bluuebunny/crossref_metadata_2025_split huggingface dataset:
VITamin D and OmegA-3 TriaL (VITAL): Effects of Vitamin D Supplements on Risk of Falls in the US Population
Authors: LeBoff Meryl S , Murata Elle M , Cook Nancy R , Cawthon Peggy , Chou Sharon H , Kotler Gregory , Bubes Vadim , Buring Julie E , Manson JoAnn E 
Published: June 2020

Abstract

Context
It is unclear whether vitamin D supplementation reduces risk of falls, and results from randomized controlled trials (RCTs) are conflicting.

Objective
The objective of this work is to determine whether 2000 IU/day of supplemental vitamin D3 decreases fall risk.

Design
VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, placebo-controlled RCT including 25 871 adults, randomly assigned November 2011 to March 2014 and treated for 5.3 years (median).

Setting
This is a nationwide study.

Participants
Men 50 years or older and women 55 years or older (mean age, 67.1 years) without cancer or cardiovascular disease at baseline participated in this study.

Interventions
Interventions included vitamin D3 (cholecalciferol; 2000 IU/day) and/or omega-3 fatty acids (1 g/day) or respective placebos in a 2 × 2 factorial design.

Main Outcome Measures
Main outcome measures include 2 or more falls and falls resulting in a doctor or hospital visit.

Results
Baseline serum total 25-hydroxyvitamin D (25[OH]D) level was 77 nmol/L; characteristics were well-balanced between groups. Numbers of participants with 2 or more falls were similar between active and placebo groups (9.8% vs 9.4%). Over 5 years, there were no differences in the proportion having 2 or more falls (odds ratio [OR] = 0.97; 95% CI, 0.90-1.05, P = .50), falls resulting in a doctor visit (OR = 1.03; 95% CI, 0.94-1.13, P = .46), or resulting in a hospital visit (OR = 1.04; 95% CI, 0.90-1.19, P = .61) between groups. Results did not differ between those with baseline 25(OH)D less than 50 vs 50 nmol/L or greater or other cut points.

Conclusion
Daily supplemental vitamin D3 vs placebo did not decrease fall risk in generally healthy adults not selected for vitamin D insufficiency. This large RCT does not indicate that supplemental vitamin D should be used for primary prevention of falls in the US population.
Brn3a/Pou4f1 Functions as a Tumor Suppressor by Targeting c-MET/STAT3 Signaling in Thyroid Cancer
Authors: Jung Seung-Nam , Kang Yea Eun , Lee Gun Ho , Liu Lihua , Oh Chan , Jin Yan Li , Lim Mi Ae , Lee Kyungmin , Oh Taejeong , Won Ho-Ryun , Chang Jae Won , Koo Bon Seok 
Published: May 2020

Abstract

Background
Brn3a/Pou4f1 is a class IV POU domain-containing transcription factor and has been found to be expressed in a variety of cancers. However, the mechanism and action of Brn3a in thyroid cancer has not been investigated.

Purpose
To investigate the role of Brn3a in thyroid cancer progression and its clinical implication.

Methods
We examined Brn3a expression status in patients with thyroid cancer and analyzed relationships between Brn3a expression and clinicopathological findings using The Cancer Genome Atlas (TCGA) database. For functional in vitro analysis, proliferation, migration, invasion assay, and Western blotting were performed after overexpression or suppression of Brn3a.

Results
The promoter hypermethylation of Brn3a was found in patients with aggressive thyroid cancer and Brn3a was downregulated in tissues of patients with thyroid cancer. In TCGA database, the low-Brn3a-expression group revealed a more aggressive phenotype, including T stage and extrathyroid extension when compared with the high-Brn3a-expression group. Overexpression of Brn3a suppressed cell migration and invasion via regulation of epithelial-mesenchymal transition (EMT)-associated proteins in thyroid cancer cell lines. Brn3a overexpression also downregulated signal transducer and activator of transcription 3 (STAT3) signaling through suppression of tyrosine-protein kinase Met (c-MET). In contrast, knockdown of Brn3a by small interfering ribonucleic acid (siRNA) significantly increased cell migration and invasion through upregulation of c-MET/STAT3. These results imply that Brn3a suppresses tumor metastasis via c-MET/STAT3 inhibition and EMT suppression in thyroid cancer.

