs. 26.67, P < 0.001; structure model index: 2.66 vs. 2.27, P < 0.001; trabecular number: 2.11 vs. 2.28, P = 0.014) of bone architecture between both groups. The DXA results did not correlate with micro-CT parameters in the fracture group. In the control group, correlations were found for some parameters (bone/total volume vs. aBMD: r = 0.51, P = 0.005; trabecular number vs. aBMD: r = 0.56, P = 0.001).

Conclusion
These data constitute the first comparison of DXA measurements with microstructural analysis of vertebral biopsies in patients with osteoporosis. Our results indicate that lumbar DXA neither qualitatively nor quantitatively represents microstructural bone architecture and is therefore not a reliable tool for the evaluation of bone quality in the spine.

Level of Evidence: 3
Residual Motion and Graft Type Do Not Influence Patient-reported Outcomes Following One- or Two-level Anterior Cervical Discectomy and Fusion
Authors: Couch Brandon K. , Wawrose Richard A. , LeVasseur Clarissa M. , Pitcairn Samuel W. , Shaw Jeremy D. , Donaldson William F. , Lee Joon Y. , Anderst William J. 
Published: January 2021

Study Design.
Prospective cohort.

Objective.
The aim of this study was to determine the effect of graft type on residual motion and the relationship among residual motion, smoking, and patient-reported outcome (PRO) scores following anterior cervical discectomy and fusion (ACDF).

Summary of Background Data.
Although most patients develop solid fusion based on static imaging following ACDF, dynamic imaging has revealed that many patients continue to have residual motion at the arthrodesis.

Methods.
Forty-eight participants performed dynamic neck flexion/extension and axial rotation within a biplane radiography system 1 year following ACDF (21 one-level, 27 two-level). PRO scores included the Short Form-36, Neck Disability Index, and Cervical Spine Outcomes Questionnaire. An automated model-based tracking process matched subject-specific bone models to the biplane radiographs with sub-millimeter accuracy. Residual motion was measured across the entire arthrodesis site for both one- and two-level fusions in patients who received either allograft or autograft. Patients were divided into “pseudarthrosis” (>3° of flexion/extension residual motion) and “solid fusion” groups. Residual motion and PROs were compared between groups using Student t tests.

Results.
Patients who received allograft showed more total flexion/extension residual motion (4.1° vs. 2.8°, P = 0.12), although this failed to reach significance. No differences were noted in PROs based on graft type (all P > 0.08) or the presence of pseudarthrosis (all P > 0.13). No differences were noted in residual motion between smokers and nonsmokers (all P > 0.15); however, smokers who received allograft reported worse outcomes than nonsmokers who received allograft and smokers who received autograft.

Conclusion.
Allograft may result in slightly more residual motion at the arthrodesis site 1 year after ACDF. However, there is minimal evidence that PROs are adversely affected by slightly increased residual motion, suggesting that the current definition of pseudarthrosis correlates poorly with clinically significant findings. Additionally, autograft appears to result in superior outcomes in patients who smoke.

Level of Evidence: 2
Utilization Trends of Recombinant Human Bone Morphogenetic Protein in the United States
Authors: Kerezoudis Panagiotis , Alvi Mohammed Ali , Freedman Brett A , Nassr Ahmad , Bydon Mohamad 
Published: January 2021

Study Design
Retrospective.

Objective
The aim of this study was to explore the utilization trends of recombinant human bone morphogenetic protein (rh-BMP) in the United States using the largest inpatient administrative database.

Summary of Background Data
Since 2002, the rh-BMP has been widely used by the surgical spine community in fusion surgery. In light of the rising evidence regarding the safety and efficacy of this novel and expensive bone biological technology, a comprehensive examination of its utilization in the American population is warranted.

Methods
We queried the 2002-Q3 2015 National Inpatient Sample for patients that underwent spinal fusion with rh-BMP. We calculated population-level estimates of rh-BMP utilization trends per 100,000 spinal fusions. Trends were estimated for the overall use as well as broken down by primary versus revision fusion, fusion type, number of levels, age category, US region, and hospital type.

