Immune Checkpoint Inhibitor Toxicities

Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase.     

Sudden Cardiac Death in Patients With Type 1 Versus Type 2 Diabetes

ObjectiveTo investigate the association between type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) with risk of sudden cardiac arrest (SCA).MethodsIn a prospective community-based study of SCA from February 1, 2002, through November 30, 2019, we ascertained 2771 cases age 18 years of age or older and matched them to 8313 controls based on geography, age, sex, and race/ethnicity. We used logistic regression to evaluate the independent association between diabetes, T1D, T2D, and SCA.ResultsPatients had a mean age of 64.5±15.9 years, were 33.3% female and 23.9% non-White race. Overall, 36.7% (n=1016) of cases and 23.8% (n=1981) of controls had diabetes. Among individuals with diabetes, the proportion of T1D was 6.5% (n=66) among cases and 2.0% among controls (n=40). Diabetes was associated with 1.5-times higher odds of SCA. Compared with those without diabetes, the odds ratio and 95% CI for SCA was 4.36 (95% CI, 2.81 to 6.75; P<.001) in T1D and 1.45 (95% CI, 1.30 to 1.63; P<.001) in T2D after multivariable adjustment. Among those with diabetes, the odds of having SCA were 2.41 times higher in T1D than in T2D (95% CI, 1.53 to 3.80; P<.001). Cases of SCA with T1D were more likely to have an unwitnessed arrest, less likely to receive resuscitation, and less likely to survive compared with those with T2D.ConclusionType 1 diabetes was more strongly associated with SCA compared with T2D and had less favorable outcomes following resuscitation. Diabetes type could influence the approach to risk stratification and prevention of SCA.     

凉血通瘀方干预高血压大鼠急性脑出血模型对脑组织中差异miRNA表达的影响＊

目的 研究凉血通瘀方对高血压大鼠急性脑出血模型脑组织miRNA表达的影响，对差异表达的miRNA靶基因进行分析，探索凉血通瘀方可能的药效机制。方法 将自发性高血压大鼠随机分成对照组（B）和实验组（C）。适应性饲养一周后，C组灌胃凉血通瘀方，B组灌胃等体积生理盐水，连续5天，每天1次。构建脑出血模型后收集脑组织，借助全转录组测序技术获得miRNA表达量，与miRBase数据库比对获取已知miRNA，使用miRDeep2预测新miRNA。差异分析软件为DESeq2，筛选阈值为|log₂FC| ≥1 并且P <0.05。对显著差异表达的miRNA进行靶基因预测，对靶基因进行GO功能、KEGG通路富集和PPI网络分析。结果 实验组和对照组对比，共发现21个显著差异表达的miRNA，上调有9个，下调有12个，共预测得到1243个有统计学意义的靶基因。GO富集分析发现，生物过程中突触囊泡分泌的调节、神经递质分泌的调节和神经递质运输的调节占前三位，神经元投射终点、全膜、质膜区域和细胞投射则是主要的细胞成分。分子功能分别为小GTPase绑定、底物特异性跨膜转运蛋白活性和离子跨膜转运体活性。通路分析结果显示，靶基因在癌证通路、pI3K-Akt信号通路、人类乳头瘤病毒感染、神经活性配体-受体相互作用和MAPK通路等分布广泛。采用STRING网站和Cytoscape软件，根据MCC算法筛选出ADRA2C、CASR、CCL28、CCR1、DRD2、GNAT3、GRM2、DYNC1LI1、GABBR1、GNAI1等核心靶基因。结论 凉血通瘀方对脑出血急性期鼠脑组织内miRNA的表达有重要影响；显著差异表达miRNAs可能通过靶向核心基因调控凉血通瘀方干预急性脑出血的病理过程及预后。     

高压氧治疗急性一氧化碳中毒174例护理效果观察

急性CO中毒是我国北方地区冬季的常见病,多发病。若治疗不及时或不彻底又有发生CO中毒迟发性脑病的危险。自从高压氧医学产生和发展以来,目前已成为CO中毒首选的主要治疗手段,取得了很好的治疗效果。本文对近3年来用高压氧(HBO)配合临床药物治疗CO中毒及迟发性脑病174例的治疗护理效果进行了观察,认为对急性CO中毒患者的治疗护理应及早发现、及早就医、及早HBO治疗并坚持足够的疗程,可以提高CO中毒的治愈率,降低死亡率,减少或减轻迟发性脑病的发生,同时认为整个HBO治疗过程中做好每个环节的护理工作是CO中毒患者救治成功的关键。1…     

Primary Prevention of Sudden Cardiac Death: Can We Afford the Cost of Cardioverter-Defibrillators? Data from the Search-MI Registry-Italian Sub-study

