Anti-pruritic effect of nemolizumab in hemodialysis patients with uremic pruritus: a phase II,randomized, double-blind,placebo-controlled clinical study

Clinical and Experimental Nephrology - The pathophysiology of uremic pruritus (UP), which is characterized by systemic and intractable itching, remains unclear. As interleukin (IL)-31 may be...     

Lumbar degenerative spondylolisthesis: factors associated with the decision to fuse

BACKGROUND CONTEXTThe indication to perform a fusion and decompression surgery as opposed to decompression alone for lumbar degenerative spondylolisthesis (LDS) remains controversial. A variety of factors are considered when deciding on whether to fuse, including patient demographics, radiographic parameters, and symptom presentation. Likely surgeon preference has an important influence as well.PURPOSEThe aim of this study was to assess factors associated with the decision of a Canadian academic spine surgeon to perform a fusion for LDS.STUDY DESIGN/SETTINGThis study is a retrospective analysis of patients prospectively enrolled in a multicenter Canadian study that was designed to evaluate the assessment and surgical management of LDS.PATIENT SAMPLEInclusion criteria were patients with: radiographic evidence of LDS and neurogenic claudication or radicular pain, undergoing posterior decompression alone or posterior decompression and fusion, performed in one of seven, participating academic centers from 2015 to 2019.OUTCOME MEASURESPatient demographics, patient-rated outcome measures (Oswestry Disability Index [ODI], numberical rating scale back pain and leg pain, SF-12), and imaging parameters were recorded in the Canadian Spine Outcomes Research Network (CSORN) database. Surgeon factors were retrieved by survey of each participating surgeon and then linked to their specific patients within the database.METHODSUnivariate analysis was used to compare patient characteristics, imaging measures, and surgeon variables between those that had a fusion and those that had decompression alone. Multivariate backward logistic regression was used to identify the best combination of factors associated with the decision to perform a fusion.RESULTSThis study includes 241 consecutively enrolled patients receiving surgery from 11 surgeons at 7 sites. Patients that had a fusion were younger (65.3±8.3 vs. 68.6±9.7 years, p=.012), had worse ODI scores (45.9±14.7 vs. 40.2±13.5, p=.007), a smaller average disc height (6.1±2.7 vs. 8.0±7.3 mm, p=.005), were more likely to have grade II spondylolisthesis (31% vs. 14%, p=.008), facet distraction (34% vs. 60%, p=.034), and a nonlordotic disc angle (26% vs. 17%, p=.038). The rate of fusion varied by individual surgeon and practice location (p<.001, respectively). Surgeons that were fellowship trained in Canada more frequently fused than those who fellowship trained outside of Canada (76% vs. 57%, p=.027). Surgeons on salary fused more frequently than surgeons remunerated by fee-for-service (80% vs. 64%, p=.004). In the multivariate analysis the clinical factors associated with an increased odds of fusion were decreasing age, decreasing disc height, and increasing ODI score; the radiographic factors were grade II spondylolisthesis and neutral or kyphotic standing disc type; and the surgeon factors were fellowship location, renumeration type and practice region. The odds of having a fusion surgery was more than two times greater for patients with a grade II spondylolisthesis or neutral and/or kyphotic standing disc type (opposed to lordotic standing disc type). Patients whose surgeon completed their fellowship in Canada, or whose surgeon was salaried (opposed to fee-for-service), or whose surgeon practiced in western Canada had twice the odds of having fusion surgery.CONCLUSIONSThe decision to perform a fusion in addition to decompression for LDS is multifactorial. Although patient and radiographic parameters are important in the decision-making process, multiple surgeon factors are associated with the preference of a Canadian spine surgeon to perform a fusion for LDS. Future work is necessary to decrease treatment variability between surgeons and help facilitate the implementation of evidence-based decision making.     

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

A surveillance study of patterns of reirradiation practice using external beam radiotherapy in Japan

The aim of this study was to survey the present status and patterns of reirradiation (Re-RT) practice using external beam radiotherapy in Japan. We distributed an e-mail questionnaire to the Japanese Society for Radiation Oncology partner institutions, which consisted of part 1 (number of Re-RT cases in 2008–2012 and 2013–2018) and part 2 (indications and treatment planning for Re-RT and eight case scenarios). Of the 85 institutions that replied to part 1, 75 (88%) performed Re-RTs. However, 59 of these 75 institutions (79%) reported difficulty in obtaining Re-RT case information from their databases. The responses from 37 institutions included the number of Re-RT cases, which totaled 508 in the period from 2009 to 2013 (institution median 3; 0–235), and an increase to 762 cases in the period from 2014 to 2018 (12.5; 0–295). A total of 47 physicians responded to part 2 of the survey. Important indications for Re-RT that were considered were age, performance status, life expectancy, absence of distant metastases and time interval since previous radiotherapy. In addition to clinical decision-making factors, previous total radiation dose, volume of irradiated tissue and the biologically equivalent dose were considered during Re-RT planning. From the eight site-specific scenarios presented to the respondents, >60% of radiation oncologists agreed to perform Re-RT. Re-RT cases have increased in number, and interest in Re-RT among radiation oncologists has increased recently due to advances in technology. However, several problems exist that emphasize the need for consensus building and the establishment of guidelines for practice and prospective evaluation.     