Results
A total of 5,563,282 fusions were performed, of which 19.9% (n = 1,108,984) utilized rh-BMP. We detected an increase in rh-BMP use in spinal fusion surgery from 0.7% in 2002 to a peak of 29.5% in 2010, followed by a gradual decline till Q3 2015, where it represented 14.7% of all fusion surgeries. These trends paralleled all fusion types. It was most commonly used in fusions spanning two to three levels. The South remained the most common region, whereas West has recently surpassed the Midwest. Its use is becoming more pervasive among older patients, particularly in the 65- to 74 years’ age group.

Conclusion
Further studies are needed to provide insights into the correlation of these trends with the technology's safety and efficacy profile in contemporary series.

Level of Evidence: 3
Responsiveness of Outcome Measures in Nonsurgical Patients with Lumbar Spinal Stenosis
Authors: Carlesso Cristiane , Piva Sara R. , Smith Clair , Ammendolia Carlo , Schneider Michael J. 
Published: January 2021

Study Design.
Secondary analysis from a randomized controlled trial on nonsurgical interventions for patients with lumbar spinal stenosis (LSS).

Objective.
The aim of this study was to assess the responsiveness of the Self-Paced Walking Test (SPWT), Swiss Spinal Stenosis Questionnaire (SSS), and Oswestry Disability Index (ODI) and determine their minimal clinically important differences (MCID) in nonsurgical LSS patients.

Summary of Background Data.
Limited information is available about the responsiveness of these tests in nonsurgical LSS population.

Methods.
A total of 180 participants completed the SPWT, SSS, and ODI at baseline, 2, and 6 months. Responsiveness was assessed by distribution-based method, including effect size and standardized response mean, and anchor-based method, using the patient global index of change (PGIC) as the external anchor to distinguish responders and non-responders. Areas under the curve (AUC) were calculated along with MCIDs for “minimal” and “moderate improvement” subgroups.

Results.
The following values represent 2- and 6-month analyses of each outcome measure, respectively. Standard effect sizes: 0.48 and 0.50 for SPWT, −0.42 and −0.36 for SSS, and −0.29 and −0.25 for ODI. Spearman correlation coefficients between PGIC and outcomes were: 0.44 and 0.39 for SPWT, −0.53 and −0.55 for SSS, and −0.46 and −0.54 for ODI. MCIDs for the “minimal improvement” subgroup were: 375.9 and 319.3 ms for SPWT, −5.3 and −5.8 points for SSS, and −9.3 and −10.8 points for ODI. AUCs was 0.68 to 0.76. MCIDs for the “moderate improvement” subgroup were: 344.2 and 538.2 m for SPWT, −5.5 and −7.5 points for SSS, and −9.1 and −13.6 points for ODI. AUCs ranged from 0.68 to 0.76.

Conclusion.
The SPWT, SSS, and ODI are responsive outcome measures to assess nonsurgical patients with LSS. This finding, along with the reported MCIDs, can help clinicians to monitor changes in their patients’ walking and physical function over time and make clinical decisions. They also provide researchers with reference for future studies in LSS.

Level of Evidence: 2
An Injectable Hyaluronic Acid Hydrogel Promotes Intervertebral Disc Repair in a Rabbit Model
Authors: Inoue Masahiro , Isa Isma Liza Mohd , Orita Sumihisa , Suzuki-Narita Miyako , Inage Kazuhide , Shiga Yasuhiro , Norimoto Masaki , Umimura Tomotaka , Sakai Takayuki , Eguchi Yawara , Watanabe Atsuya , Aoki Yasuchika , Pandit Abhay , Ohtori Seiji 
Published: January 2021

Study Design.
An in vivo model to study the effect of an injectable hyaluronic acid (HA) hydrogel following puncture-induced lumbar disc injury in rabbits.

Objectives.
The aim of this study was to determine the efficacy of an injectable HA hydrogel to maintain disc height and tissue hydration, promote structural repair, and attenuate inflammation and innervation in the lumbar discs.

Summary of Background Data.
Previously, we have demonstrated that HA hydrogel alleviated inflammation, innervation, and pain to promote disc repair. Nevertheless, the effect of an injectable HA hydrogel in the lumbar disc in a weight-bearing animal model was not performed.

