Effect of Raloxifene Treatment on Osteocyte Apoptosis in Postmenopausal Women

Increased osteocyte apoptosis, as the result of estrogen deficiency, could play a role in the decrease of bone mass and bone strength seen in postmenopausal osteoporosis. We investigated whether treatment with raloxifene of postmenopausal women with osteoporosis affects osteocyte apoptosis. Transiliac bone biopsies were obtained from 26 osteoporotic women at baseline and after 2 years of treatment with placebo or raloxifene. Immunohistochemical detection of cleaved caspase-3 was performed on sections from nondecalcified bone biopsies to visualize apoptosis. In the trabecular bone total osteocytes, positively stained osteocytes and empty lacunae were counted and percent positive cells and percent empty lacunae determined. Statistical evaluation was performed by Wilcoxon’s paired t-test and Spearman’s rank correlations. There was no significant difference in percentage positive osteocytes between baseline and follow-up biopsies in both the placebo and the raloxifene groups. The percentage empty lacunae increased significantly in the placebo group (11.20 ± 1.43 vs. 9.00 ± 2.25, P = 0.014) but not in the raloxifene group. At baseline in both groups combined, there was a negative correlation between indices of bone remodeling and the percentage positive osteocytes (bone formation rate/bone volume r = −0.67, P = 0.001). We found no direct evidence for an effect of raloxifene treatment on osteocyte apoptosis, but small effects of raloxifene treatment cannot be excluded. The percent of apoptotic osteocytes was dependent on the level of bone remodeling in an individual

Have Surgery and Implant Modifications Been Associated With Reduction in Soft Tissue Complications in Transfemoral Bone-anchored Prostheses?

BackgroundThe most frequently occurring adverse events in individuals with a transfemoral amputation treated with a bone-anchored prosthesis are soft tissue infections and stoma-related complications. These soft tissue complications are believed to be influenced by surgical technique and implant design, but little is known about the effect of changes to treatment on these events.Questions/purposes(1) What is the result of surgical technique and implant modifications on the incidence of soft tissue infections and stoma-related complications in transfemoral bone-anchored prosthesis users, depending on whether they had a conventional stoma and a cobalt-chrome-molybdenum (CoCrMo) osseointegration implant (treatment period 2009 to 2013) or a shallower stoma and titanium osseointegration implant (2015 to 2018)? (2) What is the incidence of serious complications, such as bone or implant infection, aseptic loosening, intramedullary stem breakage, and periprosthetic fracture?MethodsBetween 2009 and 2013, we performed osseointegration implant surgery using a conventional surgical technique and a CoCrMo implant in 42 individuals who had a lower extremity amputation experiencing socket-related problems that resulted in limited prosthesis use. We considered all individuals treated with two-stage surgery with a standard press-fit transfemoral osseointegration implant as potentially eligible for inclusion. Based on this, 100% (42) were eligible, and 5% (two of 42) were excluded because they did not provide informed consent, leaving 95% (40 of 42) for analysis. Between 2015 and 2018, we treated 79 individuals with similar indications with osseointegration implant surgery, now also treating individuals with dysvascular amputations. We used an adapted surgical technique resulting in a shallower stoma combined with a titanium implant. Using the same eligibility criteria as for the first group, 51% (40 of 79) were eligible; 49% (39 of 79) were excluded because they were treated with transtibial amputation, a patient-specific implant, or single-stage surgery and 1% (one of 79) were lost before the 2-year follow-up interval, leaving 49% (39 of 79) for analysis. The period of 2013 to 2015 was a transitional period and was excluded from analysis in this study to keep groups reasonably comparable and to compare a historical approach with the present approach. Hence, we presented a comparative study of two study groups (defined by surgical technique and implant design) with standardized 2-year follow-up. The risk factors for adverse events were similar between groups, although individuals treated with the shallow stoma surgical technique and titanium implant potentially possessed an increased risk because of the inclusion of individuals with dysvascular amputation and the discontinuation of prolonged postoperative antibiotic prophylaxis. Outcomes studied were soft tissue infections and stoma-related complications (hypergranulation or keloid formation as well as stoma redundant tissue) and bone or implant infection, aseptic loosening, implant stem breakage, periprosthetic fracture, and death.ResultsPatients treated with the shallow stoma surgical technique and titanium implant experienced fewer soft tissue infections (13 versus 76 events, absolute risk 0.17 [95% CI 0.09 to 0.30] versus 0.93 [95% CI 0.60 to 1.45]; p &lt; 0.01), which were treated with less invasive measures, and fewer stoma redundant tissue events (0 versus five events, absolute risk 0 versus 0.06 [95% CI 0.03 to 0.14]) than patients treated with the conventional stoma surgical technique and CoCrMo implant. This was contrasted by an increased incidence of surgical site infections occurring between surgical stages 1 and 2, when no stoma was yet created, after the implementation of treatment changes (conventional surgery and CoCrMo implant versus shallow stoma surgery and titanium implant: one versus 11 events, absolute risk 0.01 [95% CI 0.00 to 0.08] versus 0.14 [95% CI 0.08 to 0.25]; p = 0.02). Patients treated with the shallow stoma surgical technique and titanium implant did not experience serious complications, although bone infections occurred (six events in 8% [three of 40] of patients) in the conventional surgery and CoCrMo implant group, all of which were successfully treated with implant retention.ConclusionAdaptations to surgical technique and newer implant designs, as well as learning curve and experience, have resulted in a reduced incidence and severity of soft tissue infections and stoma redundant tissue, contrasted by an increase in surgical site infections before stoma creation. Serious complications such as deep implant infection were infrequent in this 2-year follow-up period. We believe the benefits of these treatment modifications outweigh the disadvantages and currently advise surgeons to create a shallower stoma with a stable soft tissue envelope, combined with a titanium implant.Level of EvidenceLevel III, therapeutic study.</p