Conclusions
Our findings show that Brn3a is a potential tumor suppressor that leads to reduced cancer cell migration and invasion in thyroid cancer. Elucidation of the Brn3a-regulated cancer pathways may therefore provide novel therapeutic strategies to control thyroid cancer metastasis.
Biomarkers of Bone Turnover Identify Subsets of Chronic Kidney Disease Patients at Higher Risk for Fracture
Authors: Hughes-Austin Jan M , Katz Ronit , Semba Richard D , Kritchevsky Stephen B , Bauer Douglas C , Sarnak Mark J , Ginsberg Charles , Shlipak Michael G , Lima Florence , Malluche Hartmut H , Ix Joachim H 
Published: May 2020

AbstractBackgroundWe sought to identify biomarkers that indicate low turnover on bone histomorphometry in chronic kidney disease (CKD) patients, and subsequently determined whether this panel identified differential risk for fractures in community-dwelling older adults.MethodsAmong CKD patients who underwent iliac crest bone biopsies and histomorphometry, we evaluated candidate biomarkers to differentiate low turnover from other bone disease. We applied this biomarker panel to 641 participants in the Health Aging and Body Composition Study (Health ABC) study with estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 who were followed for fracture. Cox proportional hazards models evaluated the association of bone mineral density (BMD) with fracture risk and determined whether biomarker-defined low bone turnover modified fracture risk at any level of BMD.ResultsIn 39 CKD patients age 64 ± 13 years, 85% female, with mean eGFR 37 ± 14 mL/min/1.73 m2 who underwent bone biopsy, lower fibroblast growth factor (FGF)-23, higher ɑ-Klotho, and lower parathyroid hormone (PTH) indicated low bone turnover in accordance with bone histomorphometry parameters (individual area under the curve = 0.62, 0.73, and 0.55 respectively; sensitivity = 22%, specificity = 100%). In Health ABC, 641 participants with CKD were age 75 ± 3 years , 49% female, with mean eGFR 48 ± 10 mL/min/1.73 m2. For every SD lower hip BMD at baseline, there was an 8-fold higher fracture risk in individuals with biomarker-defined low turnover (hazard ratio 8.10 [95% CI, 3.40-19.30]) vs a 2-fold higher risk in the remaining individuals (hazard ratio 2.28 [95% CI, 1.69-3.08]) (Pinteraction = .082).ConclusionsIn CKD patients who underwent bone biopsy, lower FGF-23, higher ɑ-Klotho, and lower PTH together had high specificity for identifying low bone turnover. When applied to older individuals with CKD, BMD was more strongly associated with fracture risk in those with biomarker-defined low turnover.
Contemporary Thyroid Nodule Evaluation and Management
Authors: Grani Giorgio , Sponziello Marialuisa , Pecce Valeria , Ramundo Valeria , Durante Cosimo 
Published: June 2020

Abstract

Context
Approximately 60% of adults harbor 1 or more thyroid nodules. The possibility of cancer is the overriding concern, but only about 5% prove to be malignant. The widespread use of diagnostic imaging and improved access to health care favor the discovery of small, subclinical nodules and small papillary cancers. Overdiagnosis and overtreatment is associated with potentially excessive costs and nonnegligible morbidity for patients.

Evidence Acquisition
We conducted a PubMed search for the recent English-language articles dealing with thyroid nodule management.

Evidence Synthesis
The initial assessment includes an evaluation of clinical risk factors and sonographic examination of the neck. Sonographic risk-stratification systems (e.g., Thyroid Imaging Reporting and Data Systems) can be used to estimate the risk of malignancy and the need for biopsy based on nodule features and size. When cytology findings are indeterminate, molecular analysis of the aspirate may obviate the need for diagnostic surgery. Many nodules will not require biopsy. These nodules and those that are cytologically benign can be managed with long-term follow-up alone. If malignancy is suspected, options include surgery (increasingly less extensive), active surveillance or, in selected cases, minimally invasive techniques.

Conclusion
Thyroid nodule evaluation is no longer a 1-size-fits-all proposition. For most nodules, the likelihood of malignancy can be confidently estimated without resorting to cytology or molecular testing, and low-frequency surveillance is sufficient for most patients. When there are multiple options for diagnosis and/or treatment, they should be discussed with patients as frankly as possible to identify an approach that best meets their needs.
Fixation of the short global tissue-sparing hip stem
Authors: Nieuwenhuijse Marc J. , Vehmeijer Stephan B. W. , Mathijsen Nina M. C. , Keizer Stefan B. 
Published: May 2020