Methods.
We have adopted a surgically puncture-induced disc injury at lumbar levels in a rabbit model. The discs were grouped into sham, puncture with water injection, and puncture with HA hydrogel injection. Postoperatively, we measured changes in disc height using x-ray. We used magnetic resonance imaging to assess disc degeneration on tissue hydration after euthanasia. Post-mortem, we determined histological changes, innervation (PGP9.5) and inflammation (interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]-α) in the discs.

Results.
We have demonstrated a significant reduction of disc height and T2/T1ρ mapping with histological evidence of degenerative discs, increase of innervation and inflammation in puncture-induced disc injury over time. In the HA hydrogel group, disc height was increased at weeks four and eight. A slight increase of T2 mapping, but significantly in T1ρ mapping, was observed in the HA hydrogel group at week 8. We observed homogenous NP distribution and organised AF lamellae at week eight and a slight reduced innervation score in the treatment group. HA hydrogel significantly downregulated IL-6 expression at day 1. This, however, was only slightly reduced for IL-1β and TNF-α.

Conclusion.
An injectable HA hydrogel had the protective effects in suppressing the loss of disc height, promoting tissue hydration for structural repair, and attenuating inflammation and innervation to prevent further disc degeneration.

Level of Evidence: N/A
Evaluating the Severity and Prognosis of Acute Traumatic Cervical Spinal Cord Injury
Authors: Zhu Fengzhao , Liu Yuan , Zeng Lian , Wang Yulong , Kong Xiangchuang , Yao Sheng , Chen Kaifang , Jing Xirui , Yang Lian , Guo Xiaodong 
Published: January 2021

Study Design.
Retrospective observational cohort study.

Objective.
We explored the relationship between diffusion tensor imaging (DTI) parameters and prognosis in patients with acute traumatic cervical spinal cord injury (ATCSCI).

Summary of Background Data.
DTI has been used to diagnose spinal cord injury; nevertheless, its role remains controversial.

Methods.
We analyzed retrospectively 24 patients with ATCSCI who were examined using conventional T2-weighted imaging and DTI. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were recorded at the injured site. Diffusion tensor tractography (DTT) was used to measure the spinal cord white matter fiber volume (MWFV). American Spinal Injury Association (ASIA) grades were recorded. Correlations between DTI parameters and ASIA scores were evaluated using Spearman correlation coefficients.

Results.
FA values at injured sites were significantly lower than those of the control group, whereas ADC values in injured and control groups were not significantly different. DTT revealed that ATCSCI could be divided into four types: Type A1—complete rupture of spinal cord white matter fiber (MWF); Type A2—partial rupture of MWF; Type B—most MWF retained with severe compression or abnormal fiber conduction direction; and Type C—MWF basically complete with slight compression. Preoperative physical examinations revealed complete injury (ASIA A) in patients with A1 (n = 4) and A2 (n = 4). The ASIA grades or scores of A2 were improved to varying degrees, whereas there was no significant improvement in A1. FA values and MWFV of ASIA B, C, and D were significantly higher than those of ASIA A. FA and MWFV were correlated with ASIA motor score preoperatively and at final follow-up.

Conclusion.
We propose a classification for the severity of ATCSCI based on DTI and DTT that may explain why some patients with ASIA A recover, whereas others do not.

Level of Evidence: 4
Patient Outcomes After Single-level Coflex Interspinous Implants Versus Single-level Laminectomy
Authors: Zhong Jack , O’Connell Brooke , Balouch Eaman , Stickley Carolyn , Leon Carlos , O’Malley Nicholas , Protopsaltis Themistocles S. , Kim Yong H. , Maglaras Constance , Buckland Aaron J. 
Published: January 2021

Study Design
Retrospective cohort analysis.

Objective
The aim of this study was to compare postoperative outcomes of Coflex interspinous device versus laminectomy.

Summary of Background Data
Coflex Interlaminar Stabilization device (CID) is indicated for one- or two-level lumbar stenosis with grade 1 stable spondylolisthesis in adult patients, as an alternative to laminectomy, or laminectomy and fusion. CID provides stability against progressive spondylolisthesis, retains motion, and prevents further disc space collapse.