Fatal Hemothorax Caused by Pseudomesotheliomatous Carcinoma of the Lung

We present a case of a poorly differentiated pseudomesotheliomatous carcinoma originating in the lung, which was manifested with the distinctly rare complication of massive true hemothorax and persistent blood loss that proved rapidly fatal in spite of surgery. Pseudomesotheliomatous carcinoma of the lung and neoplasia-associated hemothorax are reviewed and discussed

Directional Sinogram Inpainting for Limited Angle Tomography

In this paper we propose a new joint model for the reconstruction of tomography data under limited angle sampling regimes. In many applications of Tomography, e.g. Electron Microscopy and Mammography, physical limitations on acquisition lead to regions of data which cannot be sampled. Depending on the severity of the restriction, reconstructions can contain severe, characteristic, artefacts. Our model aims to address these artefacts by inpainting the missing data simultaneously with the reconstruction. Numerically, this problem naturally evolves to require the minimisation of a non-convex and non-smooth functional so we review recent work in this topic and extend results to fit an alternating (block) descent framework. \oldtext{We illustrate the effectiveness of this approach with numerical experiments on two synthetic datasets and one Electron Microscopy dataset.} \newtext{We perform numerical experiments on two synthetic datasets and one Electron Microscopy dataset. Our results show consistently that the joint inpainting and reconstruction framework can recover cleaner and more accurate structural information than the current state of the art methods

Recent Progress and Recommendations on Celiac Disease From the Working Group on Prolamin Analysis and Toxicity

Celiac disease (CD) affects a growing number of individuals worldwide. To elucidate the causes for this increase, future multidisciplinary collaboration is key to understanding the interactions between immunoreactive components in gluten-containing cereals and the human gastrointestinal tract and immune system and to devise strategies for CD prevention and treatment beyond the gluten-free diet. During the last meetings, the Working Group on Prolamin Analysis and Toxicity (Prolamin Working Group, PWG) discussed recent progress in the field together with key stakeholders from celiac disease societies, academia, industry and regulatory bodies. Based on the current state of knowledge, this perspective from the PWG members provides recommendations regarding clinical, analytical and legal aspects of CD. The selected key topics that require future multidisciplinary collaborative efforts in the clinical field are to collect robust data on the increasing prevalence of CD, to evaluate what is special about gluten-specific T cells, to study their kinetics and transcriptomics and to put some attention to the identification of the environmental agents that facilitate the breaking of tolerance to gluten. In the field of gluten analysis, the key topics are the precise assessment of gluten immunoreactive components in wheat, rye and barley to understand how these are affected by genetic and environmental factors, the comparison of different methods for compliance monitoring of gluten-free products and the development of improved reference materials for gluten analysis

Predictive factors for sustained pain after (sub)acute osteoporotic vertebral fractures:Combined results from the VERTOS II and VERTOS IV trial

PURPOSE: Osteoporotic vertebral compression fractures are treated conservatively or in selected cases with percutaneous vertebroplasty (PV). The purpose of this retrospective analysis is to determine predictive factors for a high visual analogue scale (VAS) pain score after conservative, sham or PV and is based on previously published randomized trials. METHODS: The VERTOS II compared conservative versus PV, and VERTOS IV compared sham versus PV treatment. The conservative group received pain medication. The sham and PV group received subcutaneous lidocaine/bupivacaine. In addition, the PV group received cementation, which was simulated in the sham group. Nineteen different predictors of high (≥ 5) versus low ( 8, long-term baseline pain, mild/severe Genant and new fractures. CONCLUSIONS: Statistically significant more patients had a high pain score at 12 months in the sham and conservative group when compared with the PV group. Five predictors were identified for sustained high local back pain, regardless of the received treatment. Patients with moderate fracture deformity were less likely to have high pain scores at 12 months if they received PV than if they had sham or conservative therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00270-022-03170-7