AimsShort, bone-conserving femoral components are increasingly used in total hip arthroplasty (THA). They are expected to allow tissue-conserving implantation and to render future revision surgery more straightforward but the long-term data on such components is limited. One such component is the global tissue-sparing (GTS) stem. Following the model for stepwise introduction of new orthopaedic implants, we evaluated early implant fixation and clinical outcome of this novel short-stem THA and compared it to that of a component with established good long-term clinical outcome.MethodsIn total, 50 consecutive patients ≤ 70 years old with end-stage symptomatic osteo-arthritis were randomized to receive THA with the GTS stem or the conventional Taperloc stem using the anterior supine intermuscular approach by two experienced hip surgeons in two hospitals in the Netherlands. Primary outcome was implant migration. Patients were followed using routine clinical examination, patient reported outcome using Harris Hip Score (HHS), Hip Disability And Osteoarthritis Outcome Score (HOOS), EuroQol five-dimension questionnaire (EQ5D), and Roentgen Stereophotogrammetric Analysis (RSA) at three, six, 12, and 24 months. This study evaluated the two-year follow-up results.ResultsIn addition to the initial migration pattern of distal migration (subsidence, Y-translation) and retroversion (Y-rotation) also exhibited by the Taperloc stem, the GTS stem showed an initial migration pattern of varization (X-translation combined with Z-rotation) and posterior translation (Z-translation). However, all components stabilized aside from one Taperloc stem which became loose secondary to malposition and was later revised. Clinical outcomes and complications were not statistically significantly different with the numbers available.ConclusionA substantially different and more extensive initial migration pattern was seen for the GTS stem compared to the Taperloc stem. Although implant stabilization was achieved, excellent long-term survival similar to that of the Taperloc stem should not be inferred. Especially in the absence of clinically proven relevant improvement, widespread usage should be postponed until long-term safety has been established. Cite this article: Bone Joint J 2020;102-B(6):699–708.
Impact of chemotherapy-induced necrosis on event-free and overall survival after preoperative MAP chemotherapy in patients with primary high-grade localized osteosarcoma
Authors: Tsuda Yusuke , Tsoi Kim , Parry Michael C. , Stevenson Jonathan D. , Fujiwara Tomohiro , Sumathi Vaiyapuri , Jeys Lee M. 
Published: May 2020

Aims To assess the correlation between the histological response to preoperative chemotherapy and event-free survival (EFS) or overall survival (OS) in patients with high-grade localized osteosarcoma. Methods Out of 625 patients aged ≤ 40 years treated for primary high-grade osteosarcoma between 1997 and 2016, 232 patients without clinically detectable metastases at the time of diagnosis and treated with preoperative high-dose methotrexate, adriamycin and cisplatin (MAP) chemotherapy and surgery were included. Associations of chemotherapy-induced necrosis in the resected specimen and EFS or OS were assessed using Cox model and the Pearson’s correlation coefficients (r). Time-dependent receiver operating characteristic analysis was applied to determine the optimal cut-off value of chemotherapy-induced necrosis for EFS and OS. Results OS was 74% (95% confidence interval (CI) 67 to 79) at five years. Median chemotherapy-induced necrosis was 85% (interquartile range (IQR) 50% to 97%). In multivariate Cox model, chemotherapy-induced necrosis was significantly associated with EFS and OS (hazard ratio (HR) = 0.99 (95% CI 0.98 to 0.99); p < 0.001 and HR = 0.98 (95% CI 0.97 to 0.99); p < 0.001, respectively). Positive correlation was observed between chemotherapy-induced necrosis and five-year EFS and five-year OS (r = 0.91; p < 0.001, and r = 0.85; p < 0.001, respectively). The optimal cut-off value of chemotherapy-induced necrosis for five-year EFS and five-year OS was 85% and 72%, respectively. Conclusion Chemotherapy-induced necrosis in the resected specimen showed positive correlation with EFS and OS in patients with high-grade localized osteosarcoma after MAP chemotherapy. In our analysis, optimal cut-off values of MAP chemotherapy-induced necrosis in EFS and OS were lower than the commonly used 90%, suggesting the need for re-evaluation of the optimal cut-off value through larger, international collaborative research. Cite this article: Bone Joint J 2020;102-B(6):795–803.
Outcomes of modular femoral revision implants and the effect of component design on subsidence
Authors: Abdelsamie Karam R. , Elhawary Ibrahim , Ali Hesham , Ali Mohamed , EL-Shafie Mohamed , Dominic Meek R. M. 
Published: May 2020

