Orthogeriatric co-management for proximal femoral fractures. Can two additions make a big difference?
- 作者列表："Maic Werner","Olaf Krause","Christian Macke","Lambert Herold","Alexander Ranker","Christian Krettek","Emmanouil Liodakis
Abstract Background Proximal femoral fractures are a major socioeconomic burden and they occur mainly in geriatric patients. High mortality and complication rates are reported. To reduce the mortality and morbidity of these patients, co-management with geriatricians has been recommended. Most previous studies have focused on relatively comprehensive care models. Models with only a few additions to the usual care have not been extensively evaluated. Methods This retrospective observational study included all patients aged ≥70 years (mean age: 84.5 ± 7.1 years, 70% women) with an isolated proximal femoral fracture treated surgically in our institution from May 2018 to October 2019. In the first 9 months, patients were treated with the usual care (control group, n = 103). In the second 9 months, patients were treated with our multidisciplinary care model (intervention group, n = 104), which included the usual care, plus: (1) one multidisciplinary ward round per week and (2) one “elective” operation slot per day reserved for proximal femoral fractures. Baseline characteristics and outcome measures of the hospital stay were extracted from electronic health records. A 3-month follow-up was conducted by phone. Results Baseline characteristics were comparable between groups (p > 0.05). The hospital stay was shorter in the intervention group than in the control group (7.8 ± 4.3 vs. 9.1 ± 4.5; p = 0.022). The intervention reduced the waiting time for surgery by more than 10 h (intervention: 25.4 ± 24.5 vs. control: 35.8 ± 34.1 h; p = 0.013). A structured phone interview was not performed in 30.9% of the cases. The model reduced the overall dissatisfaction rate by more than half (12.9% vs. 32.4%; p = 0.008). On the other hand, the groups had similar perioperative complication rates (25% vs. 24.3%; p > 0.9999) and mortality (4.8% vs. 3.9%; p > 0.9999) and they remained similar at the 3-month follow-up (complications: 20.3% vs. 17.6% p = 0.831, mortality: 18.2% vs. 15.0% p = 0.573). Conclusion We found that two additions to the usual proximal femoral fracture regimen could significantly improve the overall satisfaction rate, reduce the length of hospital stay and shorten the waiting time for surgery. In contrast to previous studies, we observed no significant improvements in complication or mortality rates. Further changes in the standard care might be needed for this purpose.
背景股骨近端骨折是一个主要的社会经济负担，主要发生在老年患者。报告了高死亡率和并发症发生率。为了降低这些患者的死亡率和发病率，建议与老年病学家共同管理。大多数以前的研究都集中在相对全面的护理模式。只有少数添加到常规护理的模型尚未得到广泛评价。方法本回顾性观察性研究包括所有年龄 ≥ 70 岁的患者 (平均年龄: 84.5 ± 7.1 岁，70% 为女性)。2018 年 5 月至 2019 年 10 月在我机构手术治疗的孤立性股骨近端骨折。在治疗前 9 个月内，患者接受常规护理 (对照组，n = 103)。在第二个 9 个月，患者接受我们的多学科护理模式 (干预组，n = 104)，其中包括常规护理，加上 :( 1) 每周一次多学科查房，(2) 每天为股骨近端骨折保留一个 “择期” 手术槽。从电子健康档案中提取住院时间的基线特征和结局指标。电话随访 3 个月。结果基线特征在组间具有可比性 (p> 0.05)。干预组住院时间短于对照组 (7.8 ± 4.3 vs. 9.1 ± 4.5; P = 0.022)。干预使手术等待时间缩短 10 h 以上 (干预: 25.4 ± 24.5 vs. control: 35.8 ± 34.1 h; P = 0.013)。30.9% 的病例没有进行结构化电话访谈。该模型将总体不满意率降低了一半以上 (12.9% vs. 32.4%; P = 0.008)。另一方面，各组的围手术期并发症发生率相似 (25% vs. 24.3%; P> 0.9999) 和死亡率 (4.8% vs. 3.9%; P> 0.9999)，3 个月随访时仍相似 (并发症: 20.3% vs. 17.6% p = 0.831，死亡率: 18.2% vs. 15.0% p = 0.573)。结论我们发现在常规股骨近端骨折方案中增加两种方案可显著提高总体满意率，减少住院时间，缩短等待手术时间。与以前的研究相比，我们观察到并发症或死亡率没有显著改善。为此，可能需要进一步改变标准护理。