Background: Large randomized trials show that in appropriately selected patients with left ventricular dysfunction, implantable cardioverter-defibrillators (ICDs) can improve overall survival at 2–5 years. Since direct implementation of the criteria used in the MADIT II and SCD-HeFT will lead to a marked rise in ICD implants, there is a growing fear that increased use of ICDs may cause a dramatic burden to health care systems. The ICD has traditionally been seen as an expensive form of treatment, which is difficult to accept at the first look. This is mainly due to the nonlinear character of the ICD investment, characterized by high initial expenditure, followed by a deferred pay-off in terms of clinical benefits. Cost-effectiveness analysis may help provide a different perspective on the problem of ICD cost, as may estimation of the daily cost of ICD treatment, assuming a time horizon of 5–7 years—a particularly interesting subject for further registry studies.
Methods and Results: Based on real expenditure data from 2002 to 2005, as recorded in the Search-MI Registry-Italian Sub-study of patients implanted on MADIT II indications, we estimated the daily costs associated with the device and leads. Over a 5–7 year time horizon, the average daily cost was estimated to be €4.60–€6.70. Translation of these figures into U.S. market conditions suggests a daily cost of around $7.90–$11.40.
Conclusions: These findings appear useful to help evaluate the affordability of ICD in comparison with other therapeutic options in a context of limited available economic resources.     

Monolateral hypoplasia of the motor vagal nuclei in a case of sudden infant death syndrome

During the development of motor vagal nuclei (MVN), the neuroblasts of the myeloencephalic basal plate migrate in the dorsolateral direction to form the dorsal motor vagal nucleus (DMVN) and ventrolaterally to form the ventral motor vagal nucleus (VMVN). Those neuroblasts that remain close to the median sulcus will form the hypoglossal nucleus. In support of the congenital origin of the alteration of the MVN in sudden infant death syndrome (SIDS), we report the case of an 8‐month‐old female child who was found dead in her cot. The neuropathological assessment revealed that the medullary triangle of the 4th ventricle floor was asymmetric, owing to the presence of three prominences to the left side of the median sulcus. The medial prominence corresponded to the hypoglossal nucleus, which showed a marked increase in the number of large neurons; the intermediate prominence corresponded to the DMVN whose large neurons were reduced and were recognizable mainly at the level of the medial fringe; the lateral prominence corresponded to the solitary nucleus. The left solitary tract showed a reduction of the transverse diameter. Also, the left VMVN showed marked reduction in the number of neurons. Inflammatory and astrocytic reactions were absent. We suggest that in SIDS cases the hypocellularity of the MVN and the increased number of neurons of the hypoglossal nucleus are intimately related, indicating a congenital alteration due to incomplete migration of the vagal neuroblasts with abnormality of the autonomic cardio‐respiratory control.     

38例非小细胞癌脑转移的综合治疗分析

目的探讨非小细胞肺癌脑转移的有效治疗方案.方法对38例非小细胞肺癌脑转移患者进行头部、胸部放疗并结合全身化疗的综合治疗.结果近期疗效的有效率为76.3%(29/38).神经精神症状缓解率73.7%(28/38),肺部症状缓解率60.5%(23/38).1年生存率31.5%(12/38),2 a生存率10.5%(4/38).结论合理采用综合治疗可有效提高非小细胞肺癌脑转移患者的生存率.     

神经干细胞移植治疗缺氧缺血性脑损伤的实验研究

目的 研究神经干细胞移植治疗缺氧缺血性脑损伤的可行性。方法 取孕龄为12－16天的母鼠，从胎脑中分离神经细胞，进行培养、鉴定。用出生7天的SD大鼠的新生鼠制作缺氧缺血性脑损伤的动物模型，7天后接受神经干细胞移植（移植组，n＝16只），同时设置对照组，只注射磷酸缓冲液（对照组，n=8只），8－10周后，作Y迷宫实验检测大鼠的学习能力和记忆能力。取脑组织作免疫组织化学检查。结果 从大鼠胎脑中成功培养出神经干细胞，培养条件下呈悬浮状态生长，形成神经球，绝大多数的细胞表达神经干细胞的标志物神经巢蛋白（nestin）。接爱神经干细胞移植组大鼠的学习能力、记忆能力和对照组相比，有明显提高，差异具有显著性（P＜0.05）。接受神经干细胞移植大鼠组织中可见存活的移植细胞，并和宿主脑组织融合在一起。结论 在体外培养条件下，可从胎脑组织中培养出神经干细胞，移植到缺氧缺血性脑损伤大鼠脑内后，细胞与宿主的脑组织融合在一起，动物的学习、记忆能力有改善。移植神经干细胞是治疗缺氧缺知性脑损伤的有效方法之一。     

高热惊厥214例临床分析

本文分析了214例高热惊厥,结果为:检出率4.35％;男女之比为1.61:1;好发年龄为6个月～6岁(93.5％);首发年龄为6个月～4岁(89.9％);惊厥发作时体温多在39℃以上(74.6％);惊厥发作多在发热后12h内(72.4％);每次热病中惊厥发作1～3次(99.5％);惊厥持续时间多在15min内(91.0％);致惊厥发作的热性疾病以上呼吸道感染为最多;214例中63例复发,其中2例转癫痫,61例尚未发现智力低下或其他异常。从2例转癫痫的临床及脑电图看,提示惊厥发作愈重,持续时间愈长,转癫痫的可能性愈大。