Primary vaccination in adult patients after allogeneic hematopoietic stem cell transplantation – A single center retrospective efficacy analysis

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6–70.6 years). All patients with a relapse-free survival of ≥9 months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3 months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients’ characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n = 75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n = 9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p < 0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p = 0.026; mean IgG of responders 816 mg/dl vs. 475 mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p = 0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.     

基于SEER数据库脊索瘤临床预测模型的建立及验证

目的构建脊索瘤患者的预测模型并进行验证。方法从SEER数据库(2004~2015年)中鉴定和收集597例脊索瘤患者。Nomogram是基于建模组420例拥有完整数据的患者建立的。C指数(C-index)和校正曲线确定Nomogram的预测精度和判别能力。结果建立了基于年龄、种族、原发部位及数量、肿瘤分期(TNM)、手术方式、是否放疗、肿瘤转移和肿瘤大小等预后因素的预测模型,C指数为0.778。确定生存概率的校准曲线表明,Nomogram预测结果与实际观测结果吻合较好。年龄>60岁(P<0.001,HR 5.723,95%CI 1.988~16.474)、M1(P<0.001,HR 4.121,95%CI 1.834~9.257)、手术方式(全切除,P<0.01,HR0.416,95%CI 0.236~0.732;根治性扩大切除,P<0.0001,HR 0.251,95%CI 0.143~0.442)是独立预后因素。结论 Nomogram为脊柱脊索瘤患者提供了更准确的预后预测。本研究结果显示,年龄>60岁肿瘤分期M1和不进行手术是显著缩短脊索瘤患者生存时间的独立危险因素。     

A guide to assessing post-operative complications following en bloc spinal resection

En-bloc resection of spinal tumours is a complex procedure with significant morbidity and mortality. The extensive resection leaves a large soft tissue and osseous defect requiring reconstruction. Following en-bloc resection, there may be complications relating to both the removal of the tumour and the subsequent reconstruction. This paper outlines the imaging appearances of the frequently encountered complications in our experience. The primary aim is to improve the confidence of the radiologist when reporting imaging following spinal en-bloc resection, however we believe this is also useful for the spinal and orthopaedic surgeons in assessing the patients following en block resection.     

液晶数字显示角度仪在全髋关节置换术中的应用价值

目的:探讨在全髋关节置换术中使用液晶数字显示角度仪控制前倾角的应用价值。方法:回顾分析自2018年1月至2019年12月83例行初次全髋关节置换术的患者,其中男28例,女55例;年龄42~81(70.4±7.9)岁。股骨颈骨折63例,股骨头缺血性坏死20例。所有患者术中使用液晶数显角度仪控制髋臼杯假体的前倾角,术后采用CT扫描,测量髋臼杯的前倾角,两者进行比较,了解使用液晶数显角度仪的准确性。结果:术后CT测量提示患者的髋臼前倾角均位于Lewinnek提倡的安全区内,术中使用液晶数显角度仪测量髋臼杯的前倾角度中位数为14.20°(12.80~15.40)°,术后CT扫描测量的髋臼杯的前倾角中位数为14.20°(13.40~15.50)°,两者比较差异无统计学意义(Z=-1.725,P=0.085)。结论:应用液晶数显角仪器对术中控制髋臼杯的前倾角是一种准确可靠的方法,具有良好的辅助参考价值。     

Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?

Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured.ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation.ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients.     

Instability of the extensor digitorum tendons in Jaccoud arthropathy assessed by semi-dynamic MRI of the metacarpophalangeal joints

PurposeThe purpose of this study was to test the hypothesis that Jaccoud arthropathy (JA) in patients with systemic lupus erythematosus (SLE) is associated with instability of the extensor digitorum (ED) tendons during flexion of the metacarpophalangeal (MCP) joints by comparing the position of the ED tendons between SLE patients with JA and control subjects on hand MRI obtained with flexed and extended MCP joints.Materials and methodsThirty-two hands of SLE patients with JA (13 women and 3 men; mean age, 50.0 ± 12.2 [SD] years; age range: 26–68 years) and 24 hands of sex- and age-matched control subjects (20 women and 4 men; mean age, 50.1 ± 13.0 [SD] years; age range: 24–68 years) were included in the study. Axial spin echo T1-weighted MRI images of the second to fifth MCP joints in flexion and in extension were obtained. Two radiologists (R1 and R2) separately measured the amplitude and assessed the direction of the displacement of the ED tendons with respect to the midline at the level of each MCP joint. Statistical analysis included two-way ANOVA with random effects to assess differences in amplitude and Fisher–Freeman–Halton exact test to assess differences in direction with P-values < 0.0083 and < 0.0063 considered as statistically significant respectively.ResultsAmplitude of the displacement of the ED tendons was statistically significantly greater in SLE patients with JA than in control subjects in flexion for both readers (median 58°, 95% confidence interval [CI]: 50°–65° vs. 20°, 95% CI: 16°–24°; P < 0.0001 for R1 and 54°, 95% CI: 47°–61° vs. 25°, 95% CI: 22°–28°; P < 0.0001 for R2) and in extension for one reader (17°, 95% CI: 15°–20° vs. 14°, 95% CI: 11°–16°; P = 0.0048 for R1 and 20°, 95% CI: 15°–25° vs. 16°, 95% CI: 12°–18°; P = 0.0292 for R2). Ulnar deviation of the ED tendons was statistically significantly more frequent in SLE patients with JA than in control subjects in flexion and in extension for both readers (P < 0.0001).ConclusionJA is associated with instability of the ED tendons in patients with SLE best depicted when MCP joints are flexed.     

Vasovagal reactions after COVID-19 vaccination in Japan

Coronavirus disease 2019 (COVID-19) vaccine administration started in February 2021 in Japan. As of December 2021, approximately 75% of the population aged ≥12 years had received two doses of vaccine. We conducted a study to investigate vasovagal reactions (VVR) after COVID-19 vaccination using data on adverse events following immunization. The crude reporting rate of VVR (cases/1,000,000 doses) after vaccination was 9.6 in all age groups combined, and was more frequent in the younger age groups: 28.6 and 37.2 in individuals aged 10–19 years and 20–29 years, respectively. In individuals aged 10–29 years, the rate was similar in males and females (33.0 and 34.2, respectively, p = 0.53); but was higher after dose 1 than after dose 2 (57.4 and 8.8, respectively, p < 0.001). Based on these results, caution needs to be exercised when vaccinating adolescents and young adults, especially with dose 1 of COVID-19 vaccines.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.