METHODS::A major challenge in translating findings from genome-wide association studies (GWAS) to biological mechanisms is pinpointing functional variants because only a very small percentage of variants associated with a given trait actually impact the trait. We used an extensive epigenetics, transcriptomics, and genetics analysis of the TBX15/WARS2 neighbourhood to prioritize this region's best-candidate causal variants for the genetic risk of osteoporosis (estimated bone density, eBMD) and obesity (waist-hip ratio or waist circumference adjusted for body mass index). TBX15 encodes a transcription factor that is important in bone development and adipose biology. Manual curation of 692 GWAS-derived variants gave eight strong candidates for causal SNPs that modulate TBX15 transcription in subcutaneous adipose tissue (SAT) or osteoblasts, which highly and specifically express this gene. None of these SNPs were prioritized by Bayesian fine-mapping. The eight regulatory causal SNPs were in enhancer or promoter chromatin seen preferentially in SAT or osteoblasts at TBX15 intron-1 or upstream. They overlap strongly predicted, allele-specific transcription factor binding sites. Our analysis suggests that these SNPs act independently of two missense SNPs in TBX15. Remarkably, five of the regulatory SNPs were associated with eBMD and obesity and had the same trait-increasing allele for both. We found that WARS2 obesity-related SNPs can be ascribed to high linkage disequilibrium with TBX15 intron-1 SNPs. Our findings from GWAS index, proxy, and imputed SNPs suggest that a few SNPs, including three in a 0.7-kb cluster, act as causal regulatory variants to fine-tune TBX15 expression and, thereby, affect both obesity and osteoporosis risk.
METHODS:PURPOSE:Systemic mastocytosis (SM) is characterized by the expansion of clonal mast cells that infiltrate various organ systems. The extent of organ infiltration and subsequent organ damage distinguishes between indolent SM (ISM) defined by a nearly normal life expectancy and advanced SM (AdvSM) defined by poor prognosis. In ISM, measurement of the bone mineral density (BMD) frequently reveals osteoporosis. In contrast, the clinical implication of an increased BMD and osteosclerosis remains unclear. METHODS:BMD was evaluated in 61 patients with mastocytosis (ISM, n = 29, 48%; AdvSM, n = 32, 52%). We correlated the prevalence of osteoporosis, increased BMD and osteosclerosis with clinical parameters, disease variant and prognosis. RESULTS:Osteoporosis was detected in 11/29 (38%) patients with ISM but only in 2/32 (6%) patients with AdvSM (p = 0.004). An increased BMD was detected in 1/29 (3%) patients with ISM and 24/32 (75%) patients with AdvSM (p < 0.001) while osteosclerosis was only detected in AdvSM patients (16/32, 50%). AdvSM patients with increased BMD had higher levels of bone marrow mast cell infiltration, higher serum tryptase and alkaline phosphatase levels compared to ISM as well as higher number of high-molecular risk mutations (p < 0.05). In addition, we found that the prognosis of AdvSM patients with increased BMD is inferior compared to those without increased BMD (median overall survival 3.6 years versus not reached, p = 0.031). CONCLUSIONS:Osteoporosis is a common feature in ISM but not in AdvSM. An increased BMD is frequently present in AdvSM but not in ISM and is associated with more advanced disease and inferior outcome.
METHODS::We present salmon calcitonin (SCT) loaded Hydroxyapatite nanoparticles (HAP-NPs) for sublingual osteoporosis therapy. Surface stabilized HAP-NPs were prepared by aqueous precipitation. SCT was loaded by ionic complexation, as confirmed by FTIR. SCT-HAP-NPs exhibited high loading efficiency (~85%), average size (~100nm), and zeta potential (~-25 mv). Stability of SCT was established by circular dichroism spectroscopy and HPLC analysis. Confocal laser scanning microscopy confirmed deep penetration of SCT-HAP-NPs into the mucosa with >4-fold enhancement in permeability relative to SCT solution. Sublingual SCT-HAP-NPs revealed relative bioavailability of ~15% compared to the subcutaneous injection in rabbits (200iu). Significant and comparable improvement in serum biomarkers with increase in bone mass and mechanical strength and decreased bone erosion compared to subcutaneous SCT was confirmed in ovariectomized (OVX) osteoporosis rat model. Such comparable pharmacodynamic effect at the same dose suggested targeted bone delivery and promise of sublingual SCT-HAP-NPs as a non-invasive alternative to the injection.