A cost-minimization analysis of measures against metallic dental restorations for head and neck radiotherapy

The aim of this study was to compare the estimated public medical care cost of measures to address metallic dental restorations (MDRs) for head and neck radiotherapy using high-energy mega-voltage X-rays. This was considered a first step to clarify which MDR measure was more cost-effective. We estimated the medical care cost of radiotherapy for two representative MDR measures: (i) with MDR removal or (ii) without MDR removal (non-MDR removal) using magnetic resonance imaging and a spacer. A total of 5520 patients received head and neck radiation therapy in 2018. The mean number of MDRs per person was 4.1 dental crowns and 1.3 dental bridges. The mean cost per person was estimated to be 121 720 yen for MDR removal and 54 940 yen for non-MDR removal. Therefore, the difference in total public medical care cost between MDR removal and non-MDR removal was estimated to be 303 268 800 yen. Our results suggested that non-MDR removal would be more cost-effective than MDR removal for head and neck radiotherapy. In the future, a national survey and cost-effectiveness analysis via a multicenter study are necessary; these investigations should include various outcomes such as the rate of local control, status of oral mucositis, frequency of hospital visits and efforts of the medical professionals.     

Changes in circulating blood volume following isoflurane or sevoflurane anesthesia

Changes of circulating blood volume (CB volume) measured by the dual indicator dilution method were observed in 33 chronically instrumented mongrel dogs following either alpha-chloralose-urethane (C group), additive isoflurane (I group) or sevoflurane anesthesia (S group). These anesthetic groups were each divided into two subgroups with regard to respiratory care, namely Cp, Ip and Sp for those with intermittent positive pressure ventilation (six animals per subgroups), and Cs, Is and Ss for those with spontaneous breathing (five animals per subgroups).The CB volume under positive pressure ventilation remained unchanged in the Ip and Sp groups at both 0.5 and 1.0 MAC, and in the Cp group. The CB volume remained essentially unchanged in the Cs and Is groups at both 0.5 or 1.0 MAC, but the plasma volume tended to increase slightly in the Is group at 1.0 MAC.In the Ss group under spontaneous breathing, however, the CB volume increased from 84.4 ± 7.0 to 91.4 ± 7.7 at 0.5 MAC, and to 91.4 ± 10.2ml·kg^–1 at 1.0 MAC (0.01 P 0.05). These increases were caused by an increase in the plasma volume.The above data suggests that a concomitant increase in the venous pressure associated with an increase in the intrathoracic pressure produced by positive pressure ventilation would attenuate changes in the CB volume during sevoflurane anesthesia.(Hamada H, Takaori M, Kimura K, et al.: Changes in circulating Blood volume following isoflurane or sevoflurane anesthesia. J Anesth 7: 316–324, 1993)     

自旋回波结合电影MRI在先天性心脏病诊断的初步应用

目的　探讨常规自旋回波 (SE)结合电影MRI对先天性心脏大血管畸形的诊断价值。方法　先天性心脏病患者 2 1例 ,其中Fallot四联症 1 4例 ,房间隔缺损 2例 ,右室双出口 2例 ,单心室 1例 ,主动脉缩窄 2例。所有患者接受MRI检查 ,先做不同层面的SET1 WI,再选择最佳层面做电影MRI。分析MRI检查结果 ,并与超声心动图、心血管造影和手术结果对照。结果　SET1 WI可显示心脏大血管的主要结构畸形 ,电影MRI可进一步明确心血管结构畸形及血液流动改变 ,MRI检查结果与心血管造影及手术结果基本一致。结论　常规SE结合电影MRI能准确显示心脏大血管畸形 ,尤其适用于婴幼儿先天性心脏病的检查。     

Immunotherapeutic targets in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and has a 5-year survival rate of ~20%. Immunotherapies have shown promising results leading to durable responses, however, they are only effective for a subset of patients. To determine the best therapeutic approach, a thorough and in-depth profiling of the tumour microenvironment (TME) is required. The TME is a complex network of cell types that form an interconnected network, promoting tumour cell initiation, growth and dissemination. The stroma, immune cells and endothelial cells that comprise the TME generate a plethora of cytotoxic or cytoprotective signalling pathways. In this review, we discuss immunotherapeutic targets in NSCLC tumours and how the TME may influence patients' response to immunotherapy.     

组织细胞增生症X的影像学特征及鉴别诊断

组织细胞增生症Ｘ其主要病理改变为以单核 巨噬细胞异常增殖和嗜酸性细胞肉芽肿为主要损害。病变骨骼改变比较典型 ,但肺部的病变常无多少特异性 ,易和其他疾病相混淆 ,故对此病作一回顾性分析。１材料与方法病例１ ,男性 ,第１次就诊年龄２８岁 ,以背部酸胀不适及多饮多尿而入院。Ｘ线平片及ＣＴ均发现第５胸椎、右侧附件及局部肋骨破坏 ,术前误诊为转移瘤。手术及病理证实为嗜酸性肉芽肿。３年后第２次以肺部症状和体征为主再次入院治疗。胸片见双肺广泛的斑片状及条索状阴影和网状改变 ,ＭＲＩ示垂体后叶信号降低 ,其内合并有一点状出血…     

Accumulation of L-[2-(F-18)]fluorophenylalanine in peri-infarct area in a patient with acute cerebral infarction

We studied the brain uptake of amino acid in a patient with acute cerebral infarction with L-[2-(F-18)] fluorophenylalanine and positron emission tomography. The increased accumulation of the ligand was specifically found in the peri-infarct area where oxygen metabolism was still maintained but decreased later in the 72-day follow-up period. The kinetic analysis revealed that increased accumulation was not due to increased transport from the blood to the brain but to delayed washout from the brain to the blood. Although the mechanism is still unknown, abnormally high accumulation of L-[F-18]fluorophenylalanine may predict delayed neuronal changes after ischemic insults of the brain.