AimsFemoral revision component subsidence has been identified as predicting early failure in revision hip surgery. This comparative cohort study assessed the potential risk factors of subsidence in two commonly used femoral implant designs.MethodsA comparative cohort study was undertaken, analyzing a consecutive series of patients following revision total hip arthroplasties using either a tapered-modular (TM) fluted titanium or a porous-coated cylindrical modular (PCM) titanium femoral component, between April 2006 and May 2018. Clinical and radiological assessment was compared for both treatment cohorts. Risk factors for subsidence were assessed and compared.ResultsIn total, 65 TM and 35 PCM cases were included. At mean follow-up of seven years (1 to 13), subsidence was noted in both cohorts during the initial three months postoperatively (p < 0.001) then implants stabilized. Subsidence noted in 58.7% (38/65 cases) of the TM cohort (mean 2.3 mm, SD 3.5 mm) compared to 48.8% (17/35) of PCM cohort (mean 1.9 mm, SD 2.6 mm; p = 0.344). Subsidence of PCM cohort were significantly associated with extended trochanteric osteotomy (ETO) (p < 0.041). Although the ETO was used less frequently in PCM stem cohort (7/35), subsidence was noted in 85% (6/7) of them. Significant improvement of the final mean Oxford Hip Score (OHS) was reported in both treatment groups (p < 0.001).ConclusionBoth modular TM and PCM revision femoral components subsided within the femur. TM implants subsided more frequently than PCM components if the femur was intact but with no difference in clinical outcomes. However, if an ETO is performed then a PCM component will subside significantly more and suggests the use of a TM implant may be advisable. Cite this article: Bone Joint J 2020;102-B(6):709–715.
2020 John N. Insall Award: Removal of total knee arthroplasty from the inpatient-only list adversely affects bundled payment programmes
Authors: Yayac Michael , Schiller Nicholas , Austin Matthew S. , Courtney P. Maxwell 
Published: May 2020

Aims The purpose of this study was to determine the impact of the removal of total knee arthroplasty (TKA) from the Medicare Inpatient Only (IPO) list on our Bundled Payments for Care Improvement (BPCI) Initiative in 2018. Methods We examined our institutional database to identify all Medicare patients who underwent primary TKA from 2017 to 2018. Hospital inpatient or outpatient status was cross-referenced with Centers for Medicare & Medicaid Services (CMS) claims data. Demographics, comorbidities, and outcomes were compared between patients classified as ‘outpatient’ and ‘inpatient’ TKA. Episode-of-care BPCI costs were then compared from 2017 to 2018. Results Of the 2,135 primary TKA patients in 2018, 908 (43%) were classified as an outpatient and were excluded from BPCI. Inpatient classified patients had longer mean length of stay (1.9 (SD 1.4) vs 1.4 (SD 1.7) days, p < 0.001) and higher rates of discharge to rehabilitation (17% vs 3%, p < 0.001). Post-acute care costs increased when comparing the BPCI patients from 2017 to 2018, ($5,037 (SD $7,792) vs $5793 (SD $8,311), p = 0.010). The removal of TKA from the IPO list turned a net savings of $53,805 in 2017 into a loss of $219,747 in 2018 for our BPCI programme. Conclusions Following the removal of TKA from the IPO list, nearly half of the patients at our institution were inappropriately classified as an outpatient. Our target price was increased and our institution realized a substantial loss in 2018 BPCI despite strong quality metrics. CMS should address its negative implications on bundled payment programmes. Cite this article: Bone Joint J 2020;102-B(6 Supple A):19–23.
Reflecting on and managing the emotional impact of prosthetic joint infections on orthopaedic surgeons—a qualitative study
Authors: Svensson Karin , Rolfson Ola , Mohaddes Maziar , Malchau Henrik , Erichsen Andersson Annette 
Published: May 2020

Aims To investigate the experience and emotional impact of prosthetic joint infection (PJI) on orthopaedic surgeons and identify holistic strategies to improve the management of PJI and protect surgeons’ wellbeing. Methods In total, 18 prosthetic joint surgeons in Sweden were recruited using a purposive sampling strategy. Content analysis was performed on transcripts of individual in-person interviews conducted between December 2017 and February 2018. Results PJI had a negative emotional impact on Swedish surgeons. Many felt guilt, stress, and a sense of failure, and several aspects of PJI management were associated with psychosocial challenges. Peer support was reported as the most important coping strategy as was collaborating with infectious disease specialists. Conclusion Our study affirms that there is a negative emotional impact of PJI on surgeons which can be minimized by improved peer support and working in multidisciplinary teams. Based on the surgeons’ experiences we have identified desired improvements that may facilitate the management of PJI. These may also be applicable within other surgical specialties dealing with postoperative infections, but need to be evaluated for their efficacy. Cite this article: Bone Joint J 2020;102-B(6):736–743.
Is a full component revision necessary for isolated tibial loosening?
Authors: Martin J. Ryan , Geary Michael B. , Ransone Michael , Macknet David , Fehring Keith , Fehring Thomas 
Published: May 2020

