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Background

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe.

Methods

A retrospective multi-center study including 1056 MPA patients, between 2012 and 2015, from nine centers in UK, Germany, Italy, Hungary and the Swedish registry was performed. Follow-up was at least 12 months. Cox proportional Harzards regression was used for uni- and multivariable evaluation of prognostic factors.

Results

Of 1056 MPA patients, 1030 (98.7%) were assessable for survival analysis. Gemcitabine monotherapy was the most commonly used regimen (41.3%), compared to FOLFIRINOX (n = 204, 19.3%), NAB+GEM (n = 81, 7.7%) and other gemcitabine- or 5-FU-based regimens (n = 335, 31.7%). The median overall survival (OS) was: FOLFIRINOX 9.9 months (95%CI 8.4–12.6), NAB+GEM 7.9 months (95%CI 6.2–10.0), other combinations 8.5 months (95%CI 7.7–9.3) and gemcitabine monotherapy 4.9 months (95%CI 4.4–5.6). Compared to gemcitabine monotherapy, any combination of chemotherapeutics improved the survival with no significant difference between the intensified regimens. Multivariable analysis showed an association between treatment center, male gender, inoperability at diagnosis and performance status (ECOG 1–3) with poor prognosis.

Conclusion

Gemcitabine monotherapy was predominantly used in 2012–2015. Intensified chemotherapy improved OS in comparison to gemcitabine monotherapy. In real-life settings, the OS rates of different treatment approaches are lower than shown in randomized phase III trials.  相似文献   
54.
MUC2, the major colonic mucin, forms large polymers by N-terminal trimerization and C-terminal dimerization. Although the assembly process for MUC2 is established, it is not known how MUC2 is packed in the regulated secretory granulae of the goblet cell. When the N-terminal VWD1-D2-D'D3 domains (MUC2-N) were expressed in a goblet-like cell line, the protein was stored together with full-length MUC2. By mimicking the pH and calcium conditions of the secretory pathway we analyzed purified MUC2-N by gel filtration, density gradient centrifugation, and transmission electron microscopy. At pH 7.4 the MUC2-N trimer eluted as a single peak by gel filtration. At pH 6.2 with Ca(2+) it formed large aggregates that did not enter the gel filtration column but were made visible after density gradient centrifugation. Electron microscopy studies revealed that the aggregates were composed of rings also observed in secretory granulae of colon tissue sections. The MUC2-N aggregates were dissolved by removing Ca(2+) and raising pH. After release from goblet cells, the unfolded full-length MUC2 formed stratified layers. These findings suggest a model for mucin packing in the granulae and the mechanism for mucin release, unfolding, and expansion.  相似文献   
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This article presents a treatment strategy for early release of interalveolar synechiae, aiming to facilitate early oral feeding and prevent temporomandibular joint ankylosis.The treatment results of 2 patients with van der Woude syndrome were retrospectively studied. Both patients underwent early surgical release of interalveolar synechiae under general anesthesia through fiberscopic nasal intubation. The 2 patients were treated at the ages of 6 and 14 days, respectively. The interincisival distances increased from 5 and 6 mm preoperatively to 11 and 10 mm immediately after surgery. This was increased further to 25 and 20 mm at long-term follow-up (6 and 24 months).In conclusion, synechiae between the upper and lower jaws can be safely treated at a very early age under general anesthesia with fiberscopic nasotracheal intubation. The purpose of early intervention in these cases is to facilitate oral feeding and prevent temporomandibular joint ankylosis.  相似文献   
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Abstract

Objective. This methodological study aimed to determine whether the mandibular trabecular bone assessment from panoramic radiographs, using a visual index, corresponds to the evaluation obtained from periapical radiographs. Material and methods. A panoramic radiograph and corresponding periapical radiographs of the region of the lower premolars and molars were collected from each of 32 patients (mean age 18.5 ± 5.5 years). Two calibrated observers assessed randomly the interdental sites between the first molar and second premolar and between the two premolars on all the radiographs using a visual index. Evaluations were repeated with an interval of 60 days. The results of the repeated evaluations were used to assess intra- and inter-observer agreements, employing Kappa statistics. Spearman's correlation was used to determine the association between assessments of panoramic and periapical radiographs. Results. In total, 79 interdental sites were evaluated on the panoramic and periapical radiographs. The visual analysis of periapical radiographs revealed intra-observer agreements of 0.88 for observer 1 and 0.93 for observer 2, and an inter-observer agreement of 0.82. The intra-observer agreement for panoramic radiographs was 0.79 and 0.83 for observers 1 and 2, respectively, and the inter-observer agreement was 0.79. A substantial correlation was found between periapical and panoramic radiographs (rho = 0.737, p = 0.001). Conclusions. Although panoramic radiographs are less reliable than periapical radiographs, they can be used for assessment of the trabecular bone pattern with the aid of a visual index. Training on the method is recommended to obtain results with a high reproducibility.  相似文献   
59.

