Intraoperative frozen section histopathology for the diagnosis of periprosthetic joint infection in hip revision surgery: the influence of recent dislocation and/or periprosthetic fracture.
- 作者列表："Luyckx L","Somers JFA","Cokelaere K","Deloose S","Delrue G","Hermans L
AIMS:To evaluate the accuracy of intraoperative frozen section histopathology for diagnosing periprosthetic joint infection (PJI) during hip revision surgery, both for patients with and without recent trauma to the hip. PATIENTS AND METHODS:The study included all revision total hip replacement procedures where intraoperative frozen section histopathology had been used for the evaluation of infection in a single institution between 2008 and 2015. Musculoskeletal Infection Society criteria were used to define infection. 210 hips were included for evaluation. Prior to revision surgery, 36 hips had a dislocation or a periprosthetic fracture (group A), and 174 did not (group B). RESULTS:The prevalence of infection was 14.3% (5.6% in group A and 16.1% in group B). Using Feldman criteria, the sensitivity of histopathology was 50.0%, specificity 47.1%, positive predictive value 5.3% and negative predictive value 94.1% in group A. The sensitivity of frozen section histopathology was 75.0%, specificity 96.5%, positive predictive value 85% and negative predictive value 95.3% in group B. CONCLUSIONS:Intraoperative frozen section histopathology is reliable for the diagnosis of PJI if no dislocation or periprosthetic fracture has occurred prior to hip revision surgery.
目的: 评价术中冰冻切片组织病理学诊断髋关节翻修手术中假体周围关节感染 (PJI) 的准确性，无论是对髋关节有无近期创伤的患者。 患者和方法: 该研究包括所有翻修全髋关节置换手术，其中在 2008 年至 2015 年间，术中冰冻切片组织病理学已用于单个机构的感染评估。采用肌肉骨骼感染学会标准定义感染。纳入 210 髋进行评价。翻修手术前，36 髋有脱位或假体周围骨折 (a 组)，174 髋无脱位或假体周围骨折 (B 组)。 结果: 感染率 14.3% (A 组 5.6%，B 组 16.1%)。使用 Feldman 标准，A 组组织病理学的敏感性为 50.0%，特异性为 47.1%，阳性预测值为 5.3%，阴性预测值为 94.1%。B 组冰冻切片组织病理学诊断的敏感性为 75.0%，特异性为 96.5%，阳性预测值为 85%，阴性预测值为 95.3%。 结论: 术中冰冻切片组织病理学对髋关节翻修术前未发生脱位或假体周围骨折的 PJI 诊断是可靠的。
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.