Methods
Patients ≥18 years’ old with lumbar stenosis and grade 1 stable spondylolisthesis who underwent either primary single-level decompression and implantation of CID, or single-level laminectomy alone were included with a minimum 90-day follow-up at a single academic institution. Clinical characteristics, perioperative outcomes, and postoperative complications were reviewed until the latest follow-up. χ
2 and independent samples t tests were used for analysis.

Results
Eighty-three patients (2007–2019) were included: 37 cases of single-level laminectomy (48.6% female) were compared to 46 single-level CID (50% female). CID cohort was older (CID 69.0 ± 9.4 vs. laminectomy 64.2 ± 11.0, P = 0.042) and had higher American Society of Anesthesiologists (ASA) grade (CID 2.59 ± 0.73 vs. laminectomy 2.17 ± 0.48, P = 0.020). CID patients had higher estimated blood loss (EBL) (97.50 ± 77.76 vs. 52.84 ± 50.63 mL, P = 0.004), longer operative time (141.91 ± 47.88 vs. 106.81 ± 41.30 minutes, P = 0.001), and longer length of stay (2.0 ± 1.5 vs. 1.1 ± 1.0 days, P = 0.001). Total perioperative complications (21.7% vs. 5.4%, P = 0.035) and instrumentation-related complication was higher in CID (10.9% vs. 0% laminectomy group, P = 0.039). There were no other significant differences between the groups in demographics or outcomes.

Conclusion
Single-level CID devices had higher perioperative 90-day complications, longer operative time, length of stay, higher EBL compared to laminectomies alone. Similar overall revision and neurologic complication rates were noted compared to laminectomy at last follow-up.

Level of Evidence: 3
MAPK blockade, toxicities, pathogenesis and management
Authors: Moreira Alvaro , Lebbé Céleste , Heinzerling Lucie 
Published: January 2021

Purpose of review
BRAF/MEK inhibitor has changed the treatment landscape in patients with advanced and metastatic melanoma with prolonged overall survival and progression-free survival. Since three treatment combinations exist with similar efficacy therapy decisions are often made based on the side effect profile. Additionally, on-target side effects or class effects have to be properly managed to ensure treatment adherence.

Recent findings
Sequential treatment with BRAF/MEK inhibition and immunotherapy might increase toxicity with a sepsis-like syndrome and triple therapy with concomitant BRAF/MEK inhibition and anti-PD1/PD-L1 antibody therapy induces severe side effects in the vast majority of patients.

Summary
Toxicity of combination therapy with BRAF/MEK inhibitors is generally manageable, reversible and infrequently associated with treatment discontinuation. In case of persisting off-target effects the change to another combination therapy can resolve side effects.
MEK inhibitors in RASopathies
Authors: Bergqvist Christina , Wolkenstein Pierre 
Published: January 2021

Purpose of review
An early understanding of the role of the Ras/Raf/MEK/ERK signalling pathway in regulating cell proliferation has set the stage for the development of several potent and selective MEK inhibitors (MEKi). MEKi represent promising therapies for RAS-driven neoplasias and RASopathies associated with increased Ras/MAPK activity.

Recent findings
Neurofibromatosis 1 (NF1) is a prototypic RASopathy in which early-phase clinical trials with MEKi have been successful in the treatment of plexiform neurofibromas (pNF) and low-grade gliomas (LGGs). The phase 2 trial (SPRINT) of selumetinib in pNF resulted in at least 20% reduction in the size of pNF from baseline in 71% of patients and was associated with clinically meaningful improvements. On the basis of this trial, selumetinib (Koselugo) received FDA approval for children 2 years of age and older with inoperable, symptomatic pNF. The phase 2 trial of selumetinib in LGG resulted in 40% partial response and 96% of patients had 2 years of progression-free survival.

Summary
Given the potential of MEK inhibition as an effective and overall well tolerated medical treatment, the use of targeted agents in the NF1 population is likely to increase considerably. Future work on non-NF1 RASopathies should focus on developing preclinical models and defining endpoints for measurement of efficacy in order to conduct clinical trials.