AimsAseptic loosening of the tibial component is a frequent cause of failure in primary total knee arthroplasty (TKA). Management options include an isolated tibial revision or full component revision. A full component revision is frequently selected by surgeons unfamiliar with the existing implant or who simply wish to “start again”. This option adds morbidity compared with an isolated tibial revision. While isolated tibial revision has a lower morbidity, it is technically more challenging due to difficulties with exposure and maintaining prosthetic stability. This study was designed to compare these two reconstructive options.MethodsPatients undergoing revision TKA for isolated aseptic tibial loosening between 2012 and 2017 were identified. Those with revision implants or revised for infection, instability, osteolysis, or femoral component loosening were excluded. A total of 164 patients were included; 88 had an isolated tibial revision and 76 had revision of both components despite only having a loose tibial component. The demographics and clinical and radiological outcomes were recorded.ResultsThe patient demographics were statistically similar in the two cohorts. The median follow-up was 3.5 years (interquartile range (IQR) 1 to 12.5). Supplementary femoral metaphyseal fixation was required in five patients in the full revision cohort. There was a higher incidence of radiological tibial loosening in the full component revision cohort at the final follow-up (8 (10.5%) vs 5 (5.7%); p = 0.269). Three patients in the full component revision cohort developed instability while only one in the isolated tibial cohort did. Three patients in the full revision cohort developed a flexion contracture greater than 5° while none in the isolated tibial cohort did.ConclusionIsolated tibial revision for aseptic tibial loosening has statistically similar clinical and radiological outcomes at a median follow-up of 3.5 years, when compared with full component revision. Substantial bone loss can occur when removing a well-fixed femoral component necessitating a cone or sleeve. Femoral component revision for isolated tibial loosening can frequently be avoided provided adequate ligamentous stability can be obtained. Cite this article: Bone Joint J 2020;102-B(6 Supple A):123–128.
Patterns of cartilage loss and anterior cruciate ligament status in end-stage osteoarthritis of the knee
Authors: Scott Chloe E. H. , Holland George , Krahelski Oliver , Murray Iain R. , Keating John F. , Keenan Oisin J. F. 
Published: May 2020

Aims This study aims to determine the proportion of patients with end-stage knee osteoarthritis (OA) possibly suitable for partial (PKA) or combined partial knee arthroplasty (CPKA) according to patterns of full-thickness cartilage loss and anterior cruciate ligament (ACL) status. Methods A cross-sectional analysis of 300 consecutive patients (mean age 69 years (SD 9.5, 44 to 91), mean body mass index (BMI) 30.6 (SD 5.5, 20 to 53), 178 female (59.3%)) undergoing total knee arthroplasty (TKA) for Kellgren-Lawrence grade ≥ 3 knee OA was conducted. The point of maximal tibial bone loss on preoperative lateral radiographs was determined as a percentage of the tibial diameter. At surgery, Lachman’s test and ACL status were recorded. The presence of full-thickness cartilage loss within 16 articular surface regions (two patella, eight femoral, six tibial) was recorded. Results According to articular cartilage loss and ACL status, 195/293 (67%) were suitable for PKA or CPKA: medial unicompartmental knee arthroplasty (UKA) 97/293 (33%); lateral UKA 25 (9%); medial bicompartmental arthroplasty 31 (11%); lateral bicompartmental arthroplasty 12 (4%); bicondylar-UKA 23 (8%); and patellofemoral arthroplasty (PFA) seven (2%). The ACL was intact in 166 (55%), frayed in 82 (27%), disrupted in 12 (4%), and absent in 33 (11%). Lachman testing was specific (97%) but poorly sensitive (38%) for disrupted/absent ACLs. The point of maximal tibial bone loss showed good interclass correlation (ICC 0.797, 0.73 to 0.85 95% confidence interval (CI); p < 0.001) and was more posterior when the ACL was absent. Maximum tibial bone loss occurring at > 55% of the anterior to posterior distance predicted ACL absence with 93% sensitivity and 91% specificity (area under the curve 0.97 (0.94 to 0.99 95% CI; p < 0.001). Conclusion ACL status can be reliably determined from a lateral radiograph using the location of maximal tibial bone loss. According to regions of cartilage loss and ACL status, two-thirds of patients with end-stage knee OA could potentially be treated with PKA or CPKA. Cite this article: Bone Joint J 2020;102-B(6):716–726.