Correction to: Analysis of autonomic outcomes in APOLLO,a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Journal of Neurology - The original version of this article unfortunately contained a mistake.     

Analysis of autonomic outcomes in APOLLO,a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, − 7.5; 95% CI: − 11.9, − 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, − 1.1; − 1.8, − 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; − 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, − 0.3; − 0.5, − 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, − 5.3; 95% CI: − 7.9, − 2.7) and individual domains, orthostatic intolerance (− 4.6; − 6.3, − 2.9) and gastrointestinal symptoms (− 0.8; − 1.5, − 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.

     

Evaluation of low-viscosity bulk-fill composites regarding marginal and internal adaptation

This study aimed at evaluating the marginal and internal adaptation of low-viscosity bulk-fill composites to enamel and dentin using a self-etch or an etch-and-rinse adhesive without and with artificial ageing. Hundred and twenty-eight MOD cavities in extracted molars were assigned to eight groups (n = 16), restored with the adhesives OptiBond FL (OFL) or Xeno V+ (X) and two low-viscosity bulk-fill composites SDR or x-tra base, covered with Premise. Tetric EvoCeram Bulk Fill and Premise served as a control. n = 8 per group were subjected to prolonged water storage (180 days) and thermocycling (2500×). Scanning electron microscopy was used to determine marginal gaps (MG) and interfacial adhesive defects (IAD). There were no significant differences between composite types in 44 out of 48 (MG) or 43/48 (IAD) comparisons. More MG were observed with X than with OFL (14 out of 16 comparisons, two significant), while in 16 of 16 comparisons with X more IAD were observed (14 significant). After artificial ageing, MG generally increased (9/16 significant), compared to IAD (one significant). The performance of the investigated composite types concerning the integrity of the tooth-composites interface was comparable. Compared to the 1-step self-etch system, the bond with the 3-step etch-and-rinse adhesive was raised.

     

Comparison of volumetric bone mineral density in the operated and contralateral knee after anterior cruciate ligament and reconstruction: A 1‐year follow‐up study using peripheral quantitative computed tomography

The purpose of this study was to quantify changes in volumetric bone mineral density (vBMD) in the tibial plateau of the operated and contralateral leg measured using peripheral quantitative computed tomography (pQCT) before and 3, 6, and 12 months after anterior cruciate ligament (ACL) reconstruction. The ACL was reconstructed with a hamstring tendon autograft using press‐fit fixation. pQCT measurements of the proximal tibia were obtained in 61 patients after ACL reconstruction, and total, cortical, and trabecular vBMD were calculated. vBMD in the operated leg decreased from baseline to 3 months (?12% [total], ?11% [cortical], and ?12.6% [trabecular]; p < 0.001) and remained below baseline for 12 months after surgery (6 months: ?9.5%, ?9.4%, and ?9.6%, p < 0.001; 12 months: ?8%, ?5%, and ?11%, p < 0.001). vBMD in the contralateral leg was slightly reduced only 6 months after surgery. Including age and sex as covariates into the analysis did not affect the results. ACL reconstruction contributed to loss in bone mineral density within the first year after surgery. The role of factors such as time of weight‐bearing, joint mechanics, post‐traumatic inflammatory reactions, or genetic predisposition in modulating the development of posttraumatic knee osteoarthritis after ACL injury should be further elucidated. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1804–1810, 2015.

     

Prognostic factors for adenoid cystic carcinoma of the head and neck: a retrospective evaluation of 96 cases

Cases of adenoid cystic carcinomas of the salivary (n = 90) and lacrimal glands (n = 6) from the years 1965-1980 were evaluated retrospectively with regard to clinical, epidemiologic and histomorphologic parameters, and in 52 cases, nuclear DNA content was assessed using a single cell scanning cytophotometry procedure in order to determine prognostic factors. Clinical courses were poor with a high incidence of recurrences, hematogenous metastases and deaths from tumor. Histology was related to prognosis, glandular tumors showing a better prognosis than solid ones. Tumor size greater than 4 cm was correlated with an unfavorable clinical course in all cases. Cytophotometry yielded various types of histograms (7 diploid, 10 proliferative, 14 triploid, 19 atypical, 2 tetraploid). Significant correlations were found as to the time of survival, tumors with diploid histograms showing the longest intervals and those with atypical ones the shortest. Although the prognosis of adenoid cystic carcinoma remains poor, cytophotometry can offer additional prognostic information in the individual case.     

Sonography of the temporomandibular joint from 60 examinations and comparison with MRI and axiography

BACKGROUND AND OBJECTIVE: Establishing a diagnosis of temporomandibular joint disorder is mainly based on clinical assessment, functional examination, nuclear magnetic resonance imaging (MRI) and axiography. Sonographic examination was compared with MRI and axiography in assessing temporomandibular joint (TMJ) function in 55 patients. PATIENTS AND METHODS: Fifty-five patients with different TMJ problems were examined clinically, by means of axiography, sonography and some also by MRI. The range of motion was measured by sonography and axiography and the results compared using Student's t-test. Anatomical details diagnostic for disc-displacement were tested by sonography and MRI. RESULTS: The average time required for sonography was 2 min and for axiography 20 min. The mean measurement differences for condylar movement in maximal mouth opening was 1.7 mm, for protrusion 1.6 mm and for mediotrusion 2.5 mm. The range of condylar movement as measured by sonography and axiography coincided for opening and for protrusion (statistically significant). No significance was found for lateral excursions. The concordance in diagnosis of disc dislocation, hypermobility and impaired range of motion when comparing ultrasound with MRI was 83%. All sonographic examinations were performed by one person only. Sixty repeat examinations in patients produced no complaints and showed an absolute range of difference of 0.6 mm, with a relative range of 7%. Student's t-test was significant (p<0.05) (two repetitive measurements). CONCLUSION: Sonography proved to be a fast and reliable method for evaluating the range of movement of the TMJ. The lateral joint capsule, lateral disc, and upper condyle could be demonstrated. Pathological processes such as anterior or lateral disc displacement, disc perforation, seroma following contusion, capsular fibrosis, crystalline structures in the synovia and fracture dislocation of the condyle could be diagnosed with considerable reliability when compared with MRI. However, the medial aspect of the joint, medial disc dislocation and the angulation of the condylar slope could not be seen.     

无机抗菌剂对自酸蚀处理剂全身毒性和细胞毒性影响的研究

目的测试无机抗菌剂的添加对新型实验自酸蚀处理剂（ESP）全身毒性和细胞毒性的影响。方法将6种无机抗菌剂分别加入ESP中，进行经口途径大鼠短期全身毒性实验。并采用受试材料与NIH3T3细胞直接接触培养的方法，观测其对细胞增殖、活力和形态的影响。结果抗菌剂添加比为5.0%时，为期2周的大鼠全身毒性实验中未发现临床毒性体征，各组间大鼠体重相对增长率无显著差异。经含质量浓度为0.5%不同抗菌剂的处理剂处理固化后的各实验组细胞活力比率和细胞增殖率与ESP空白对照组相比无显著差异。仅样本覆盖区及样本边缘邻近区域细胞可观察到毒性表现，远离样本覆盖区的细胞密度未受明显影响。结论以适当的质量浓度添加受试的无机抗菌剂对受试ESP的全身毒性和细胞毒性无显著影响。     

Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies

Journal of Clinical Immunology - Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable...