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91.

Objective

Osteolysis has not been recognized as a common failure mode of the Birmingham modular metal-on-metal (MoM) total hip arthroplasty (THA). The clinical value of metal artifact reduction sequence (MARS) magnetic resonance imaging (MRI) to assess the periprosthetic soft tissue is well documented; however, the appropriate image modalities to detect periacetabular osteolysis remain unclear.

Case summary

Eleven patients with periacetabular osteolysis within 3–6 years after uncemented Birmingham modular MoM THA with a synergy stem are presented. All 11 patients received corresponding standardized AP pelvis radiographs, high-quality MARS MRIs and CT scans with a metal artifact reduction sequence. While periacetabular osteolysis around MoM THA was not detected on MARS MRI in ten patients, CT imaging identified osteolysis in all patients. Periacetabular osteolysis appears to be a failure mechanism of the Smith & Nephew Birmingham MoM THA.

Discussion

There is no evidence in the literature to support the effectiveness of MARS MRI to detect periacetabular osteolysis around cobalt chromium alloy metal-on-metal total hip arthroplasties. Osteolysis due to corrosion-related particles seems to be one of the primary modes of failure in modular MoM THA.

Conclusions

MRI is not a sensitive test to identify periacetabular osteolysis. The authors recommend CT for the screening of implants with this failure mode. Our study suggests that patients with a Birmingham modular MoM THA are at increased risk to develop acetabular osteolysis and should be carefully monitored for this failure mode.  相似文献   
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MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.  相似文献   
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Background: We aimed to determine the concordance between the radiologic stage (rT), using multiparametric magnetic resonance imaging (mpMRI), and pathologic stage (pT) in patients with high-risk prostate cancer and its influence on nerve-sparing surgery compared to the use of the intraoperative frozen section technique (IFST). Methods: The concordance between rT and pT and the rates of nerve-sparing surgery and positive surgical margin were assessed for patients with high-risk prostate cancer who underwent radical prostatectomy. Results: The concordance between the rT and pT stages was shown in 66.4% (n = 77) of patients with clinical high-risk prostate cancer. The detection of patients with extraprostatic disease (≥pT3) by preoperative mpMRI showed a sensitivity, negative predictive value and accuracy of 65.1%, 51.7% and 67.5%. In addition to the suspicion of extraprostatic disease in mpMRI (≥rT3), 84.5% (n = 56) of patients with ≥rT3 underwent primary nerve-sparing surgery with IFST, resulting in 94.7% (n = 54) of men with at least unilateral nerve-sparing surgery after secondary resection with a positive surgical margin rate related to an IFST of 1.8% (n = 1). Conclusion: Patients with rT3 should not be immediately excluded from nerve-sparing surgery, as by using IFST some of these patients can safely undergo nerve-sparing surgery.  相似文献   
95.
目的:探讨孟鲁司特钠联合硫酸镁治疗老年支气管哮喘的临床疗效。方法选取2012年6月至2013年6月玉林市第二人民医院收治的老年支气管哮喘患者80例,按照随机数字表法分为观察组与对照组各40例。对照组给予吸氧、抗感染、祛痰、β2受体激动剂、糖皮质激素等常规治疗,观察组在对照组的基础上加用孟鲁司特钠片和硫酸镁注射液治疗。观察并比较两组的临床疗效。结果观察组总有效率为97.1%明显高于对照组的77.1%,复发率为5.7%明显低于对照组的28.6%,差异均有统计学意义( P<0.05);观察组喘息、咳嗽及胸闷等症状缓解时间均明显早于对照组,差异有统计学意义(P<0.05)。两组患者治疗前肺功能指标比较,差异无统计学意义(P>0.05);治疗后肺功能指标较治疗前均明显改善,观察组改善程度优于对照组,差异有统计学意义(P<0.05)。两组均未见呼吸抑制、血压下降等严重不良反应。结论孟鲁司特钠片联合硫酸镁注射液治疗老年支气管哮喘临床疗效显著,症状缓解快,复发率低,安全可靠,值得临床推广。  相似文献   
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Chronic neutrophilic leukemia (CNL) relates to mutational CSF3R activation with membrane proximal CSF3R mutations such as T618I as driver mutations, but the significance of truncating mutations is not clarified. In CNL, concomitant mutations promote disease progression, but insight into longitudinal acquisition is incomplete. In this study, we investigated the role of co-occurring germline and somatic CSF3R mutations in CNL, and assessed the impact of clonal evolution on transformation to acute leukemia. We employed sequential next generation sequencing and SNP array karyotyping to assess clonal evolution in CNL of early manifestation age based on a 33-year-old patient. Germline vs. somatic mutations were differentiated using a sample from the hair follicle. To investigate a potential predisposition for CNL development and progression by germline CSF3R-W791*, allelic localizations were evaluated. We detected a somatic CSF3R-T618I mutation at 46% variant allele frequency (VAF) at the time of CNL diagnosis, which co-occurred with a CSF3R-W791* truncation at 50% VAF in the germline. Evaluation of allelic localization revealed CSF3R-T618I and W791* on the same allele. A concomitant ASXL1 mutation at 39% VAF increased to 48% VAF upon transformation to mixed phenotype acute leukemia (MPAL), which has both myeloid and lymphoid features. Clonal evolution further involved expansion of the CSF3R double-mutant clone to 90% VAF via copy neutral loss of heterozygosity on chromosome 1p and the emergence of a RUNX1 mutant subclone. Allogeneic transplantation induced complete remission. This study highlights that CNL not only transforms to AML but also to MPAL. The molecular evolution is especially interesting with a CSF3R-W791* mutation in the germline and acquisition of CSF3R-T618I on the same allele compatible with increased susceptibility for mutation acquisition facilitating RUNX1-related clonal transformation.  相似文献   
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