Summary

The International Osteoporosis Foundation (IOF) Capture the Fracture Campaign aims to support implementation of Fracture Liaison Services (FLS) throughout the world.

Introduction

FLS have been shown to close the ubiquitous secondary fracture prevention care gap, ensuring that fragility fracture sufferers receive appropriate assessment and intervention to reduce future fracture risk.

Methods

Capture the Fracture has developed internationally endorsed standards for best practice, will facilitate change at the national level to drive adoption of FLS and increase awareness of the challenges and opportunities presented by secondary fracture prevention to key stakeholders. The Best Practice Framework (BPF) sets an international benchmark for FLS, which defines essential and aspirational elements of service delivery.

Results

The BPF has been reviewed by leading experts from many countries and subject to beta-testing to ensure that it is internationally relevant and fit-for-purpose. The BPF will also serve as a measurement tool for IOF to award ‘Capture the Fracture Best Practice Recognition’ to celebrate successful FLS worldwide and drive service development in areas of unmet need. The Capture the Fracture website will provide a suite of resources related to FLS and secondary fracture prevention, which will be updated as new materials become available. A mentoring programme will enable those in the early stages of development of FLS to learn from colleagues elsewhere that have achieved Best Practice Recognition. A grant programme is in development to aid clinical systems which require financial assistance to establish FLS in their localities.

Conclusion

Nearly half a billion people will reach retirement age during the next 20 years. IOF has developed Capture the Fracture because this is the single most important thing that can be done to directly improve patient care, of both women and men, and reduce the spiralling fracture-related care costs worldwide.  相似文献   
60.

Summary

Degenerative changes of the lumbar spine may lead to misinterpretation of bone mineral density (BMD) measurements and cause underdiagnosis of osteoporosis. This longitudinal study of 1,044 women, 75 years at inclusion and followed for 10 years, shows that identification of apparent degenerative changes on the dual energy X-ray absorptiometry (DXA) scan can increase the proportion diagnosed.

Introduction

In the elderly, degenerative manifestations in the lumbar spine may result in falsely elevated BMD values, consequently missing a large proportion of those with osteoporosis. Our aim was to determine the distribution and impact of degenerative changes on lumbar spine DXA over time and its clinical implications.

Methods

Participants were 1,044 women from the population-based Osteoporosis Risk Assessment cohort. All women were 75 years old at invitation and followed up after 5 years (n?=?715) and 10 years (n?=?382). Degenerative changes were evaluated visually on the DXA image for each vertebra L1 to L4 (intraobserver precision kappa values of 0.66–0.70).

Results

At baseline, apparent degenerative changes were more frequent in the inferior segments of the lumbar spine [5 % (L1), 15 % (L2), 26 % (L3), and 36 % (L4)] and increased over time. At 10 years, the prevalences were 20 % (L1), 39 % (L2), 59 % (L3), 72 % (L4), resulting in a significant increase in overall BMD. In women without apparent degenerative changes, BMD remained stable between 75 and 85 rather than an expected bone loss. At baseline, 37 % had osteoporosis (BMD?<??2.5) at L1–L4; exclusion of women with apparent degenerative changes increased this proportion to 47 %. Using L1–L2, which was less prone to degenerative changes, 46 % of women were classified as osteoporotic regardless of degenerative changes.

Conclusion

Degenerative changes were very common in elderly women, accelerated disproportionately over time, were increasingly frequent from vertebrae L1 to L4, and had significant impact on diagnosing osteoporosis. This suggests that routine reporting of spine BMD at L1–L2 would add valuable information for reassessment and monitoring.  相似文献   
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