Health economic evaluation of nation-wide screening programmes for atrial fibrillation in the Netherlands

AIMS: Screening for atrial fibrillation (AF) is recommended by the European Society of Cardiology guideline to prevent strokes. Cost-effectiveness analyses of different screening programs for AF are difficult to compare, because of varying settings and models used. We compared the impact and cost-effectiveness of various AF screening programs in the Netherlands.METHODS AND RESULTS: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the ARISTOTLE, RE-LY and ROCKET AF trial combined with Dutch observational data. Univariate, probabilistic sensitivity and various scenario analyses were performed. The maximum number of newly detected AF patients in The Netherlands ranged from 4554 to 39 270, depending on the screening strategy used. Adequate treatment with anticoagulation would result in a maximum of more than 3000 strokes prevented using single time point AF screening. Compared with no screening, screening 100 000 persons provided a gain in QALYs ranging from 984 to 8727, and a mean cost difference ranging from -6650 000€ to 898 000€, depending on the screening strategy used. Probabilistic sensitivity analysis (PSA) demonstrated a 100% likelihood that screening all patients ≥ 75 years visiting the Geriatric outpatient clinic was cost-saving. Four out of six strategies were cost-saving in ≥ 74% of the PSA simulations. Out of these, opportunistic screening of all patients ≥ 65 years visiting the GPs office had the highest impact on strokes prevented.CONCLUSION: Most single-time point AF screening strategies are cost-saving and have an important impact on stroke prevention.</p

Health economic evaluation of nation-wide screening programmes for atrial fibrillation in the Netherlands

AIMS: Screening for atrial fibrillation (AF) is recommended by the European Society of Cardiology guideline to prevent strokes. Cost-effectiveness analyses of different screening programs for AF are difficult to compare, because of varying settings and models used. We compared the impact and cost-effectiveness of various AF screening programs in the Netherlands.METHODS AND RESULTS: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the ARISTOTLE, RE-LY and ROCKET AF trial combined with Dutch observational data. Univariate, probabilistic sensitivity and various scenario analyses were performed. The maximum number of newly detected AF patients in The Netherlands ranged from 4554 to 39 270, depending on the screening strategy used. Adequate treatment with anticoagulation would result in a maximum of more than 3000 strokes prevented using single time point AF screening. Compared with no screening, screening 100 000 persons provided a gain in QALYs ranging from 984 to 8727, and a mean cost difference ranging from -6650 000€ to 898 000€, depending on the screening strategy used. Probabilistic sensitivity analysis (PSA) demonstrated a 100% likelihood that screening all patients ≥ 75 years visiting the Geriatric outpatient clinic was cost-saving. Four out of six strategies were cost-saving in ≥ 74% of the PSA simulations. Out of these, opportunistic screening of all patients ≥ 65 years visiting the GPs office had the highest impact on strokes prevented.CONCLUSION: Most single-time point AF screening strategies are cost-saving and have an important impact on stroke prevention.</p

Health economic evaluation of nation-wide screening programmes for atrial fibrillation in the Netherlands

AIMS: Screening for atrial fibrillation (AF) is recommended by the European Society of Cardiology guideline to prevent strokes. Cost-effectiveness analyses of different screening programs for AF are difficult to compare, because of varying settings and models used. We compared the impact and cost-effectiveness of various AF screening programs in the Netherlands.METHODS AND RESULTS: The base case economic analysis was conducted from the societal perspective. Health effects and costs were analysed using a Markov model. The main model inputs were derived from the ARISTOTLE, RE-LY and ROCKET AF trial combined with Dutch observational data. Univariate, probabilistic sensitivity and various scenario analyses were performed. The maximum number of newly detected AF patients in The Netherlands ranged from 4554 to 39 270, depending on the screening strategy used. Adequate treatment with anticoagulation would result in a maximum of more than 3000 strokes prevented using single time point AF screening. Compared with no screening, screening 100 000 persons provided a gain in QALYs ranging from 984 to 8727, and a mean cost difference ranging from -6650 000€ to 898 000€, depending on the screening strategy used. Probabilistic sensitivity analysis (PSA) demonstrated a 100% likelihood that screening all patients ≥ 75 years visiting the Geriatric outpatient clinic was cost-saving. Four out of six strategies were cost-saving in ≥ 74% of the PSA simulations. Out of these, opportunistic screening of all patients ≥ 65 years visiting the GPs office had the highest impact on strokes prevented.CONCLUSION: Most single-time point AF screening strategies are cost-saving and have an important impact on stroke prevention.</p